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This study investigated the trends of nontuberculous mycobacterial (NTM) isolates and the minimal inhibitory concentrations (MIC) of antimicrobial agents in Korea. Data from 2013 to 2019 were collected from 69 medical institutions through 12 branches of the Korean Institute of Tuberculosis. NTM identification was conducted using the Advansure Mycobacteria Genoblot assay. The MIC of antibiotics against NTM species were measured using the broth microdilution method according to the Clinical and Laboratory Standards Institute guidelines. Over seven years, 86,194 NTM identifications were requested, with an annual increase from 8034 in 2013–17,229 in 2019. The most frequently identified NTM species were M. intracellulare (33,467; 47.3%) and M. avium (19,818; 27.2%), followed by M. abscessus (6858; 9.4%) and M. massiliense (3156; 4.3%). Regarding the antimicrobial agents, imipenem exhibited the greatest difference in MIC between M. intracellulare and M. avium , whereas clarithromycin showed the most significant difference between M. abscessus and M. massiliense. No notable changes were observed in the annual MIC distribution of most antibacterial agents, except for clarithromycin in M. abscessus. The prevalence of NTM in Korea is gradually increasing, and follow-up studies on NTM isolates identified as the causative agents of infection are needed. [ABSTRACT FROM AUTHOR]

Seventeen water samples were collected from four different thermal springs in Saudi Arabia. Microbiological assays were used to assess the antibacterial activities of bacterial colonies against antibiotic-resistant and susceptible-bacterial strains, and 16S rRNA gene sequencing was used to identify the genus and species of these antibiotic-producing bacteria. Chromatography and spectroscopy were used to separate the active compounds and help figuring out what their structures were. Four compounds were isolated using bacteria: N -acetyltryptamine (1), isovaleric acid (2), ethyl-4-ethoxybenzoate (3) and phenylacetic acid (4). Compounds 1 , 2 and 4 were produced from Bacillus pumilus and 3 was from Bacillus licheniformis (AH-E1). The outcomes of the minimum inhibitory concentrations (MICs) showed that all pure compounds produced in this work had antibacterial activities against Gram-positive pathogens (between 128 mg/L and 512 mg/L compared to the control) and compound 2 had activity against E. coli. [ABSTRACT FROM AUTHOR]

About 2.3 billion individuals worldwide are still deprived of the amenity of handwashing with antimicrobial agents. The progress of handwashing with antimicrobial agents in Bangladesh is relatively slower than in many developing countries. The objective of this study was to capture the inequality of the prevalence of handwashing with antimicrobial agents and to identify the factors that are potentially contributing to socio-economic inequalities of handwashing practice in Bangladesh. Cross-sectional study. The present study used the nationally representative cross-sectional data from the latest Bangladesh Demographic and Health Survey (BDHS) 2017–18. A total of 19,457 households were included in the analysis of this study. A regression-based decomposition method was applied to assess the socio-economic contributors of inequality. This study showed that only 38% of Bangladeshi households wash their hands with antimicrobial agents while a pro-rich socio-economic inequality was observed. Household's wealth index was responsible for about 46% of the overall inequality of handwashing with antimicrobial agents while the type of place for handwashing variable contributed 38% of total inequalities. Hygienic toilet facilities (12%) and exposure to mass media (7.4%) are other determinants of total inequalities of handwashing with antimicrobial agents. Despite recent declines in attributable mortality, handwashing with antimicrobial agents remains an important determinant of public health problems in many developing countries like Bangladesh. The regular programs aimed at promoting best hand hygiene practices and ensuring the availability of the necessary infrastructure at the community level will be important measures to eliminate this inequality at the population level. [ABSTRACT FROM AUTHOR]

The emergence of antimicrobial resistance within bacterial communities poses formidable challenges to existing therapeutic strategies aimed at mitigating biofilm-mediated infections. Recent advancements in this domain have spurred the development of targeted antimicrobial agents, designed to selectively eradicate the primary etiological agents while preserving the beneficial microbial diversity of the oral cavity. Targeting glucosyltransferases (GTFs), which play crucial roles in dental biofilm formation, offers a precise strategy to inhibit extracellular polysaccharide synthesis without compromising oral microbiota. This review article delves into the intricate mechanisms underlying dental caries, with a specific focus on the role of GTFs, enzymes produced by S. mutans. It further provides an overview of current research on GTF inhibitors, exploring their mechanisms of action, efficacy, and potential applications in clinical practice. Furthermore, it discusses the challenges and opportunities in the development of novel GTF inhibitors, emphasizing the need for innovative approaches to combat biofilm-mediated oral diseases effectively. [ABSTRACT FROM AUTHOR]

The by-products of Mediterranean agriculture that remain after the production of fruit wines, juices and extracts represent a large source of raw materials rich in phenolic compounds. As a contribution to the current state of knowledge, this study investigated the biological activity and phenolic composition of extracts obtained from blackberry, chokeberry and juniper by-products, as well as the interactions of the extracts in mixtures. The total phenolic content of the samples ranged from 44.42 to 250.28 mg gallic acid equivalents (GAE)/g dry extract, with the extracts from blackberry leaves and juniper needles being the highest. The highest concentration of phenolics detected by high performance liquid chromatography (HPLC) was also found in blackberry leaves (41.30 mg/g dry extract), with rutin dominating. The antioxidant activity of the samples, as measured by ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, ranged from 3.4 to 26.8 mM Trolox equivalents (TE), 15.8–58.4 mM TE and 80.1%–91.8%, respectively. Among the extract mixtures, the highest synergistic interaction was observed between blackberry leaves and juniper by-products extracts at 1:2 and 2:1 ratios. The antimicrobial activity of the extracts was tested against Gram-positive and Gram-negative foodborne pathogens and spoilage bacteria, with the lowest minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values against Staphylococcus aureus , Listeria innocua , Bacillus cereus , Campylobacter jejuni , Pseudomonas spp. and Shewanella spp. On the other hand, the antimicrobial activity of blackberry leaf extract in combination with selected phenolic compounds (vanillic acid, catechin, rutin and apigenin) showed no synergy against the tested microorganisms. Overall, the results suggest that the tested by-products extracts could be utilized for the production of natural antioxidants and antimicrobials for further use in the food industry. [ABSTRACT FROM AUTHOR]

The urgent need for antimicrobial agents to combat infections caused by multidrug-resistant bacteria facilitates the exploration of alternative strategies such as photosensitizer (PS)-mediated photoinactivation. However, increasing studies have discovered uncorrelated bactericidal activities among PSs possessing similar photodynamic and pathogen-targeted properties. To optimize the photodynamic therapy (PDT) against infections, we investigated three type-I PSs of D-π-A AIEgens TI, TBI, and TTI. The capacities of reactive oxygen species (ROS) generation of TI, TBI, and TTI did not align with their bactericidal activities. Despite exhibiting the lowest photodynamic efficiency, TI exhibited the highest activities against methicillin-resistant Staphylococcus aureus (MRSA) by impairing the anti-oxidative responses of bacteria. By comparison, TTI, characterized by the strongest ROS production, inactivated intracellular MRSA by potentiating the inflammatory response of macrophages. Unlike TI and TTI, TBI, despite possessing moderate photodynamic activities and inducing ROS accumulation in both MRSA and macrophages, did not exhibit any antibacterial activity. Therefore, relying on the disturbed anti-oxidative metabolism of pathogens or potentiated host immune responses, transient ROS bursts can effectively control bacterial infections. Our study reevaluates the contribution of photodynamic activities of PSs to bacterial elimination and provides new insights into discovering novel antibacterial targets and agents. [Display omitted] [ABSTRACT FROM AUTHOR]

• Euphorbia dendroides ethanolic extract has a protective effect against CCl 4 -induced acute hepatic damage in rats. • Antimicrobial activities were evaluated against Gram-positive, Gram-negative bacteria and fungi. • Cytotoxic activities were evaluated against three human cell lines HepG2, HCT-116 and MCF-7. Euphorbia dendroides can act as a free radical scavenger, so it protects against acute hepatic damage induced by CCl 4 in rats. Also, it increases the Tm of salmon testis DNA from 68 °C to about 81 °C. In addition to that, it has shown good antibacterial effect against S. aureus, E. coli, B. subtilis and antifungal effect against A. niger . Along with showing good anticancer effects against HepG2 cells with IC 50 = 9.5 μg/mL, HCT-116 cells with IC 50 = 13.6 μg/mL and MCF-7 with IC 50 = 20.9 μg/mL. The docking study was carried out to explore how genistein, the main compound isolated from the extract of E. dendroides , binds to both VEGFR-2 and DNA active sites. Additionally, our compound displayed very well in Silico predicted ADMET profile. Genistein has better absorption (92.893) compared to sorafenib (84.731) and doxorubicin (62.37), as well as not showing any hepatotoxic effects. [ABSTRACT FROM AUTHOR]

[Display omitted] This review aimed to identify antimicrobial agents incorporated into dental materials obtained through additive manufacturing and their efficacy. Protocol registration was performed in Open Science Framework (osf.io/sp3xa/) and an electronic search was carried out in the databases PubMed, Science Direct, Embase, Lilacs, and Scopus, up to February 2022, combining the terms ("additive manufacturing" OR "3D printing") AND (antimicrobial). Eligibility criteria included: experimental studies that incorporated 3D printing material with an antimicrobial agent for dental application; that evaluated antimicrobial activity; articles published in peer-reviewed journals and in English. The database search resulted in 1139 references. The manual selection was carried out in 851 studies. Twenty-five articles were selected for full-text reading, of which 8 were included in this review. Polymers were the dental materials most often modified with antimicrobial agents for 3D printing, followed by metal alloy. The antimicrobials used were mainly nanoparticles, metal particles, antifungals, monomers containing quaternary ammonium salt, and antiseptics such as chlorhexidine. The addition of the antimicrobial agents in polymers and alloy for additive manufacturing showed promising efficacy against Candida spp., Gram-positive and Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

In recent years, the biocompatibility and environmental friendliness of xylan-based materials have demonstrated great potential in the field of food packaging and coatings. In this study, the cationized xylan based composite coating (CXC) was developed using a hybrid system of cationic-modified bamboo xylan (CMX) and sodium alginate (SA) combined with thyme oil microcapsules (TM). The optimized CXC-B was composed of 1.27 % TM, 2.42 % CMX (CMX: SA = 3:2), and 96.31 % distilled water. When applied to the surface of a blueberry, the CXC-B treatment extended the ambient storage time of the fruit to 10 days while substantially reducing its morbidity (P < 0.05) and protecting its texture, flavor, and nutritional integrity. The resulting composite coating provides a promising solution to the problem of blueberry perishability during ambient storage. Schematic diagram for the cationization reaction of xlan extracted from bamboo and its use in the making of composite coating to keep blueberries fresh. [Display omitted] • The composite coating has excellent film-forming properties and anti-fungal decay activity. • This method improved the disadvantage of polysaccharide-based materials that are prone to hygroscopicity. • This complex coating effectively reduces the weight loss of blueberries. [ABSTRACT FROM AUTHOR]

[Display omitted] • Broad-spectrum antimicrobial carbonized nanogels (CNGs) from dextran (DEX), and aliphatic amine (ADA) are prepared. • Loading curcumin quantum dots (Cur-QDs) into DEX/ADA-CNGs provides multifunctional properties. • Cur-QDs-DEX/ADA-CNGs show antimicrobial, antioxidative, and anti-inflammatory activities. • The multifunctional CNGs possess efficient suppression of ocular microbial infection and inflammation in endophthalmitis (EO) model. • The biocompatible multifunctional CNGs than traditional antibiotics are more effective in treating EO. Infectious endophthalmitis (EO) is a severe eye condition characterized by inflammation of the eye's internal fluids and tissues, often resulting from infection by bacteria or fungi. Patients with EO typically experience reduced vision, pain, and conjunctival infection. Despite the use of antibiotics, challenges such as inflammation and drug resistance remain. In this work, we have developed dextran/aliphatic diamines carbonized nanogels (DEX/ADA-CNGs) as board-spectrum antimicrobial agents by a one-step mild carbonization procedure. The CNGs exhibit not only antimicrobial properties but also show good drug delivery potential. Curcumin-based carbon quantum dots (Cur-CQDs) as an anti-inflammatory agent are loaded into DEX/ADA-CNGs to form hybrid carbon-in-carbon nanocomposites (Cur-CQDs@DEX/ADA-CNGs), showing combined antimicrobial, antioxidative, and anti-inflammatory activities. Impressively, CQDs@DEX/ADA-CNGs maintain strong antibacterial effectiveness against drug-resistant strains, with minimum inhibitory concentrations below 110 µg mL−1. The Cur-CQDs@DEX/ADA-CNGs have demonstrated high biocompatibility both in vitro and in vivo. In a rat model of EO, they rapidly (less than 5 days) reduce microbial infection and inflammation in the eye. Given these promising results, Cur-CQDs@DEX/ADA-CNGs show great potential as an enduring intravitreal treatment option for infectious EO. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has necessitated the incorporation of self-disinfectant properties into construction materials, particularly concrete, to mitigate the risks of pathogen transmission during health crises. From 2000 to 2020, over 60 scholarly publications featured the phrase 'antimicrobial concrete,' which showed the growing concerns for future needs. While some studies have investigated antimicrobial concrete (AMC) properties in specific applications, a comprehensive exploration of concrete's antimicrobial characteristics for developing self-cleansing buildings remains limited. The existing research in this area primarily addresses specific issues, leaving a knowledge gap on how AMCs can effectively enhance self-disinfection during health crises. This review aims to fill this gap by thoroughly assessing the current knowledge on potential applications of AMC and their suitability in diverse post-COVID era contexts. The study extensively examines the effects of antimicrobial agents (AMAs) from organic and inorganic sources on microorganisms, evaluating their benefits and limitations when incorporated into concrete. Moreover, it also assesses how these agents influence concrete's rheological and mechanical characteristics. Findings reveal challenges in formulating efficient AMCs, such as the exorbitant cost of inorganic AMAs, which can range from $500 to $5000 per kg, as well as health apprehensions among end-users and the absence of regulatory frameworks. Using AMAs from organic sources, perceived as easily accessible, cost-effective, and less hazardous, can mitigate these challenges. Furthermore, the review outlines future research considerations for effective AMC development. This scholarly contribution advances knowledge on safer and more resilient construction materials, explicitly addressing future public health issues. [Display omitted] [ABSTRACT FROM AUTHOR]

This study investigates the antimicrobial, antibiofilm, antioxidant, and cytotoxic properties of methanolic extracts of Neowestiellopsis persica (Nwp) and Desmonostoc sp. (Dns), for the first time and the preliminary identification of possible compounds in these extracts by measurement of total phenolic content, TLC-bioautography, HPLC and GC-Mass analysis. The results showed that the two selected extracts have a moderate to good MIC range (3.9 to 125μg/mL) exclusively against standard and clinical staphylococci. MTT assay showed that Nwp and Dns inhibited CHO cells with the IC 50 of 338.94 and 209.90 μg/mL. Also, Nwp was a more potent antioxidant than Dns. Although both extracts' antimicrobial properties were very similar, Nwp was chosen for identification analysis due to its antioxidant properties, higher extract production rate, and lower cytotoxicity. The TLC-recovered antimicrobial fraction (Nwp-derived compounds) in HPLC showed a sharp peak (retention time = of 1.855 min) that its analysis by GC-Mass introduced a unique and different derivative of phthalate, which is similar to Diisooctyl Phthalate and Bis (2-ethylhexyl) phthalate. As a novelty, this study reports a derivative of phthalate from a Neowestiellopsis persica for the first time, which, along with exclusive antimicrobial properties against staphylococci and acceptable toxicity, has good antioxidant properties that can be introduced as a promising candidate for further in vitro and in vivo studies. However, more chemical and structural analyses such as high resolution mass spectrometry (HR-MS) and Nuclear Magnetic Resonance (NMR) are recommended for a better understanding of the nature of this substance. • Neowestiellopsis persica has similar antimicrobial and anti-biofilm effects. • N. persica produces a new phthalate derivative. • New phthalate is exclusively active against staphylococci strains. • New phthalate was similar to compounds diisooctyl phthalate and Bis(2-ethylhexyl) phthalate. • N. persica extract is a good antioxidant agent. [ABSTRACT FROM AUTHOR]

[Display omitted] • The search for effective drugs to treat new and existing diseases is a laborious one requiring a large investment of capital, resources, and time. • The COVID-19 pandemic has been a painful reminder of the lack of development of new antimicrobial agents to treat emerging infectious diseases. • Artificial intelligence (AI) and other in silico techniques can drive a more efficient, cost-friendly approach to drug discovery. • AI techniques will pave the way towards targeted approaches for identifying lead candidates. The search for effective drugs to treat new and existing diseases is a laborious one requiring a large investment of capital, resources, and time. The coronavirus 2019 (COVID-19) pandemic has been a painful reminder of the lack of development of new antimicrobial agents to treat emerging infectious diseases. Artificial intelligence (AI) and other in silico techniques can drive a more efficient, cost-friendly approach to drug discovery by helping move potential candidates with better clinical tolerance forward in the pipeline. Several research teams have developed successful AI platforms for hit identification, lead generation, and lead optimization. In this review, we investigate the technologies at the forefront of spearheading an AI revolution in drug discovery and pharmaceutical sciences. [ABSTRACT FROM AUTHOR]

Teaching and learning the spectrum of activity (SOA) of antimicrobial agents can be a challenge in pharmacy education. This study describes the implementation and assessment of a novel tool to aid in the instruction of SOA. Physical manipulatives were used as an active-learning technique to model bacterial pathogens for antimicrobial SOA in an infectious diseases (ID) integrated medication therapy management course. Pharmacy students enrolled in two consecutive years of the ID course were provided the opportunity to utilize a set of manipulatives for in-class activities and out-of-class practice. The manipulatives were small, colored building blocks that could be used to model bacterial pathogens for antimicrobial SOA. A key was included with each set of blocks, color-coding each block to represent a different bacterial pathogen or pathogen group. Blocks were used during classroom instruction to model the SOA of antimicrobial agents, compare/contrast SOA between medications, and model bacterial pathogens requiring empiric coverage for various infections, allowing students to produce "bug-drug" matches. Course data from the previous year was utilized to compare pre-implementation aggregate performance with post-implementation data. Performance on SOA-related questions was assessed during the course, using an independent samples t -test. The intervention group exhibited a statistically significant increased mean score on test questions relating to SOA as compared to the control group. The use of manipulatives was associated with improved performance on SOA-related questions in an integrated ID course of pharmacy students. [ABSTRACT FROM AUTHOR]

Over time, the knowledge on the role of histones has significantly changed. Initially, histones were only known as DNA packaging proteins but later, it was discovered that they act extracellularly as powerful antimicrobial agents and also as potentially self-detrimental agents. Indeed, histones were found to be the most abundant proteins within neutrophil extracellular traps what ultimately highlighted their microbicidal function. In addition, extracellular histones proved to be involved in triggering exacerbated inflammatory and coagulation responses, depending on the cell type affected. Consequently, several investigations were conducted towards studying the potential of histones and their derivatives as either biomarkers or therapeutic target candidates in different diseases in which inflammation and thrombosis have a key pathophysiological role, such as sepsis, thrombosis and different types of cancer. The main objective of this review is to summarize and discuss the current state of the art with regard to both beneficial and harmful roles of histones and also their possible use as biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

A green and scalable approach for the preparation of few-layered graphene utilizing the biowaste of potato peels has been developed. The potato peels have been dried and carbonized to obtain a new graphite structure that has been exfoliated in N -methylene phosphonic acid chitosan (MPC). The exfoliation process assisted the formation of graphene sheets with a high size diameter and quality of 50% based on the weight of graphite structure. The graphene sheets were green decorated with silver nanoparticles using microwave power to obtain new nanocomposites. The mass ratio between the graphite and silver nitrate was optimized and observed to change the morphology and size diameter of silver nanoparticles. The as-prepared MPC structure, graphene, and silver decorated graphene nanocomposites were characterized using 1HNMR, FTIR, XRD, UV/Vis spectrophotometer, SEM, and TEM besides tested as antimicrobial agents. The bacterial performance was also controlled by changing the number of AgNPs distributed on graphene sheets based on the mass ratios of graphite/AgNO 3. The inhibition diameter of silver decorated graphene was considerably increased to 24.8, and 20.1 mm as in the case of MPC-GRP-Ag30 composite compared to the pure graphene (11.2, 13.5 mm) for E. coli and S. aureus , consecutively proposing that the blade edge of graphene sheets can destroy the bacteria membrane and release silver cations promptly that are directed for the interaction with the cytoplasmic parts of the bacteria cell. Such findings offer green and biocompatible antibacterial agents based on the graphene derived from the biowaste products. [ABSTRACT FROM AUTHOR]

Biopolymers, as chitosan and alginate, have gained prominence in the biomedical area, mainly for application in wound dressings, as partial replacements for synthetic polymers. The present work aimed to compare the influence of the antimicrobial agent incorporation form on the properties of films prepared by casting. The chitosan/alginate-based films were manufactured containing oregano essential oil (OEO) or ground oregano leaves (OR). The OEO was chosen due to its excellent pharmacological properties, and the substitution by OR can represent an advantageous alternative for minimizing the final cost of the product, by removing the oil extraction step. The films, with different amounts of OEO and OR, were characterized in terms of their morphological, physicochemical, mechanical and antimicrobial properties. The films had properties according to desirable for wound dressing application: water vapor flux less than 35 g m−2 h−1, moderate liquid absorption capacity, and similar mechanical properties to human skin. All developed films showed antimicrobial activity against the bacteria Escherichia coli and Staphylococcus aureus. Formulations containing OEO presented the largest inhibition zones, although OR showed high potential for the proposed use. These results suggest that films developed, with both OEO and ground oregano leaves, are promising for use as dressings. [Display omitted] [ABSTRACT FROM AUTHOR]

The aptitude of Mycoplasma gallisepticum (MG) for changing its surface proteins allows the pathogen to reduce the efficacy of antimicrobial agents, especially those targeting surface proteins. Although antibiotic treatment cannot be a solution for the eradication of avian mycoplasmosis, it can be considered a good option to minimize the number of deaths. One of the challenges of antibiotic treatments is the development of antimicrobial resistance (AMR) among field isolates. Monitoring the antimicrobial susceptibility profile of field isolates can be a practical way of avoiding AMR. Thus, various tests have been developed to determine the antimicrobial susceptibility profile of field isolates. A modified broth microdilution minimum inhibitory concentration (MIC) test has been regularly used to measure the antimicrobial susceptibility profile of MG field isolates. Numerous studies have reported an increase in the number of antibiotic-resistant field isolates of MG. Therefore, this study presents a systematic review on antimicrobial MIC values of MG isolates to gather recent knowledge and investigate the prevalence and distribution of AMR among MG field isolates. A thorough search was conducted for related studies throughout 3 electronic databases. Altogether, 23 studies were identified as eligible studies and were used for further analysis. The results showed that enrofloxacin, oxytetracycline, and tylosin had the highest number of resistant isolates in most of the geographical distributions, respectively. Minimum inhibitory concentrations of these antibiotics need to be determined regularly to optimize treatment dosages. [ABSTRACT FROM AUTHOR]

Nocardiopsis dassonvillei prevails under harsh environmental conditions and the purpose of this review is to highlight its biological features and recent biotechnological applications. The organism prevails in salt-rich soils/marine systems and some strains endure extreme temperatures and pH. A few isolates are associated with marine organisms and others cause human diseases. Comparative genomic analysis indicates its versatility in producing biotechnologically relevant metabolites. Antimicrobial, cytotoxic, anticancer and growth promoting biomolecules are obtained from this organism. It also synthesizes biotechnologically important enzymes. Bioactive compounds and enzymes obtained from this actinomycete provide evidence regarding its metabolic competence and its potential economic value. [ABSTRACT FROM AUTHOR]

• The quality of CPGs for CRGNB treatment was heterogeneous among different domains. • The highest domain score of methodological quality was for 'clarity of presentation'. • The quality of 'stakeholder involvement' and 'applicability' domains were suboptimal. • The overall reporting quality was imperfect, with proportions between 45.7 and 85.7%. • Both monotherapy with novel drugs and combination therapy are important strategies. This study aimed to appraise clinical practice guidelines (CPGs) for the treatment of carbapenem-resistant Gram-negative Bacilli (CRGNB) infections and to summarise the recommendations. A systematic search of the literature published from January 2012 to March 2023 was undertaken to identify CPGs related to CRGNB infections treatment. The methodological and reporting quality of eligible CPGs were assessed using six domains of the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and seven domains of the Reporting Items for practice Guidelines in HealThcare (RIGHT) checklist. Basic information and recommendations of included CPGs were extracted and compared. A total of 21 CPGs from 7953 relevant articles were included. The mean overall AGREE II score was 62.7%, and was highest for "clarity of presentation" (90.2%) and lowest for "stakeholder involvement" (44.8%). The overall reporting quality of all of the CPGs was suboptimal, with the proportion of eligible items ranging from 45.7 to 85.7%. The treatment of CRGNB infections is related to the type of pathogen, the sensitivity of antimicrobial agents, and the site of infection. In general, the recommended options mainly included novel β-lactam/ β-lactamase inhibitors, cefiderocol, ampicillin-sulbactam (mainly for carbapenem-resistant Acinetobacter baumannii [CRAB]), and combination therapy, involving polymyxin B/colistin, tigecycline (except for carbapenem-resistant Pseudomonas aeruginosa), aminoglycosides, carbapenems, fosfomycin, and sulbactam (mainly for CRAB). The methodological and reporting quality of CPGs for the treatment of CRGNB infections are generally suboptimal and need further improvement. Both monotherapy with novel drugs and combination therapy play important roles in the treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Bacillus cereus is a prevalent foodborne pathogen that induces food poisoning symptoms such as vomiting and diarrhea. Its capacity to form spores and biofilm enables it to withstand disinfectants and antimicrobials, leading to persistent contamination during food processing. Consequently, it is necessary to develop novel and efficient antimicrobial agents to control B. cereus , its spores, and biofilms. Peptidoglycan hydrolases have emerged as a promising and eco-friendly alternative owing to their specific lytic activity against pathogenic bacteria. Here, we identified and characterized a Lysozyme-like cell wall hydrolase Lys14579, from the genome of B. cereus ATCC 14579. Recombinant Lys14579 specifically lysed B. cereus without affecting other bacteria. Lys14579 exhibited strong lytic activity against B. cereus , effectively lysing B. cereus cell within 20 min at low concentration (10 μg/mL). It also inhibited the germination of B. cereus spores and prevented biofilm formation at 12.5 μg/mL. Moreover, Lys14579 displayed good antimicrobial stability with negligible hemolysis in mouse red blood cells and no cytotoxicity against RAW264.7 cells. Notably, Lys14579 effectively inhibited B. cereus in boiled rice and minced meat in a dose-dependent manner. Furthermore, bioinformatics analysis and point mutagenesis experiments revealed that Glu-47 was the catalytic site, and Asp-57, Gln-60, Ser-61 and Glu-63 were active-site residues related with the cell wall lytic activity. Taken together, Lys14579 could be a promising biocontrol agent against vegetative cells, spores, and biofilm of B. cereus in food industry. [Display omitted] • A cell wall hydrolase, named Lys14579, was characterized from the genome of B. cereus diarrheal reference strain. • Lys14579 showed strong and rapid antimicrobial activity against B. cereus. • Lys14579 could effectively inhibit B. cereus spore germination and biofilm formation at 12.5 μg/mL. • The activity of Lys14579 remained stable under a wide range of pH values, NaCl concentrations, and temperature treatments. • Lys14579 may be useful antimicrobial agent against B. cereus in cooked rice and minced meat. [ABSTRACT FROM AUTHOR]

• Thirteen new poly-heterocyclic compounds have been synthesized. • AIM and DFT methods were applied to get insights into their molecular structures, electronic properties and chemical reactivity. • 4a-4f incorporating a quinoline unit were found to be promising antimicrobial agents against S. typhimurium and B. subtilis. • 4a-4f exhibit excellent affinity for the active site of DNA gyrase. The increasing threat of antibiotic resistance has led to a pressing need for the development of new antimicrobial agents. Nitrogen-containing heterocycles are widely used in the development of drugs due to their broad spectrum of pharmacological activities, including antimicrobial properties. In this study, a series of 13 hybrid molecules containing two to four nitrogen heterocycles were designed using the molecular hybridization approach. The synthesized compounds were characterized and their antimicrobial properties were examined against two bacterial strains and a Candida strain. The most promising compounds were found to be those bearing the quinoline unit, exhibiting a MIC of less than 31.25 μg/mL against S. typhimurium and Bacillus subtilis. Molecular docking studies revealed that these compounds have excellent affinity with the DNA gyrase enzyme, making them potential candidates for further development as antimicrobial agents. [Display omitted] [ABSTRACT FROM AUTHOR]

The food industry is developing natural antimicrobial materials for food preservation applications in response to the increasing demand for more sustainable and environmentally friendly consumer products. In particular, there is interest in the creation of natural antimicrobial packaging materials to enhance the safety and extend the shelf-life of foods. However, the production of these materials is often challenging because of their low stability during food processing and storage, their interactions with components in foods, and the uncontrolled release of encapsulated active components during storage. Some of these limitations can be overcome by using electrospun antimicrobial hybrid mats, in which natural antimicrobials are trapped within nanofibers fabricated by electrospinning. This review summarizes the principles underlying the formation and application of innovative materials consisting of natural antimicrobials encapsulated within nanofiber structures produced by electrospinning. In particular, the application of these nanocomposite materials to a number of important food groups are critically discussed, including meat, dairy, fruit, and vegetable products. Electrospinning is an effective, straightforward, and cost-effective method to produce fibers with high porosity and surface-to-volume ratio which impede the primary fast release of entrapped compounds and provide their controlled release into the food system. Hence, according to these structural advantages, loading bioactive compounds into electrospun fibers improves their functionality, stability, bioavailability, and controlled release, which makes them a favorable option to be used in several applications including food packaging. [Display omitted] Natural antimicrobials can be encapsulated in nanofibers produced by electrospinning. • Electrospun fibers can control the release of entrapped antimicrobials into foods. • Loading antimicrobials into electrospun fibers improves their functionality and stability. • Electrospinning is an efficient method of creating active packaging materials. [ABSTRACT FROM AUTHOR]

The agricultural food products industry in Bangladesh depends on utilizing antimicrobials indiscriminately as growth promoters and for controlling infectious diseases. Thus, there is always a risk of antimicrobial agent accumulation in food sources that originate from agricultural production. In the present study, we collected data from published articles between January, 2013 and December, 2019 on antimicrobial residues in human food sources such as meat, milk, eggs, and fishes. Liver contained the highest percentage of antimicrobial residues (74%; 95% CI: 59.66–85.37) against the in vitro enteric pathogen Escherichia coli in layer chickens. Similar results were demonstrated in liver (68%; 95% CI: 53.30–80.48) and kidney (66%, 95% CI: 51.23–78.79) of layer chickens against Bacillus cereus and Bacillus subtilis. Amongst all antibiotics, the highest concentrations of ciprofloxacin were detected in kidney (48.57%; 95% CI: 31.38–66.01), followed by liver (47.56; 95% CI: 40.88–54.30) of broiler chickens. Ciprofloxacin was also present in liver (46.15%; 95% CI: 33.70–58.96) of layer chickens. The percentage of ciprofloxacin in thigh and breast meat in broiler bird were 41.54% (95% CI: 34.54–48.79) and 37.95% (95% CI: 31.11–45.15) respectively. Enrofloxacin was the second most dominant antimicrobial agent and was present in the liver of both types of poultry (Broiler and Layer chickens: 41.54%; 95% CI: 29.44–54.4 and 437.33%; 95% CI: 30.99–44.01). The prevalence rates of enrofloxacin in thigh and breast meat of broiler chickens were 24.10% (95% CI: 18.28–30.73) and 20.51% (95% CI: 15.08–26.87), respectively. Tetracycline, a commonly used antibiotic in livestock, was present in the liver (49.23%; 95% CI: 36.60–61.93) of layer chickens. In case of aquaculture food products, the highest amount of amoxicillin (683.2 mg/kg) was detected in Tilapia fish (Oreochromis niloticus), followed by 584.4 mg/kg in climbing perch (Anabas testudineus) and 555.6 mg/kg in Rui fish (Labeo rohita). Among the five types of fishes, Rui fish (0.000515 mg/kg) contained the highest concentrations of chloramphenicol antibiotic residues. The presence of antimicrobial residues in meat, milk, egg, and fish is a serious public health threat due to the potential induction of antimicrobial resistance. It can negatively impact the food supply chain, especially with the current strain that it is already facing with the current COVID-19 pandemic. The findings of the present study highlight the ongoing risk of residual antimicrobial agents in food of animal origin in Bangladesh and countries with similar practices. This can draw the attention of public health officials to propose plans to mitigate or stop this practice. • The indiscriminate use of antimicrobials leads to its accumulation in food sources. • The birds' liver/kidney had antimicrobials resistant to E coli, B cereus & B subtilis. • Residual antimicrobials in birds' organs include ciprofloxacin and enrofloxacin. • Residual antibiotics in fish include amoxicillin in Tilapia & chloramphenicol in Rui. • Antimicrobial residues in meat, milk, egg & fish can induce antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Metal-based drugs can modulate various biological processes and exhibit a rich variety of properties that foster their use in biomedicine and chemical biology. On the way to intracellular targets, ligand exchange and redox reactions can take place, thus making metallodrug speciation in vivo a challenging task. Advances in NMR spectroscopy have made it possible to move from solution to live-cell studies and elucidate the transport of metallodrugs and interactions with macromolecular targets in a physiological setting. In turn, the electronic properties and supramolecular chemistry of metal complexes can be exploited to characterize drug delivery nanosystems by NMR. The recent evolution of in-cell NMR methodology is presented with special emphasis on metal-related processes. Applications to paradigmatic cases of platinum and gold drugs are highlighted. [Display omitted] • Metallodrugs are used as anticancer, antimicrobial, and contrast agents. • NMR spectroscopy can probe metallodrug speciation in body fluids and live cells. • In-cell NMR studies reveal metallodrug modulation of metal- and redox processes. • Combined with multi-omics and computational tools, NMR aids target validation. • NMR can speed up the drug discovery process and help devise new drug formulations. [ABSTRACT FROM AUTHOR]

Global antimicrobial crisis and advent of drug resistant fungal strains has substantially distressed disease management for clinicians. Biodegradable silver nanoparticles (AgNps) emerge as an excellent alternative remedial option. In the current study, the anti-biofilm activity of microwave irradiated kappa-carrageenan (CRG) capped AgNps against Candida albicans , and Candida glabrata was investigated in terms of their effect on reactive oxygen species (ROS) generation, cellular morphology, biochemical composition, and the activity of enzymes of extracellular matrix. Minimum inhibitory concentration and fungicidal concentration value of CRG-AgNps against both Candida spp. ranged between 400 and 500 μg/mL. The 80% of Candida biofilm was inhibited and eradicated by CRG-AgNps at a concentration of ~300 μg/mL. Microscopic studies indicate that CRG-AgNps caused morphological damage through membrane disruption and pore formation. Further, CRG-AgNps generated ROS in a concentration-dependent manner and modulated the composition of Candida biofilm ECM by increasing the carbohydrate and eDNA content. CRG-AgNps also significantly inactivated the hydrolytic enzymes, thus hindering the biofilm forming ability. In conclusion, all these results suggest that the CRG-AgNps are potential antifungal agents against Candida biofilms, and they inhibit/eradicate the fungal biofilms through multiple signalling mechanisms. Unlabelled Image • CRG-AgNp have successfully eradicated preformed fungal biofilm. • CRG-AgNp generates ROS and inactivates hydrolytic enzymes. • CRG-AgNp inhibited biosynthesis of ECM components. [ABSTRACT FROM AUTHOR]

In the present study, chitosan-zinc oxide (CS-ZnO) nanocomposite with/without gentamicin was synthesized and characterized which used as an antibiofilm agent to inhibit the biofilm formation of Pseudomonas aeruginosa (P. aeruginosa) PAO1 and Staphylococcus aureus (S. aureus). Synthesized CS-ZnO nanocomposite was characterized with the DLS (Dynamic Light Scattering), FTIR (Fourier Transform Infrared), XRD (X-ray Diffraction) and SEM (Scanning Electron Microscope). The minimum inhibitory concentrations (MICs) against P. aeruginosa PAO1 and S. aureus determined using broth microdilution methods. The influence of sub-MIC (1/4 MIC) and MIC concentration of CS-ZnO nanocomposite and gentamicin alone and in combination on biofilm formation was also determined. A four-fold MIC reduction in S. aureus and P. aeruginosa PAO1 treated by the gentamicin loaded CS-ZnO nanocomposite, and 84% reduction of biofilm formation for P. aeruginosa PAO1 and 77% reduction of biofilm formation for S. aureus , was observed compared to the gentamicin alone (P < 0.05). This study showed the important role of nanocomposite in designing novel antibacterial and antibiofilm agents to combat the P. aeruginosa and S. aureus biofilm-related infections. [ABSTRACT FROM AUTHOR]

This review aimed to provide a critical appraisal of alternative antimicrobial strategies in lieu of traditional triple antibiotic paste (TAP). This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The literature search was performed in 8 databases (PubMed/Medline, Embase, LILACS, Web of Science, Scopus, BVS, SciELO, and the Cochrane Library), selecting clinical, in vitro , in vivo , and in situ studies that evaluated antimicrobial alternatives to TAP in regenerative endodontics. Studies lacking an experimental TAP group were excluded. A total of 1705 potentially relevant records were initially identified. From the 38 studies retrieved for full-text reading, 16 fulfilled all selection criteria and were included in the qualitative analysis. According to the study design, 11 studies were solely in vitro , 1 study was both in vitro and in vivo (animal model), 2 studies were solely animal experiments, and 2 studies were clinical trials. The alternative antimicrobial agents to TAP consisted of modified TAP formulations (eg, a combination of TAP with chitosan); TAP-eluting nanofibers; propolis; chlorhexidine (CHX) gels/solutions; double antibiotic pastes composed of distinct combinations of antibiotics; Ca(OH) 2 -based formulations; and sodium hypochlorite. Overall, most of the alternative agents performed similarly to TAP, although some strategies (eg, Ca(OH) 2 - and CHX-based formulations) seemed to present dubious importance in the control of infection. TAP still remains an excellent option in terms of the complete elimination of microorganisms. This review points to the use of electrospun fibers as a drug delivery system to offer a controlled release of the antimicrobial agent, as well as the use of natural compounds, deserving future investigation. [ABSTRACT FROM AUTHOR]

The prevalence and diversity of Staphylococcus species from wild European rabbits (Oryctolagus cuniculus) in the Azores were investigated, and the antibiotic resistance phenotype and genotype of the isolates were determined. Nasal samples from 77 wild European rabbits from São Jorge and São Miguel islands in Azores were examined. Antibiotic susceptibility of the isolates was determined using the Kirby-Bauer disk diffusion method, and the presence of antimicrobial resistance genes and virulence factors was determined by PCR. The genetic lineages of S. aureus isolates were characterized by spa typing and multilocus sequence typing. A total of 49 staphylococci were obtained from 35 of the 77 wild rabbits. Both coagulase-positive (8.2%) and coagulase-negative (91.8%) staphylococci were detected: 4 S. aureus, 17 S. fleurettii, 13 S. sciuri, 7 S. xylosus, 4 S. epidermidis, and 1 each of S. simulans, S. saprophyticus, S. succinus, and S. equorum. The four S. aureus isolates showed methicillin susceptibility and were characterized as spa type t272/CC121, Panton-Valentine leukocidin negative, and hlB positive. Most of the coagulase-negative staphylococci showed resistance to fusidic acid and beta-lactams, and multidrug resistance was identified especially among S. epidermidis isolates. The mecA gene was detected in 20 isolates of the species S. fleurettii and S. epidermidis, associated with the blaZ gene in one S. epidermidis isolate. Five antimicrobial resistance genes were detected in one S. epidermidis isolate (mecA,dfrA,dfrG,aac6′-aph2′′, and ant4). Our results highlight that wild rabbits are reservoirs or "temporary hosts" of Staphylococcus species with zoonotic potential, some of them carrying relevant antimicrobial resistances. Staphylococci are frequently detected in nasal samples of wild rabbits. Main Staphylococcus spp. (of 9 detected): fleurettii, sciuri, xylosus, epidermidis, and aureus. All S. aureus were MSSA and typed as t272/CC121. The mecA gene was detected in 44% of CoNS; all were of S. epidermidis or S. fleurettii species. Fusidic acid resistance is detected in most of CoNS, and multidrug resistance in S. epidermidis. [ABSTRACT FROM AUTHOR]

Bacterial cells adopt various strategies to adapt themselves in diverse environmental conditions. Salmonella is one such bacteria with diverse mechanisms to survive, replicate and infect in wide host range. This study aims at investigating the biofilm-forming ability of multidrug-resistant and sensitive Salmonella serovars on exposure to bile. Antibiogram of all the isolates was determined by disk diffusion method and their biofilm-forming ability in the presence or absence of bile was assessed by microtiter plate assay. Biofilm results were validated by calcofluor, Congo red plate and test tube method. Few isolates were selected for further study of their expression of biofilm related genes on exposure to bile using real time PCR. Among the 59 isolates of Salmonella isolated from seafood and poultry, 30 isolates were multi-drug resistant (MDR). Under control conditions, 57% (n = 25) of the serovars were able to form biofilm. While, 86% (n = 51) of the serovars produced biofilm in the presence of bile. The relative gene expression study of the selected serovars for 8 different genes showed a striking difference in the expression levels, supporting the hypothesis that the presence of bile triggers biofilm formation in food associated strains of non-typhoidal Salmonella by upregulation of genes involved in biofilm production. [ABSTRACT FROM AUTHOR]

The enterococci are ubiquitous bacteria able to colonize the human and animal gastrointestinal tracts and fresh and fermented food products. Their highly plastic genome allows Enterococcus spp. to gain resistance to multiple antibiotics, making infections with these organisms difficult to treat. Food-borne enterococci could be carriers of antibiotic resistance determinants. The goal of this work was to study the characteristics of Enterococcus spp. in fermented milk products from Poland and their antibiotic resistance gene profiles. A total of 189 strains were isolated from 182 dairy products out of 320 samples tested. The predominant species were Enterococcus faecium (53.4%) and Enterococcus faecalis (34.4%). Isolates were resistant to streptomycin (29.1%), erythromycin (14.3%), tetracycline (11.6%), rifampicin (8.7%), and tigecycline (8.1%). We also detected 2 vancomycin-resistant and 3 linezolid-resistant strains; however, no vanA or vanB genes were identified. A total of 57 high-level aminoglycoside resistance strains (30.2%) were identified, most of which have the ant(6′)-Ia gene, followed by the aac(6′)-Ie-aph(2″)-Ia and aph(3″)-IIIa genes. Resistance to tetracycline was most often conferred by tetM and tetL genes. Macrolide resistance was most frequently encoded by ermB and ermA genes. Conjugative mobile genetic element (transposon Tn 916– Tn 1545) was identified in 15.3% of the strains, including 96.3% of strains harboring the tetM gene. This study found that enterococci are widely present in retail ready-to-eat dairy products in Poland. Many isolated strains are antibiotic resistant and carry transferable resistance genes, which represent a potential source of transmission of multidrug-resistant bacteria to humans. [ABSTRACT FROM AUTHOR]

Recently, the structural and behavioral changes of microorganisms have been rapidly increased. The appearance of resistant bacteria by enhancing antibiotic adaptation potentially is a significant concern for public health; thus, many efforts are needed to promote efficiency of antimicrobial substances. Surface functionalization of antimicrobial nanoparticles can improve their efficiency and diverse studies have shown their high potentials against resistant bacteria. The main objective of this study was to present an overview of the effect of surface functionalization of nanoparticles on their antimicrobial activities against resistant bacteria and discuss different types of functionalization methods for improving nanoparticle functions. The common functional compounds which can be applied on the surface of antimicrobial nanoparticle are described and the current application of functionalized nanoparticles in controlling high resistant bacteria are summarized and tabulated. The surface functionalization of nanoparticles is an effective method in inhibition of the growth of various bacteria. Cationic polymers, small ligands, and biomolecules are the most popular functional compounds which have been successfully applied for improving the antimicrobial activities of nanoparticles through bonding with their surfaces. The changes in the surface characteristics of nanoparticles such as charge, shape, release behavior, and synergistic effects of functional agents on the nanoparticles can greatly enhance their antimicrobial efficiencies. Surface-functionalized antimicrobial nanoparticles with different functional compounds. Image 1 • Efficient antimicrobial systems are needed to overcome antibiotic resistance of pathogenic bacteria. • Surface functionalization of nanoparticles enhances their antimicrobial activities. • Cationic polymers, ligands, and biomolecules are effective surface functional compounds. • Binding and attachment are the main methods for surface-functionalization of nanoparticles. [ABSTRACT FROM AUTHOR]

Seed-borne fungus Penicillium duclauxii was examined in this study to investigate its capability of synthesizing silver nanoparticles (Ag-NPs). In vitro experiments were conducted using corn-grain contaminating fungal isolate. Ag-NPs detection and characterization were assayed by the aid of spectroscopic techniques. Spectroscopy (energy dispersive), X-ray diffraction, transmission electron-microscope and optical absorption dimensions were employed. Ag-NPs with biosynthesized were used to test invitro against Bipolaris sorghicola ; the cause of target leaf spot disease on sorghum plants. The myco-synthesis of Ag NPs using Penicillium duclauxii was proved in this study. Moreover, Bipolaris sorghicola was successfully inhibited by such Ag NPs in vitro. [ABSTRACT FROM AUTHOR]

Background: It has not been investigated whether the quick sepsis-related organ failure assessment score (qSOFA), a new bedside tool for early sepsis detection, may help accelerating antibiotic initiation in ED patients with sepsis.Methods: In this prospective pre/post quasi-experimental single-ED study, patients admitted with a suspected bacterial infection were managed using standard triage procedures only (baseline) or in association with qSOFA (intervention, with prioritization of patients with a qSOFA ≥ 2).Results: A total of 151/328 (46.0%) and 185/350 (52.8%) patients with definite bacterial infection met the criteria for sepsis in the baseline and intervention periods, respectively. The sensitivity and specificity of a qSOFA ≥ 2 for sepsis prediction were 17.3% (95% confidence interval [CI], 13.6%-21.7%) and 98.8% (95% CI, 97.0%-99.5%). Eleven (7.3%) and 28 (13.5%) patients with sepsis in the baseline and intervention periods received a first antibiotic dose within one hour following triage (primary endpoint, absolute difference 6.2%, 95% CI [-0.5%, 12.7%], P = 0.08). The proportions of patients with sepsis receiving a first antibiotic dose within three hours following triage (39.7% [50/151] versus 36.8% [68/185], absolute difference - 2.9%, 95% CI [-13.3%, 7.3%], P = 0.65), requiring ICU admission, or dying in the hospital were similar in both periods. The median ED occupation rate at triage was 104.3% (interquartile range [IQR], 80.4%-128.3%), with a median number of 157 ED visits per day (IQR, 147-169).Conclusions: A qSOFA-based triage procedure does not improve antibiotic timing and outcomes in patients with sepsis admitted to a high-volume ED. The qSOFA value at triage was poorly sensitive for early sepsis detection. Trial registration (ClinicalTrials.gov): NCT03299894. [ABSTRACT FROM AUTHOR]

Objective: Antibiotics change the composition of the intestinal microbiota. The magnitude of the effect of antibiotics on the microbiota and whether the effects are short-term or persist long-term remain uncertain. In this review, we summarise studies that have investigated the effect of antibiotics on the composition of the human intestinal microbiota.Methods: A systematic search was done to identify original studies that have investigated the effect of systemic antibiotics on the intestinal microbiota in humans.Results: We identified 129 studies investigating 2076 participants and 301 controls. Many studies reported a decrease in bacterial diversity with antibiotic treatment. Penicillin only had minor effects on the intestinal microbiota. Amoxicillin, amoxcillin/clavulanate, cephalosporins, lipopolyglycopeptides, macrolides, ketolides, clindamycin, tigecycline, quinolones and fosfomycin all increased abundance of Enterobacteriaea other than E. coli (mainly Citrobacter spp., Enterobacter spp. and Klebsiella spp.). Amoxcillin, cephalosporins, macrolides, clindamycin, quinolones and sulphonamides decreased abundance of E. coli, while amoxcillin/clavulante, in contrast to other penicillins, increased abundance of E. coli. Amoxicllin, piperacillin and ticarcillin, cephalosporins (except fifth generation cephalosporins), carbapenems and lipoglycopeptides were associated with increased abundance of Enterococcus spp., while macrolides and doxycycline decreased its abundance. Piperacillin and ticarcillin, carbapenems, macrolides, clindamycin and quinolones strongly decreased the abundance of anaerobic bacteria. In the studies that investigated persistence, the longest duration of changes was reported after treatment with ciprofloxacin (one year), clindamycin (two years) and clarithromycin plus metronidazole (four years). Many antibiotics were associated with a decrease in butyrate or butryrate-producing bacteria.Conclusion: Antibiotics have profound and sometimes persisting effects on the intestinal microbiota, characterised by diminished abundance of beneficial commensals and increased abundance of potentially detrimental microorganisms. Understanding these effects will help tailor antibiotic treatment and the use of probiotics to minimise this 'collateral damage'. [ABSTRACT FROM AUTHOR]

Root canal treatment addresses infectious processes that require control. Occasionally, the radicular pulp is vital and inflamed, presenting a superficial infection. To preserve pulpal remnants, conservative procedures have gained favor, employing anti-inflammatory medications. This study investigated the effects of propolis (PRO), and copaiba oil-resin (COR) associated with hydrocortisone (H) and compared their impact to that of Otosporin® concerning cytotoxic and genotoxic activity, cytokine detection, and toxicity in the Galleria mellonella model. Human periodontal ligament fibroblasts (PDLFs) were exposed to drug concentrations and evaluated by the MTT assay. Associations were tested from concentrations that did not compromise cell density. Genotoxicity was evaluated through micronucleus counting, while cytokines IL-6 and TGF-β1 were detected in the cell supernatant using ELISA. Molecular docking simulations were conducted, considering the major compounds identified in PRO, COR, and H. Increasing concentrations of PRO and COR were assessed for acute toxicity in Galleria mellonella model. Cellular assays were analyzed using one-way ANOVA followed by Tukey tests, while larval survivals were evaluated using the Log-rank (Mantel-Cox) test (α = 0.05). PRO and COR promoted PDLFs proliferation, even in conjunction with H. No changes in cell metabolism were observed concerning cytokine levels. The tested materials induce the release of AT 1 R, proliferating the PDFLs through interactions. PRO and COR had low toxicity in larvae, suggesting safety at tested levels. These findings endorse the potential of PRO and COR in endodontics and present promising applications across medical domains, such as preventive strategies in inflammation, shedding light on their potential development into commercially available drugs. [Display omitted] • Propolis and copaiba oil-resin can promote a proliferative action on human cells. • Cytokine levels do not change after the application of natural antimicrobial compounds. • Natural antimicrobial compounds and associations with hydrocortisone induce AngII. • AT 1 R liberation suggests effects on inflammatory reactions and cell proliferation. • Propolis and copaiba oil-resin are not toxic to Galleria mellonella. [ABSTRACT FROM AUTHOR]

[Display omitted] • Mono and binuclear stable metal chelates with bio-potent novel Schiff base ligands of N, O and S donors are engrossed. • Thiosemicarbazides and 1,3,4 thiadizole have been advanced for copious biological investigations. • Chelation, structure diversity and stability of metal complexes prompt in reinforcement the antimicrobial potency of metal complexes. • Assessment executed for biological potential of synthesized Schiff base ligands and complexes. Metal complexes of Schiff base ligands (exhibit imine -C = N- functional group) derived from thiosemicarbazide and 1,3,4 thiadiazole have attracted the attention of researchers on account of excellent broad range applications in a variety of fields from material sciences to biological sciences. Broad range of factors such that involvement of N, S, and O donor atoms, chelating property, chemical adaptability, minimum toxicity owing to -N-C = S linkage, structure topologies and diversity, polydentate ligands, aromaticity, extended conjugations in 1,3,4 thiadiazole and stability accommodate pharmacological potential. Widespread organic precursors (aromatic aldehyde and primary amine) have been used for the development of novel Schiff base ligands and metal complexes. Metal chelates inclusive of d-block transition metals and non-transition metals with broad distinct features have also been synthesized and evaluated via various classical and advanced spectral and analytical techniques. This review encompasses the synthesis, spectral studies and investigations that have been reported for Thiosemicarbazides, 1,3,4 thiadiazole Schiff base derivatives of transition metal complexes followed by evaluation of wide variety of biological applications. This review summarizes advancements in research over the last 15 years (2007–2022). [ABSTRACT FROM AUTHOR]

• Saponins from Sapindus mukorossi and Quillaja saponaria increased octanol–water coefficient of Polymyxin B. • Plant surfactants changed the Polymyxin B particle size distribution indicating the formation of agglomerates. • Tested plant surfactants increased the freezing point of Polymyxin B water solutions. Knowing and understanding the interactions between surfactants and pharmaceuticals is crucial for the proper and efficient design of drug delivery systems. The goal of such systems is to ensure that the drug is as bioavailable to cells as possible. The subject of this study was the effect of natural surfactants, saponins from Quillaja saponaria Mol. and Sapindus mukorossi L. , on the behavior of the antibiotic Polymyxin B in aqueous solutions at 30 °C and atmospheric pressure. The conducted research showed that the tested surfactants in the concentration range up to 5 mg mL−1 did not affect the solubility of the antibiotic, but increased the value of the octanol–water partition coefficient (K ow). At concentrations of plant saponins from both sources, K ow slightly increased from 0.19 (control sample) to 0.40 (at 5 mg mL−1). The presence of surfactants also led to changes in the particle size distribution of Polymyxin B solutions and also in their zeta potential values. There was also a clear effect of saponins on the freezing point of the Polymyxin solution, but no significant changes in the melting point were observed. The collected results provide new knowledge about the interactions of plant surfactants and peptides based on the example of Polymyxin B, which opens wider possibilities for their use in drug delivery systems. [ABSTRACT FROM AUTHOR]

Previous epidemiological and animal studies have showed the lipid metabolic disruption of antimicrobial triclocarban (TCC) and triclosan (TCS). However, the present in vivo researches were mainly devoted to the hepatic lipid metabolism, while the evidence about the impacts of TCC/TCS on the adipose tissue is very limited and the potential mechanism is unclear, especially the molecular initiation events. Moreover, little is known about the toxic difference between TCC and TCS. This study aimed to demonstrate the differential adipogenic activity of TCC/TCS as well as the potential molecular mechanism via peroxisome proliferator-activated receptors (PPARα/β/γ). The in vitro experiment based on 3T3-L1 cells showed that TCC/TCS promoted the differentiation of preadipocytes into mature adipocytes at nanomolar to micromolar concentrations, which was approach to their human exposure levels. We revealed for the first time by reporter gene assay that TCC could activate three PPARs signaling pathways in a concentration-dependent manner, while TCS only activate PPARβ. The molecular docking strategy was applied to simulate the interactions of TCC/TCS with PPARs, which explained well the different PPARs activities between TCC and TCS. TCC up-regulated the mRNA expression of three PPARs, but TCS only up-regulated PPARβ and PPARγ significantly. Meanwhile, TCC/TCS also promoted the expression of adipogenic genes targeted by PPARs to different extent. The cellular and simulating studies demonstrated that TCC exerted higher adipogenic effects and PPARs activities than TCS. Our mice in vivo experiment showed that TCC could lead to adipocyte size increase, adipocyte lipid accumulation growing, fat weight and body weight gain at human-related exposure levels, and high fat diet exacerbated these effects. Moreover, male mice tended to be more susceptible to TCC induced obesogenic effect than female mice. This work highlights the potential obesogenic risks of TCC/TCS via PPARs signaling pathways, and TCC deserves more concerns for its higher activity. [Display omitted] • TCC and TCS promoted 3T3-L1 adipogenic differentiation at human-related levels. • TCC activated three PPARs signaling pathways while TCS only activate PPARβ. • TCC exhibited higher adipogenic effects and PPARs activity than TCS. • TCC and TCS up-regulated PPARs and adipogenesis-related target genes. • TCC exerted obesogenic effects on female and male mice at human exposure levels. [ABSTRACT FROM AUTHOR]

The microorganism control in packaged tofu by radio frequency (RF) heating combined with antimicrobial agents was investigated. The inactivation of vegetative cells and spores by RF heating alone or in combination with antimicrobial agents was evaluated. Results showed that vegetative cells of typical food microorganisms, such as E. coli, S. aureus , and Bacillus subtilis , were completely inactivated by RF heating at 80 °C for 20 min, while no significant reduction in the population of spores was observed. Additionally, the growth of Bacillus spores was effectively inhibited by 0.312 mg/g of nisin. The total viable count (TVC) in RF-treated packaged tofu was below 2 log CFU/g during the storage at 4 or 37 °C for 10 days in the presence of nisin. Furthermore, the quality analysis indicated that the pH, texture, color, and volatile profile of samples were well maintained, which contributed to the favorable sensory acceptance of the consumers. These results suggested that effective microorganism control in packaged tofu was achieved by combining RF heating and nisin. The developed method was recommended to prevent spoilage of packaged tofu and extend its shelf-life. [Display omitted] • Typical food microorganisms in packaged tofu were inactivated by RF heating. • 0.312 mg/g of nisin could effectively inhibited the growth of Bacillus spores. • Effective microbial control was realized by combined RF heating and nisin. • Favorable quality properties and sensory acceptance were obtained during storage. [ABSTRACT FROM AUTHOR]

Waterborne disease transmission is just one of several environmental and human health risks posed by biological water pollution. The public health crisis posed by biological contamination has prompted intensive research into the development of antimicrobial agents for preventing bacterial growth, stopping biofilm formation, and disinfection. Traditional water treatment procedures frequently fail to properly eliminate microbiological pollutants, necessitating the use of alternate methods. By enabling the production of nanoparticles with superior antibacterial characteristics, the growing science of nanotechnology provides intriguing possibilities. Metal-organic frameworks (MOFs) have recently gained attention as potential materials for antimicrobial applications due to their highly functionalized structures and porous crystalline nature. MOFs are composed of inorganic metal ions and organic linkers. This review aims to explore into various MOFs possessing antimicrobial properties and explores their synthesis techniques and characterization approaches. The study investigates how the conjugation of nanoparticles to MOFs affects their structural features, such as porosity, structure, pore volume, and surface area, as well as their antimicrobial efficacy. The design principles of effective MOF-based antimicrobial materials, including their components, fundamental antibacterial mechanisms, and assessment of antimicrobial activities, are thoroughly examined. The research also investigates the antibacterial, antifungal, and antiviral capabilities of different types of MOFs, showcasing their potential for purifying water contaminated with various harmful microbes. Furthermore, this study intends to contribute to the progress of sustainable and efficient ways for water purification and microbial control by thoroughly investigating the synthesis methods, characteristics, and antibacterial efficacy of MOF-based nanomaterials. [Display omitted] • Metal-organic frameworks (MOFs) can serve as potent antimicrobial agents. • MOFs are composed of inorganic metal ions and organic linkers. • Highly functionalized and porous MOF structure makes it ideal antibacterial agent. • Conjugation of nanoparticles to MOFs improves their antimicrobial efficacy. • MOF can be a sustainable and effective material for water purification systems. [ABSTRACT FROM AUTHOR]

Quantitative measurement of cell lysis against a given microbial strain is essential to calculate the antimicrobial potency of protein/peptide/nanomaterial based formulations. Fluorescence spectroscopy based measurements offer precise quantification of a process via selected flurophore emission profile. In this context, we elucidate a reliable and robust green fluorescent protein (GFP) based fluorescence spectroscopy protocol to evaluate the antimicrobial activity of proteins. The technique is based on the fact that the intensity of the GFP emission released from cells correlates with cell lysis and henceforth the antimicrobial potential of the chosen agent. The technique was demonstrated with two different families of bacteriophage endolysins (T7 and T4 endolysins) using GFP expressing E. coli cells. The GFP based method allowed the absolute quantification of T4 and T7 endolysins cell lysis characteristics at different pH, salt concentrations, and metal ions. The results obtained from GFP based fluorimetric assay were substantiated with turbidimetric assay and fluorescence microscopy. This fluorimetric method in conjugation with different GFP expressing microbial strains and antimicrobial agents can be efficiently applied as a quantification technique to precisely measure cell lysis. Unlabelled Image • Devised a novel GFP based fluorescence assay to quantify bacterial cell lysis • Demonstrated the fluorimetric assay using bacteriophage T4 and T7 endolysins • The GFP based assay is robust over a range of pH, salt and metal conditions. • Endolysin's enzymatic activity correlated well with GFP fluorescence profiles. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate antibacterial properties of the colloidal silver nanoparticles (SNPs) and eugenol, alone and in combination, on Staphylococcus aureus and Salmonella Typhimurium and their interactions with food constituents (fat, protein, and carbohydrate). We examined antibacterial activities of SNPs and eugenol in Luria-Bertani (LB) broth and 1.5 and 3% fat ultrahigh-temperature (UHT) milk. MICs of eugenol and SNPs (particle size of 31.3 nm) were also investigated in the presence of sunflower oil, meat extract, and starch at concentrations of 2, 5, and 10% to examine the interactions between food constituents and antimicrobial agents. MICs and MBCs of eugenol and SNPs for both bacteria were at 2,500 and 25 μg/mL, respectively. Combinations of the two substances had additive and synergistic effects on Salmonella Typhimurium and S. aureus, respectively. Both compounds had bactericidal activity. In food matrices, results indicated that eugenol only in sunflower oil at 5 and 10% concentrations had significant antibacterial activity. A similar result was achieved for SNPs with 10% meat extract. In LB broth, eugenol at 2,500 and 5,000 μg/mL achieved 6-log reductions in the microbial population of both bacteria after 3 h, while SNPs achieved the same effect after 9 h. In UHT milk with 1.5% fat, eugenol at 5,000 μg/mL and SNPs at 25 μg/mL achieved 6-log reductions in bacterial populations after 24 h. Thus, the antimicrobial activity of both eugenol and SNPs depended on the medium in which the experiment was conducted, and the combination of both antimicrobial agents increased the antimicrobial effect. The interactions of eugenol, nanoparticles, and food constituents were investigated. Eugenol and SNP had synergistic effects on S. aureus. Protein and lipids reduced the efficacy of eugenol. Protein negatively impacted the activity of SNPs. [ABSTRACT FROM AUTHOR]

Aromatic essential oils (EO) are important plant extracts that have attracted great interest for their various biological activities and their potential to replace chemical preservatives in the field of food preservation. Moreover, the volatility of EOs has further expanded their applications in antibacterial packaging (AP) systems. This review focuses on the contributions of EOs to food packaging by (1) introducing the antibacterial activity of EOs; (2) summarizing the implementation of EO-APs; (3) analyzing the applications of EO-APs in food preservation; and (4) assessing the safety of EOs. Understanding the different combinations of EOs and food packaging will help improve the effectiveness of EO-APs in food preservation and better target their use, which will promote their application in food systems. By combining them with packaging materials, the adverse flavor of EOs can be reduced and their action time prolonged, which will greatly improve their effective utilization rate in food preservation. • Essential oils can be used as ingredients of active food packaging. • Introduced the main active ingredients and antibacterial effects of EOs commonly used in food preservation. • Focused on summarizing the implementation of EOs-AP. • Analyzed the application of EOs-AP in food preservation. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Thermally activated persulfate induced TCS and TCC degradation in soils. • TCS degradation rate was dramatically affected by soil properties. • SOM and soil particle size distribution varied during TCS degradation. • Transformation pathway was proposed for TCS degradation in soil. Abstract As a widely used antimicrobial agent, Triclosan (TCS) may potentially enter the environment, thus invoking significant environmental concerns due to its high toxicity to organisms. The present study demonstrated that a thermally activated persulfate (PS) oxidation process could effectively degrade the TCS in various arable topsoils. Eighty percent of the TCS at 50 mg kg−1 in Zhe Jiang (ZJ) soil could be degraded after a 360 min reaction in the presence of 18.8 mM of PS. Increased PS concentrations significantly increased the efficiency of the degradation. Elevated temperatures were favorable for TCS degradation, and the apparent activation energy E a was determined to be 74.3 kJ mol−1. The oxidation efficiency gradually decreased with the increase of the pH from 3 to 11. An electron paramagnetic resonance (EPR) experiment and radical scavenging test confirmed that both OH and SO 4 − existed during oxidation, and SO 4 − was the dominant radical species. The degradation efficiency of TCS was higher than that of Triclocarban (TCC), another widely used antimicrobial agent, which might be attributed to the electro-donating phenolic (–OH) and ether (–O–) groups in the molecular structure of TCS. The degradation of TCS in three arable topsoils indicated that the soil organic matter played a dominant role in TCS degradation. In ZJ soil, after the oxidation process, the soil's SOM was decreased by 14%, and the breakdown of large soil aggregates into smaller ones was found. Moreover, two degradation products of TCS were identified, e.g., penta-hydroxylated and hexa-hydroxylated TCS, which may be less toxic. The degradation was induced by phenol ring hydroxylation, and the underlying oxidation mechanisms are given. [ABSTRACT FROM AUTHOR]

We investigated the impact of chitosan and oregano essential oil (EO) individually or in combination on the quality of eel fillets in vacuum packaging (VP) and stored under refrigeration (4°C). Treatments studied were (i) control eel fillets stored in VP (E), (ii) eel fillets treated with 0.3% (v/w) oregano EO and stored in VP (E-OR), (iii) eel fillets treated with 2.0% (w/v) chitosan and stored in VP (E-CH), and (iv) eel fillets treated with 2.0% (w/v) chitosan and 0.3% (v/w) oregano EO and stored in VP (E-CH- OR). Treatments E-CH-OR and E-CH significantly reduced counts of mesophilic bacteria, Pseudomonas, Shewanella, and yeasts and molds during storage. Use of chitosan alone or in combination with oregano EO led to a significant reduction in concentrations of trimethylamine nitrogen and total volatile basic nitrogen in fillets, which led to lower concentrations of thiobarbituric acid reactive substances compared with the control samples. The eel samples in the E-CH and E-CH-OR groups were sensorially acceptable during the entire refrigerated storage period of 18 days. Presence of chitosan in the E-CH and E-CH-OR fillets did not negatively affect the taste of the fillets. E-CH fillets received a higher taste score than did E-CH-OR fillets probably because of the distinct and ‘‘spicy’’ lemon taste of chitosan, which was well received by the sensory panel. Based on overall sensory data (based on mean sensory scores of odor and taste), the shelf life was 6 days for the control fillets, 10 days for the E-OR fillets, and >18 days for the E-CH and E-CH-OR fillets stored in VP at 4°C. Overall, chitosan-treated eel fillets had lower microbial loads and a longer shelf life compared with the controls. Chitosan-treated eel fillets were preferred over oregano-treated fillets. Chitosan alone or in combination with oregano could be used as a preservative treatment and shelf-life extender for other seafoods. [ABSTRACT FROM AUTHOR]

Antimicrobial agents are used widely in veterinary and human medicine worldwide. However, their use has suffered a major setback globally due to the emergence of antimicrobial resistance (AMR) in a wide range of microorganisms. This study aimed to investigate the prevalence of AMR in household milk for human consumption in Isiolo County, Kenya. The study identified 42 Escherichia coli (E.coli) isolates from 304 milk samples that were collected in randomly selected households in northern Kenya. E. coli was isolated using Eosin Methylene Blue Agar and identified using biochemical tests. The isolates were confirmed using Polymerase Chain Reaction (PCR) and sequencing. The antimicrobial resistance profiles of the isolates to 11 antimicrobial agents were evaluated by disc diffusion method on Mueller Hinton Agar. Additionally, the isolates were evaluated for antimicrobial genetic determinants conferring the resistance phenotypes to beta-lactams and tetracycline. Overall, 95% of the isolates were resistant to at least one of the tested antimicrobials. Large proportions (81%) of the isolates were resistant to beta-lactams followed by tetracycline (55%) and streptomycin (29%). All the isolates were, however, susceptible to ciprofloxacin and nalidixic acid. Multidrug resistance (MDR) was observed in 14.28% of the isolates and beta-lactam resistant isolates were confirmed to be harbouring bla SHV , bla TEM and bla CTX-M genes. The demonstration of AMR determinants and especially Extended Spectrum Beta Lactamase (ESBL) carriers in milk reveals the risk posed to food safety, particularly to communities that consume raw milk. This study found that raw milk consumed in Isiolo County was contaminated with resistant strains of E. coli. There is, therefore, a need to determine the sources of this resistance and implement interventions to reduce the emergence and spread of AMR bacteria. We recommend implementation of measures that could reduce the presence of antimicrobial resistant E. coli strains in raw milk food chain. • E. coli was detected in 13.8% of the milk samples. • Ninety five (95%) of E. coli were resistant to at least one of the tested antimicrobials. • E. coli was highly resistant to beta-lactams (81%) and tetracycline (55%). • Multidrug resistance (MDR) was observed in 14.28% of the E. coli isolates. [ABSTRACT FROM AUTHOR]

The emergence of multidrug resistant (MDR) pathogens is a global threat and has created problems in providing adequate treatment of many infectious diseases. Although the conventional antimicrobial agents are quite effective against several pathogens, yet there is a need for more effective antimicrobial agents against MDR pathogens. Herbal drugs and phytochemicals have been used for their effective antimicrobial activity from ancient times and there is an increasing trend for development of plant based natural products for the prevention and treatment of pathogenic diseases. One of the strategies for effective resistance modification is the use of antimicrobial agent-phytochemical combinations that will neutralize the resistance mechanism, enabling the drug to still be effective against resistant microbes. These phytochemicals can work by several strategies, such as inhibition of target modifying and drug degrading enzymes or as efflux pumps inhibitors. A plethora of herbal extracts, essential oils and isolated pure compounds have been reported to act synergistically with existing antibiotics, antifungals and chemotherapeutics and augment the activity of these drugs. Considerable increases in the susceptibility pattern of several microbes towards the natural antimicrobials and their combinations were observed as indicated by significant decline in minimum inhibitory concentrations. This review paper summarizes the current developments regarding synergistic interactions of plant extracts and isolated pure compounds in combination with existing antibacterial, antifungal agents and chemotherapeutics. The effect of these agents on the susceptibility patterns of these pathogens and possible mechanisms of action are described in detail. In conclusion, many phytochemicals in combination with existing drugs were found to act as resistance modifying agents and proper combinations may rescue the efficacy of important lifesaving antimicrobial agents. Image 1 • Emergence of MDR pathogens is a global issue. • Phytochemicals in combination with classical drugs can synergistically act to reverse resistance mechanisms. • They can inhibit antibiotic degrading enzyme, prevent target modification, block efflux pumps. • They can synergize with antifungal and antiviral agents. • Clinical trials and advance studies are required for their future clinical uses. [ABSTRACT FROM AUTHOR]

TMCA (3,4,5-trimethoxycinnamic acid) ester and amide are privileged structural scaffolds in drug discovery which are widely distributed in natural products and consequently produced diverse therapeutically relevant pharmacological functions. Owing to the potential of TMCA ester and amide analogues as therapeutic agents, researches on chemical syntheses and modifications have been carried out to drug-like candidates with broad range of medicinal properties such as antitumor, antiviral, CNS (central nervous system) agents, antimicrobial, anti-inflammatory and hematologic agents for a long time. At the same time, SAR (structure-activity relationship) studies have draw greater attention among medicinal chemists, and many of the lead compounds were derived for various disease targets. However, there is an urgent need for the medicinal chemists to further exploit the precursor in developing chemical entities with promising bioactivity and druggability. This review concisely summarizes the synthesis and biological activity for TMCA ester and amide analogues. It also comprehensively reveals the relationship of significant biological activities along with SAR studies. Image 1 • 3,4,5-Trimethoxycinnamic acid (TMCA) derivatives show applications in different pathophysiological conditions due to its privileged structural scaffolds. • Natural derived TMCA analogues and chemically modified TMCA ester and amide analogues and their bioactivities are focused in this review. Additionally, it also comprehensively summarized the relationship of significant biological activities along with SAR studies of synthetic TMCA derivatives. [ABSTRACT FROM AUTHOR]

The alarming burden of antibiotic resistance in nosocomial pathogens warrants the discovery and development of new and effective antimicrobial compounds. Small cationic antimicrobial peptides seem to be a promising therapeutic alternative to fight multi-drug resistance. This study investigated the in-vitro potential of a previously reported lantibiotic, paenibacillin, from the clinical perspective. An antimicrobial peptide, M152-P4, was isolated, purified and characterized from a mud isolate, and its susceptibility was determined in clinical isolates of Staphylococcus aureus and Enterococcus spp. Time-kill kinetics, resistance, probable mode of action, haemolytic activity and mammalian cytotoxicity were investigated. M152-P4 was identified as paenibacillin based on mass spectroscopy data, amino acid analysis and biosynthetic gene cluster analysis. It had potent antibacterial activity against the Gram-positive pathogens tested, with minimum inhibitory concentrations from 0.1 to 1.56 µM. It appeared very challenging for S. aureus to develop resistance to this compound. Also, paenibacillin penetrated the outer layer of bacteria, and depolarized the membrane completely by creating pores in the plasma membrane with better potential than nisin. Paenibacillin showed no haemolysis up to 60 µM, and the half maximal inhibitory concentration on mammalian cell lines was >100 µM. These results highlight the excellent antibacterial properties of paenibacillin in clinically relevant pathogens. It is stable in the presence of serum, and non-haemolytic and non-cytotoxic even above the therapeutic concentration. Further research efforts regarding toxicity and in-vivo efficacy are necessary to develop paenibacillin as a next-generation therapeutic drug to overcome multi-drug resistance in Gram-positive pathogens. [ABSTRACT FROM AUTHOR]