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Context: The emergence of pan-resistant bacteria requires the development of new antibiotics and antibiotic potentiators. Objective: This review identifies antibacterial phenolic compounds that have been identified in Asian and Pacific Angiosperms from 1945 to 2023 and analyzes their strengths and spectra of activity, distributions, molecular masses, solubilities, modes of action, structures-activities, as well as their synergistic effects with antibiotics, toxicities, and clinical potential. Methods: All data in this review was compiled from Google Scholar, PubMed, Science Direct, Web of Science, and library search; other sources were excluded. We used the following combination of keywords: 'Phenolic compound', 'Plants', and 'Antibacterial'. This produced 736 results. Each result was examined and articles that did not contain information relevant to the topic or coming from non-peer-reviewed journals were excluded. Each of the remaining 467 selected articles was read critically for the information that it contained. Results: Out of ∼350 antibacterial phenolic compounds identified, 44 were very strongly active, mainly targeting the cytoplasmic membrane of Gram-positive bacteria, and with a molecular mass between 200 and 400 g/mol. 2-Methoxy-7-methyljuglone, [6]-gingerol, anacardic acid, baicalin, vitexin, and malabaricone A and B have the potential to be developed as antibacterial leads. Conclusions: Angiosperms from Asia and the Pacific provide a rich source of natural products with the potential to be developed as leads for treating bacterial infections. [ABSTRACT FROM AUTHOR]

Context The emergence of pan-resistant bacteria requires the development of new antibiotics and antibiotic potentiators.Objective This review identifies antibacterial phenolic compounds that have been identified in Asian and Pacific Angiosperms from 1945 to 2023 and analyzes their strengths and spectra of activity, distributions, molecular masses, solubilities, modes of action, structures-activities, as well as their synergistic effects with antibiotics, toxicities, and clinical potential.Methods All data in this review was compiled from Google Scholar, PubMed, Science Direct, Web of Science, and library search; other sources were excluded. We used the following combination of keywords: ‘Phenolic compound’, ‘Plants’, and ‘Antibacterial’. This produced 736 results. Each result was examined and articles that did not contain information relevant to the topic or coming from non-peer-reviewed journals were excluded. Each of the remaining 467 selected articles was read critically for the information that it contained.Results Out of ∼350 antibacterial phenolic compounds identified, 44 were very strongly active, mainly targeting the cytoplasmic membrane of Gram-positive bacteria, and with a molecular mass between 200 and 400 g/mol. 2-Methoxy-7-methyljuglone, [6]-gingerol, anacardic acid, baicalin, vitexin, and malabaricone A and B have the potential to be developed as antibacterial leads.Conclusions Angiosperms from Asia and the Pacific provide a rich source of natural products with the potential to be developed as leads for treating bacterial infections.

Sandip Patil, Xinye Li, Huirong Mai, Ying Wang, Xue Tang, Sixi Liu, Feiqiu Wen Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of ChinaCorrespondence: Sixi Liu; Feiqiu Wen, Email tigar467@126.com; fwen62@163.comBackground: This case report underscores the intricate challenges in managing paediatric patients with acute myeloid leukaemia (AML) undergoing intensive chemotherapy, particularly when complicated by the emergence of multidrug-resistant pathogens such as Carbapenem-Resistant Pseudomonas aeruginosa (CRPA).Case Presentation: An 11-year-old male with AML presented with skin purpura and persistent cough. Clinical and laboratory assessments revealed a high-risk AML profile with genetic mutations, leading to the initiation of intensive chemotherapy per the C-HUANA-AML-2015 protocol. Despite successful disease remission after initial chemotherapy courses, the patient experienced unexpected complications. Notably, septic shock, bone marrow failure, and the emergence of CRPA were encountered during the clinical course. Septic shock occurred following Course B3 chemotherapy, marked by a fever unresponsive to initial antibiotic therapy. Despite negative blood cultures, meropenem and vancomycin were initiated, successfully normalizing temperature. Subsequent challenges included persistent bone marrow suppression, perianal dermatitis, and the identification of CRPA in stool cultures, leading to altered antibiotic therapy guided by minimum inhibitory concentration (MIC) considerations. Whole-genome sequencing (WGS) of the CRPA strain revealed a highly virulent clone (ST-970) with numerous resistance and virulence genes.Conclusion: This case report offers new insights into the complexities of pediatric AML management, with a focus on the emergence of CRPA. The discovery of a high-risk CRPA clone with detailed genomic data underscores the growing challenge of antimicrobial resistance in pediatric oncology. The persistent presence of CRPA and ongoing bone marrow failure highlight the difficulties in managing these complications. This case calls for a reassessment of treatment strategies and encourages further research to improve outcomes in pediatric AML, emphasizing the need for a multidisciplinary approach to address infectious complications and antimicrobial resistance.Keywords: acute myeloid leukaemia, carbapenem-resistant Pseudomonas aeruginosa, paediatric oncology, antimicrobial resistance, superbugs

Mainly performed within a rapid diagnostic tests company, a lateral flow (LF) system using gold nanoparticles (AuNPs) as transducers is presented able to detect three bacteria of interest, of relevance for antimicrobial resistance (AMR): Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), and Klebsiella pneumoniae, with a limit of detection of 25 ng/mL of glutamate dehydrogenase (GDH) for C. difficile, 36 ng/mL of penicillin-binding protein 2a (PBP2a) for MRSA, and 4 × 106 CFU/mL for K. pneumoniae. The system showed good results with bacteria culture samples, is user-friendly, and suitable for rapid testing, as the results are obtained within 15 min. [ABSTRACT FROM AUTHOR]

Bacterial evolution, particularly in hospital settings, is leading to an increase in multidrug resistance. Understanding the basis for this resistance is critical as it can drive discovery of new antibiotics while allowing the clinical use of known antibiotics to be optimized. Here, we report a photoactive chemical probe for superresolution microscopy that allows for the in situ probing of antibiotic-induced structural disruption of bacteria. Conjugation between a spiropyran (SP) and galactose via click chemistry produces an amphiphilic photochromic glycoprobe, which self-assembles into glycomicelles in water. The hydrophobic inner core of the glycomicelles allows encapsulation of antibiotics. Photoirradiation then serves to convert the SP to the corresponding merocyanine (MR) form. This results in micellar disassembly allowing for release of the antibiotic in an on-demand fashion. The glycomicelles of this study adhere selectively to the surface of a Gram-negative bacterium through multivalent sugar-lectin interaction. Antibiotic release from the glycomicelles then induces membrane collapse. This dynamic process can be imaged in situ by superresolution spectroscopy owing to the "fluorescence blinking" of the SP/MR photochromic pair. This research provides a high-precision imaging tool that may be used to visualize how antibiotics disrupt the structural integrity of bacteria in real time. [ABSTRACT FROM AUTHOR]

Background: The increased prevalence of antibiotic-resistant bacterial pathogens has substantially decreased the efficacy of some antibiotics and has rendered others completely ineffective. Widespread bacterial resistance to ß-lactam antibiotics (including resistance to the second-generation drug methicillin) is particularly concerning and new antibiotic therapies are urgently needed. Materials and Methods: The antibacterial activity of commercially sourced water-soluble Eucalyptus major and Melaleuca alternifolia leaf solutions was screened against ß-lactam resistant and sensitive bacterial strains of Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus using disc diffusion assays. The activity was quantified by broth microdilution minimum inhibitory concentration (MIC) assays. Toxicity was evaluated by testing Artemia nauplii mortality assays. Results: Methanolic and aqueous extracts prepared from Eucalyptus major and Melaleuca alternifolia leaves displayed noteworthy growth inhibitory activity against all of the bacteria tested, including against methicillin resistant Staphylococcus aureus MRSA and extended spectrum ß-lactamase (ESBL) strains of E. coli and K. pneumoniae. The methanolic E. major leaf extract had particularly good antibacterial activity (MICs=39-625 µg/mL) against all bacterial strains. Notably, this extract had similar potency against an ESBL strain of E. coli as against the corresponding antibiotic-sensitive strain (MICs=78 µg/mL against each) and was significantly more potent against an ESBL K. pneumoniae strain (MIC=39 µg/mL) than against the corresponding antibiotic sensitive strain (MIC=78 µg/mL). All extracts were non-toxic in the Artemia nauplii lethality assay (ALA), indicating their safety for topical use. Conclusion: The potency of the E. major and M. alternifolia extracts against multi-antibiotic resistant bacteria and their lack of toxicity highlight these species as potential targets for antibiotic drug development. Further phytochemical and mechanistic studies of these species are warranted. [ABSTRACT FROM AUTHOR]

Antibiotic resistance (AR) is a growing health crisis that has remained underrepresented in coverage across major news publications in the U.S. despite increasing rates of related disease outbreaks and mortality worldwide. This study used content analysis to examine the coverage of AR in two major U.S. news publications before the COVID-19 pandemic (2018-2019) and during it (2020-2021). Coverage of AR in The New York Times (NYT) and The Washington Post (WP) was analyzed according to the use of frames, the quantity of articles published, and a number of other variables including stakeholders, diseases, and terms referring to AR. These factors were used to assess how coverage of AR differed before and during the COVID-19 pandemic, and how it differed between the two newspapers. Pre-COVID-19 coverage focused on AR as an isolated pandemic, while coverage during the early years of the COVID-19 pandemic often used AR as a supplementary component of the coverage to the main topic of COVID-19. This study found that both before and during the outbreak of COVID-19, the majority of the observed articles did not fully explain the scope, severity, or solution for the AR crisis. Instead, they provided readers with baseline information, framing AR as a contemporary issue and generally encouraging action but included very few tangible suggestions for every day, individual action for readers. [ABSTRACT FROM AUTHOR]

Background: Detection of K. pneumoniae superbugs carrying Extended-spectrum β-lactamase (ESBL) and Carbapenemase resistance genes among hospitalized patients is crucial for infection control and prevention. The aim of this molecular study was to investigate the spread of ESBL and Carbapenemase-producing K. pneumoniae in two hospitals located in Southwest Iran. Methods: One hundred clinical isolates of K. pneumoniae were randomly collected from two hospitals over a period of five months, from November 2023. The isolates were confirmed using biochemical and genotypic tests. According to the CLSI 2022 guidelines, K. pneumoniae isolates that exhibited resistance to at least one of the three indicator cephalosporins or carbapenems were selected for evaluation of ESBL and carbapenemase production. This was done using a combination disk confirmatory test and the modified carbapenem inactivation method (mCIM). Finally, the presence of ESBLs and carbapenemase resistance encoding genes was assessed using PCR and specific primers. Results: Out of the 100 isolates, the percentage of antibiotic resistance was cefoxitin (29 %), cefixime (28 %), ceftazidime (26 %), cefotaxime (24 %), cefepime (22 %), ceftriaxone (21 %), imipenem (20 %), and meropenem (17 %). Additionally, thirty isolated strains were found to be multidrug-resistant. Out of these, twenty-seven strains demonstrated a potential for ESBLs, twenty strains for Carbapenemase, and seventeen strains for both ESBLs and Carbapenemase production. Moreover, the occurrence of ESBLs and carbapenemase genes was as follows: blaSHV (25 %), blaTEM (23 %), blaCTX-M (20 %), blaOXA-48 (17 %), and blaVIM (13 %). It is important to mention that we did not detect the blaIMP and blaKPC. resistant genes among clinical isolates. Conclusion: Based on the results, the existence of this type of resistance in hospital centers needs to be reevaluated in terms of empirical antibiotic prescribing. Additionally, it is recommended that infection control measures should be taken for public health. Also, it's suggested that hospital-acquired infections caused by superbug K. pneumoniae resistant strains should be addressed.

“An impregnable stronghold where one or more warrior clans can evade enemy attacks'' may serve as a description of bacterial biofilm on a smaller level than human conflicts. Consider this hypothetical conflict: who would emerge victorious? The occupants of secure trenches or those carrying out relentless assault? Either faction has the potential for triumph; the defenders will prevail if they can fortify the trench with unwavering resolve, while the assailants will succeed if they can devise innovative means to breach the trench. Hence, bacterial biofilms pose a significant challenge and are formidable adversaries for medical professionals, often leading to the failure of antibiotic treatments in numerous hospital infections. Phage engineering has become the foundation for the targeted enhancement of various phage properties, facilitating the eradication of biofilms. Researchers across the globe have studied the impact of engineered phages and phage-derived enzymes on biofilms formed by difficult-to-treat bacteria. These novel biological agents have shown promising results in addressing biofilm-related challenges. The compilation of research findings highlights the impressive capabilities of engineered phages in combating antibiotic-resistant bacteria, superbugs, and challenging infections. Specifically, these engineered phages exhibit enhanced biofilm destruction, penetration, and prevention capabilities compared to their natural counterparts. Additionally, the engineered enzymes derived from phages demonstrate improved effectiveness in addressing bacterial biofilms. As a result, these novel solutions, which demonstrate high penetration, destruction, and inhibition of biofilms, can be regarded as a viable option for addressing infectious biofilms in the near future.

Antimicrobials or antibiotics were the important revelations of the last century, however, it came along with a silent curse that people care less to talk about. Antimicrobial resistance (AMR) which emerged alongside antibiotics in the last century has been a significant concern for scientists and policymakers. Since their discovery, it has been noted that the widespread use of antibiotics is the primary cause of bacteria developing antimicrobial drug resistance. Despite the recognition of this issue, it is challenging to curtail the widespread use of antibiotics because they are essential for treating various infections. Paradoxically, the necessity of using these drugs becomes an inadvertent advantage for bacteria to evolve resistance mechanisms. This dilemma creates a seeming stalemate in our battle against these tiny microorganisms. Delaying action could have dire consequences, potentially leading to the emergence of stronger superbugs that pose a serious threat to the entire human population. The recent COVID-19 pandemic serves as a stark reminder of the devastating impact a small microbe can have on global health. This paper delves into the mechanisms of antimicrobial resistance in bacteria, the evolution of superbugs and the innovative techniques employed by scientists to combat these challenges. Taking proactive steps is crucial to avoid a future where we are at the mercy of increasingly resilient microbes.

Introduction: Rapid increase in antimicrobial-resistance is leading to urgent need for newer broad-spectrum antimicrobials. Therefore, we have evaluated the antimicrobial résistance spectrum of India-discovered novel antibiotics (levonadifloxacin) against clinical isolates recovered from cancer patients. Materials and Methods: The study was conducted in the microbiology department, over a period of 1 year between May 2021 and June 2022 and 374 consecutive and nonduplicate Gram-positive (GPC) and MDR Gram Negative Bacteria (GNB) isolate were analyzed from 3,880 cancer patients in study. The identification and antimicrobial sensitivities of bacterial isolates were performed according to standard laboratory protocols by using automated identification system (VITEK-2-8.01; BioMérieux, Germany). The activity of levonadifloxacin and comparator antibiotics was evaluated using disk diffusion methods as per Clinical and Laboratory Standards Institute 2022 guidelines. Results: The mean age of the patients were 51.6 ± 14.59 years with male: female ratio of 1.2:1. The prevalence of GPC was 167 (44.65%) and MDR-GNB was 207 (55.34%). The most common GPC was Staphylococcus aureus; 97 (58.08%) followed by Enterococcus species 66 (39.52%). In GNB, Escherichia coli; 93 (44.92%) was the most common followed by Klebsiella pneumoniae; 45 (21.73%). Levonadifloxacin susceptibility was present in 98.7% methicillin-resistant S. aureus and 96% methicillin-susceptible S. aureus and 77.1% Enterococcus-species. Additionally, all the fluoroquinolones-resistant S. aureus isolates were susceptible to levonadifloxacin (WCK-771) except one isolate. Also, levonadifloxacin-(WCK-771) exhibits 100% susceptibility fluoroquinolone susceptible GNB, such as E. coli, K. pneumoniae, Pseudomonas species, and Acinetobacter species. Interestingly, all fluoroquinolones-resistant Salmonella species and Stenotrophomonas maltophilla exhibited 100% susceptibility to levonadifloxacin (WCK-771). Conclusion: Levonadifloxacin (WCK-771) possesses potent activity against all the MDR Gram-positive pathogens including the coverage of susceptible Enterobacterales and MDR S. maltophilla and Burkholderia cepacia suggesting its potential utility in the management of polymicrobial infections. [ABSTRACT FROM AUTHOR]

Antimicrobials or antibiotics were the important revelations of the last century, however, it came along with a silent curse that people care less to talk about. Antimicrobial resistance (AMR) which emerged alongside antibiotics in the last century has been a significant concern for scientists and policymakers. Since their discovery, it has been noted that the widespread use of antibiotics is the primary cause of bacteria developing antimicrobial drug resistance. Despite the recognition of this issue, it is challenging to curtail the widespread use of antibiotics because they are essential for treating various infections. Paradoxically, the necessity of using these drugs becomes an inadvertent advantage for bacteria to evolve resistance mechanisms. This dilemma creates a seeming stalemate in our battle against these tiny microorganisms. Delaying action could have dire consequences, potentially leading to the emergence of stronger superbugs that pose a serious threat to the entire human population. The recent COVID-19 pandemic serves as a stark reminder of the devastating impact a small microbe can have on global health. This paper delves into the mechanisms of antimicrobial resistance in bacteria, the evolution of superbugs and the innovative techniques employed by scientists to combat these challenges. Taking proactive steps is crucial to avoid a future where we are at the mercy of increasingly resilient microbes. [ABSTRACT FROM AUTHOR]

Background: Superbug resistance is a very rare, invincible global problem arising as a threat in hospitals as well as in the community. Methicillin-Resistant Staphylococcus aureus(MRSA), Vancomycin-Resistant Enterococci (VRE) and Multidrug-resistant Gram-negative bacilli (MDR-GNB) etc are the most deadly contagious strains. This study discloses the prevalence and risk factors associated with superbugs there by aiding the adoption of preventive measures to reduce resistance patterns in hospital settings. Aim: Identification of the superbug that predominantly shows antibiotic resistance in hospitals and analyzing the risk factors for the occurrence of antibiotic resistance. Materials and methods: A prospective observational study was conducted for one year, from 1st September 2019 to 31st July 2020 to evaluate the prevalence and risk factors of antibiotic-resistant superbugs among the 80 patients selected from the various departments (General Medicine, General Surgery, Nephrology, Pulmonology,Orthopedics, orthopaedicsurgery,Neurology, Urology,and Neurosurgery) of a tertiary care referral hospital. Results: Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were antibiotic-resistant superbugs that predominantly showed resistance in hospital settings. Conclusion: Pseudomonas aeruginosa and Methicillin-resistant superbugs were the predominantly found superbugs in hospital settings. Major risk factors for antibiotic-resistant superbugs were found to be Prolonged hospitalization, previous antibiotic therapy, failure to take the antibiotic as prescribed by physicians, patient co-morbid conditions, prophylactic use of antibiotics, patient diet etc.

Background & Aims: Non-Fermenting Gram-Negative Bacilli [NFGNB] which are considered as environmental contaminants have emerged as multidrug-resistant bacteria and are of serious concern to the treating physician. The aim of this study was to determine the proportion of metallo-beta-lactamase producing Pseudomonas aeruginosa and Acinetobacter species in clinical samples received in the Microbiology Laboratory and to study the antibiotic sensitivity pattern of metallo-beta-lactamase (MBL) producing strains. Materials & Methods: Various samples (pus, sputum, urine, blood and body fluids, etc.) were processed according to standard protocols. P.aeruginosa and Acinetobacter spp were isolated and identified with the help of various culture media, staining methods and biochemical reactions. Antibiotic susceptibility test was done by using Kirby-bauer disc diffusion method. MBL producers were identified using CLSI guidelines. Results: Out of 600 positive culture isolates from various samples, 65 (10.8%) were non-fermenting gram-negative bacilli, 40 (61.53%) were Pseudomonas aeruginosa, and 25 (38.47%) were Acinetobacter species. The overall incidence of MBL positive isolates in our study was 12.3% (8 of 65). All the isolates of Pseudomonas aeruginosa and Acinetobacterspecies were 100% sensitive to Colistin and Tigecycline. Conclusion: The study helps in understanding the antibiotic resistance pattern of isolates causing nosocomial infections, helping clinicians in making appropriate antibiotic choices as an empirical therapy and the policy-makers to bring out the measures in controlling the superbugs.

Antimicrobial resistance (AMR) is a growing global threat, especially in low- and middle-income countries (LMICs), causing prolonged illnesses, heightened antimicrobial use, increased healthcare expenses, and avoidable deaths. If not tackled, AMR could force 24 million people into severe poverty by 2030 and hinder progress on Sustainable Development Goals (SDGs). AMR spreads through interconnected ecosystems, with humans, animals, and the environment serving as reservoirs. Pharmaceutical wastewater, loaded with antibiotics and resistance genes, poses a significant environmental risk, mainly due to inadequate treatment and irresponsible disposal. The pharmaceutical industry is a notable contributor to environmental antibiotic pollution, with varying effluent management practices. Contaminated pharmaceutical wastewater discharge harms water sources and ecosystems. Urgent collaborative efforts are needed across policymakers, regulators, manufacturers, researchers, civil society, and communities, adopting a One Health approach to curb AMR's spread. Developing global standards for pharmaceutical effluent antibiotic residues, effective treatment methods, and improved diagnostics are vital in addressing AMR's environmental impact while safeguarding public health and the environment. National action plans should encompass comprehensive strategies to combat AMR. Preserving antibiotic efficacy and ensuring sustainable production require a united front from all stakeholders.

Abstract Background Antimicrobial resistance has already emerged as a major concern not only for public health but also for global economy. It causes a multifaceted crisis in development and growth by increasing the number of infections and deaths. Sustainable Development Goals are in place to ensure that development and growth are continual, as well as to end poverty, protect the environment, and promote peace and prosperity. In this review we tried to highlight the reasons for the prevalence of superbugs as well as their multifaceted impact on healthcare, and demonstrate potential ways to combat them and incorporate them into international policymaking processes. Main body of the abstract The literature review included articles from MEDLINE, EMBASE, Scopus, and PubMed published till the end of the year 2022 using keyword searches. Two hundred and forty-three research articles, review papers and studies written in English language evaluating the impact of Antimicrobial resistance (AMR) on patient, society and economy published until end of the year 2022 were included. Short conclusion This review highlighted the significant impact of antimicrobial resistance (AMR) on the Sustainable Development Goals (SDGs) and was able to identify at least five SDGs that are linked to healthcare. The emergence of superbugs results in increased expenditure, which has serious consequences for the global economy, particularly in developing countries where infectious diseases are prevalent. The overuse and misuse of antibiotics, as well as poor infection control practices, are identified as primary drivers of superbug emergence. However, implementing strategies such as rational antibiotic use, effective infection control practices, and developing new antibiotics and alternative therapies can mitigate the adverse effects of AMR and contribute to achieving the SDGs. It is essential to integrate AMR strategies into national development plans and improve cross-sectoral collaboration among stakeholders to combat superbugs effectively.

Multidrug resistance in bacterial strains known as superbugs is estimated to cause fatal infections worldwide. Migration and urbanization have resulted in overcrowding and inadequate sanitation, contributing to a high risk of superbug infections within and between different communities. The CRISPR-Cas system, mainly type II, has been projected as a robust tool to precisely edit drug-resistant bacterial genomes to combat antibiotic-resistant bacterial strains effectively. To entirely opt for its potential, advanced development in the CRISPR-Cas system is needed to reduce toxicity and promote efficacy in gene-editing applications. This might involve base-editing techniques used to produce point mutations. These methods employ designed Cas9 variations, such as the adenine base editor (ABE) and the cytidine base editor (CBE), to directly edit single base pairs without causing DSBs. The CBE and ABE could change a target base pair into a different one (for example, G-C to A-T or C-G to A-T). In this review, we addressed the limitations of the CRISPR/Cas system and explored strategies for circumventing these limitations by applying diverse base-editing techniques. Furthermore, we also discussed recent research showcasing the ability of base editors to eliminate drug-resistant microbes. [ABSTRACT FROM AUTHOR]

Thioredoxin (Trx) is essential in a redox-control system, with many bacteria containing two Trxs: Trx1 and Trx2. Due to a Trx system's critical function, Trxs are targets for novel antibiotics. Here, a 1.20 Å high-resolution structure of Trx2 from Acinetobacter baumannii (abTrx2), an antibiotic resistant pathogenic superbug, is elucidated. By comparing Trx1 and Trx2, it is revealed that the two Trxs possess similar activity, although Trx2 contains an additional N-terminal zinc-finger domain and exhibits more flexible properties in solution. Finally, it is shown that the Trx2 zinc-finger domain might be rotatable and that proper zinc coordination at the zinc-finger domain is critical to abTrx2 activity. This study enhances understanding of the Trx system and will facilitate the design of novel antibiotics.

Bacterial sugar kinase is a central enzyme for proper sugar degradation in bacteria, essential for survival and growth. Therefore, this enzyme family is a primary target for antibacterial drug development, with YdjH most preferring to phosphorylate higher-order monosaccharides with a carboxylate terminus. Sugar kinases express diverse specificity and functions, making specificity determination of this family a prominent issue. This study examines the YdjH crystal structure from Acinetobacter baumannii (abYdjH), which has an exceptionally high antibiotic resistance and is considered a superbug. Our structural and biochemical study revealed that abYdjH has a widely open lid domain and is a solution dimer. In addition, the putative active site of abYdjH was determined based on structural analysis, sequence comparison, and in silico docking. Finally, we proposed the active site-forming residues that determine various sugar specificities from abYdjH. This study contributes towards a deeper understanding of the phosphorylation process and bacterial sugar metabolism of YdjH family to design the next-generation antibiotics for targeting A. baumannii. • The crystal structure of YdjH from a drug-resistant superbug was elucidated. • YdjH from Acinetobacter baumannii has a widely open lid domain and is a dimer in solution. • The putative active site of abYdjH was determined based on structural analysis, sequence comparison, and in silico docking. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance has already emerged as a major concern not only for public health but also for global economy. It causes a multifaceted crisis in development and growth by increasing the number of infections and deaths. Sustainable Development Goals are in place to ensure that development and growth are continual, as well as to end poverty, protect the environment, and promote peace and prosperity. In this review we tried to highlight the reasons for the prevalence of superbugs as well as their multifaceted impact on healthcare, and demonstrate potential ways to combat them and incorporate them into international policymaking processes. The literature review included articles from MEDLINE, EMBASE, Scopus, and PubMed published till the end of the year 2022 using keyword searches. Two hundred and forty-three research articles, review papers and studies written in English language evaluating the impact of Antimicrobial resistance (AMR) on patient, society and economy published until end of the year 2022 were included. Short conclusion: This review highlighted the significant impact of antimicrobial resistance (AMR) on the Sustainable Development Goals (SDGs) and was able to identify at least five SDGs that are linked to healthcare. The emergence of superbugs results in increased expenditure, which has serious consequences for the global economy, particularly in developing countries where infectious diseases are prevalent. The overuse and misuse of antibiotics, as well as poor infection control practices, are identified as primary drivers of superbug emergence. However, implementing strategies such as rational antibiotic use, effective infection control practices, and developing new antibiotics and alternative therapies can mitigate the adverse effects of AMR and contribute to achieving the SDGs. It is essential to integrate AMR strategies into national development plans and improve cross-sectoral collaboration among stakeholders to combat superbugs effectively. [ABSTRACT FROM AUTHOR]

COVID-19 showed the importance of trustworthy and accessible health information. News organisations increasingly introduced podcasting to keep their audiences informed. Podcasting's documented capacity for listener engagement makes it a pertinent medium to study another global public health threat – superbugs – through the lens of constructive journalism. Both constructive journalism and podcasting feature lived experiences of sources, in constructive journalism focused on empowering audiences to act. This practice-led research study is the first to explore how solutions-oriented journalism intersects with narrative podcasts. It demonstrates through the production of a podcast series about antimicrobial resistance (AMR), an affordance to tell complex and often scary health stories. It finds that podcasting can position individuals affected by AMR as sources of empowering information, rather than as victims. The study contributes new knowledge to constructive podcast journalism as an impactful approach in public health journalism, leveraging its potential to provide solutions to listeners and promote change. [ABSTRACT FROM AUTHOR]

IntroductionSalmonella enterica serovar Typhi (S. Typhi) is a major cause of morbidity and mortality in developing countries, contributing significantly to the global disease burden.MethodsIn this study, S. Typhi strains were isolated from 100 patients exhibiting symptoms of typhoid fever at a tertiary care hospital in Pakistan. Antimicrobial testing of all isolates was performed to determine the sensitivity and resistance pattern. Three MDR strains, namely QS194, QS430, and QS468, were subjected to whole genome sequencing for genomic characterization.Results and DiscussionMLST analysis showed that QS194, belonged to ST19, which is commonly associated with Salmonella enterica serovar typhimurium. In contrast, QS430 and QS468, belonged to ST1, a sequence type frequently associated with S. Typhi. PlasmidFinder identified the presence of IncFIB(S) and IncFII(S) plasmids in QS194, while IncQ1 was found in QS468. No plasmid was detected in QS430. CARD-based analysis showed that the strains were largely resistant to a variety of antibiotics and disinfecting agents/antiseptics, including fluoroquinolones, cephalosporins, monobactams, cephamycins, penams, phenicols, tetracyclines, rifamycins, aminoglycosides, etc. The S. Typhi strains possessed various virulence factors, such as Vi antigen, Agf/Csg, Bcf, Fim, Pef, etc. The sequencing data indicated that the strains had antibiotic resistance determinants and shared common virulence factors. Pangenome analysis of the selected S. Typhi strains identified 13,237 genes, with 3,611 being core genes, 2,093 shell genes, and 7,533 cloud genes. Genome-based typing and horizontal gene transfer analysis revealed that the strains had different evolutionary origins and may have adapted to distinct environments or host organisms. These findings provide important insights into the genetic characteristics of S. Typhi strains and their potential association with various ecological niches and host organisms.

Due to the overuse of antibiotics, bacterial resistance has markedly increased to become a global problem and a major threat to human health. Fortunately, in recent years, various new antibiotics have been developed through both improvements to traditional antibiotics and the discovery of antibiotics with novel mechanisms with the aim of addressing the decrease in the efficacy of traditional antibiotics. This manuscript reviews the antibiotics that have been approved for marketing in the last 20 years with an emphasis on the antibacterial properties, mechanisms, structure–activity relationships (SARs), and clinical safety of these antibiotics. Furthermore, the current deficiencies, opportunities for improvement, and prospects of antibiotics are thoroughly discussed to provide new insights for the design and development of safer and more potent antibiotics. [ABSTRACT FROM AUTHOR]

The increasing of drug-resistant bacteria and the scanty availability of novel effective antibacterial agents represent alarming problems of the modern society, which stimulated researchers to investigate novel strategies to replace or assist synthetic antibiotics. A great deal of attention has been devoted over the years to essential oils that contain mixtures of volatile compounds and have been traditionally exploited as antimicrobial remedies. Among the essential oil phytochemicals, remarkable antimicrobial and antibiotic-potentiating activities have been highlighted for cinnamaldehyde, an α,β-unsaturated aldehyde, particularly abundant in the essential oils of Cinnamomum spp., and widely used as a food additive in industrial products. In line with this evidence, in the present study, an overview of the available literature has been carried out in order to define the bacterial sensitizing profile of cinnamaldehyde. In vitro studies displayed the ability of the substance to resensitize microbial strains to drugs and increase the efficacy of different antibiotics, especially cefotaxime, ciprofloxacin, and gentamicin; however, in vivo, and clinical trials are lacking. Based on the collected findings, cinnamaldehyde appears to be of interest as an adjuvant agent to overcome superbug infections and antibiotic resistance; however, future more in-dept studies and clinical investigations should be encouraged to clarify its efficacy and the mechanisms involved. [ABSTRACT FROM AUTHOR]

Escherichia is a genus of prokaryotic gram-negative bacteria which forms a vital component of the gut microbiota of homeotherms including humans. Many members of this genus are commensals and pathogenic strains, which are responsible for some of the most common bacterial infections and can be fatal, particularly in the case of newborns and children. The fecal matter in wastewater treatment plants serves as major environmental sinks for the accumulation of Escherichia. The rise in antibiotic pollution and the lateral gene exchange of antibiotic-resistant genes have created antibiotic-resistant Escherichia strains that are often called superbugs. Antibiotic resistance has reached a crisis level that nowadays existing antibiotics are no longer effective. One way of tackling this emerging concern is by using nanomaterials. Punitively, nanomaterials can be used by conjugating with antibodies, biomolecules, and peptides to reduce antibiotic usage, whereas, preventatively, they can be used as either nano-antimicrobial additives or nano-photocatalytic sheets to reduce the microbial population and target the superbugs of environmental Escherichia. In this review, we have explored the threat posed by pathogenic Escherichia strains in the environment, especially in the context of antibiotic-resistant strains. Along with this, we have discussed some nanomaterial-mediated strategies in which the problem can be addressed by using nanomaterials as nanophotocatalytics, antimicrobial additives, drugs, and drug conjugates. This review also presents a brief overview of the ecological threats posed by the overuse of nanomaterials which warrants a balanced and judicious approach to the problem. [ABSTRACT FROM AUTHOR]

The emergence of pathogens is conferring resistance to last-resort therapies such as tigecycline, colistin, and carbapenems, limiting the therapeutic options, and raising concerns about the emergence of new "superbugs." This study reports the first incident of a blaNDM􀀀5 and tet(X4) co-harboring Escherichia coli with resistance to carbapenem and tigecycline recovered as the causative agent of a urinary tract infection in a 94-year-old patient. The E. coli strain ECCL209 carries multiple resistance genes [i.e., blaTEM􀀀1B, blaNDM􀀀5, blaCMY􀀀2, aadA22, florR, erm(B), mph(A), erm(42), lnuG, qnrS1, and sul2] and exhibits resistance to almost all clinically used antibiotics. MLST analysis found that the strain belongs to ST648, considered a worldwide highrisk pandemic clone. Moreover, multiple plasmid incompatibility types were detected, i.e., IncHI1A, IncHI1B, IncFII, IncFIA, IncFIB, IncQ1, Col, and IncX4. Genetic analysis revealed that blaNDM􀀀5 and tet(X4) genes were localized on two hybrid plasmids with multiple replicons. Continuous monitoring studies are suggested to quantify the antimicrobial resistance and assess the dissemination of such superbugs into a human healthcare setting. [ABSTRACT FROM AUTHOR]

Multidrug-resistant (MDR) superbugs can breach the blood–brain barrier (BBB), leading to a continuous barrage of pro-inflammatory modulators and induction of severe infection-related pathologies, including meningitis and brain abscess. Both broad-spectrum or species-specific antibiotics (β-lactamase inhibitors, polymyxins, vancomycin, meropenem, plazomicin, and sarecycline) and biocompatible poly (lactic-co-glycolic acid) (PLGA) nanoparticles have been used to treat these infections. However, new therapeutic platforms with a broad impact that do not exert off-target deleterious effects are needed. Membrane vesicles or extracellular vesicles (EVs) are lipid bilayer-enclosed particles with therapeutic potential owing to their ability to circumvent BBB constraints. Bacteria-derived EVs (bEVs) from gut microbiota are efficient transporters that can penetrate the central nervous system. In fact, bEVs can be remodeled via surface modification and CRISPR/Cas editing and, thus, represent a novel platform for conferring protection against infections breaching the BBB. Here, we discuss the latest scientific research related to gut microbiota- and probiotic-derived bEVs, and their therapeutic modifications, in terms of regulating neurotransmitters and inhibiting quorum sensing, for the treatment of neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases. We also emphasize the benefits of probiotic-derived bEVs to human health and propose a novel direction for the development of innovative heterologous expression systems to combat BBB-crossing pathogens. [ABSTRACT FROM AUTHOR]

Peptidoglycan digestion by murein-degrading enzymes is a critical process in bacterial cell growth and/or cell division. The membrane-bound lytic murein transglycosylase A (MltA) is a murein-degrading enzyme; it catalyzes the cleavage of the β-1,4-glycosidic linkage between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycans. Although substrate recognition and cleavage by MltA have been examined by previous structural and mutagenesis studies, the overall mechanism of MltA in conjunction with other functionally related molecules on the outer membrane of bacterial cells for peptidoglycan degradation has remained elusive. In this study, the crystal structure of MltA from the virulent human pathogen Acinetobacter baumannii is characterized and presented. The study indicated that MltA from A. baumannii forms homodimers via an extra domain which is specific to this species. Furthermore, the working mechanism of MltA with various functionally related proteins on the bacterial outer membrane was modeled based on the structural and biochemical analysis.

The emergence of pathogens is conferring resistance to last-resort therapies such as tigecycline, colistin, and carbapenems, limiting the therapeutic options, and raising concerns about the emergence of new “superbugs.” This study reports the first incident of a blaNDM–5 and tet(X4) co-harboring Escherichia coli with resistance to carbapenem and tigecycline recovered as the causative agent of a urinary tract infection in a 94-year-old patient. The E. coli strain ECCL209 carries multiple resistance genes [i.e., blaTEM–1B, blaNDM–5, blaCMY–2, aadA22, florR, erm(B), mph(A), erm(42), lnuG, qnrS1, and sul2] and exhibits resistance to almost all clinically used antibiotics. MLST analysis found that the strain belongs to ST648, considered a worldwide high-risk pandemic clone. Moreover, multiple plasmid incompatibility types were detected, i.e., IncHI1A, IncHI1B, IncFII, IncFIA, IncFIB, IncQ1, Col, and IncX4. Genetic analysis revealed that blaNDM–5 and tet(X4) genes were localized on two hybrid plasmids with multiple replicons. Continuous monitoring studies are suggested to quantify the antimicrobial resistance and assess the dissemination of such superbugs into a human healthcare setting.

Multidrug resistance in bacterial strains known as superbugs is estimated to cause fatal infections worldwide. Migration and urbanization have resulted in overcrowding and inadequate sanitation, contributing to a high risk of superbug infections within and between different communities. The CRISPR-Cas system, mainly type II, has been projected as a robust tool to precisely edit drug-resistant bacterial genomes to combat antibiotic-resistant bacterial strains effectively. To entirely opt for its potential, advanced development in the CRISPR-Cas system is needed to reduce toxicity and promote efficacy in gene-editing applications. This might involve base-editing techniques used to produce point mutations. These methods employ designed Cas9 variations, such as the adenine base editor (ABE) and the cytidine base editor (CBE), to directly edit single base pairs without causing DSBs. The CBE and ABE could change a target base pair into a different one (for example, G-C to A-T or C-G to A-T). In this review, we addressed the limitations of the CRISPR/Cas system and explored strategies for circumventing these limitations by applying diverse base-editing techniques. Furthermore, we also discussed recent research showcasing the ability of base editors to eliminate drug-resistant microbes.

Life-threatening diseases challenge immunity with a release of chromogranins. This report focuses on Chromogranin A (CGA) and some of its derived peptides in critically ill patients, with attention paid to their potential to become biomarkers of severity and actors of defense. First, we studied whether circulating CGA may be a biomarker of outcome in non-selected critically ill patients: CGA concentrations were reliably associated with short-term death, systemic inflammation, and multiple organ failure. Additionally, when studying Vasostatin-I, the major N-terminal fragment of CGA, we noted its reliable prognostic value as early as admission if associated with age and lactate. In trauma patients, CGA concentrations heralded the occurrence of care-related infections. This was associated with an in vitro inhibitor impact of Chromofungin on both NF-kappa B- and API-transcriptional activities. Secondly, in life-threatening disease-induced oxidative stress, the multimerization of Vasostatin-I occurs with the loss of its anti-microbial properties ex vivo. In vivo, a 4%-concentration of non-oxidized albumin infusion reversed multimerization with a decrease in care-related infections. Finally, in vitro Catestatin impacted the polymorphonuclear cells-Ca++-dependent, calmodulin–regulated iPLA2 pathway by releasing immunity-related proteins. Furthermore, human Cateslytin, the active domain of Catestatin, helped destroy S. aureus: this prompted the creation of synthetic D-stereoisomer of CGA-derived peptides against superbugs for the protection of implanted devices. In conclusion, CGA consideration in the critically ill is only starting, but it offers interesting perspectives for improved outcomes. [ABSTRACT FROM AUTHOR]

Superbugs are microorganisms that cause disease and have increased resistance to the treatments typically used against infections. Recently, antibiotic resistance development has been more rapid than the pace at which antibiotics are manufactured, leading to refractory infections. Scientists are concerned that a particularly virulent and lethal 'superbug' will one day join the ranks of existing bacteria that cause incurable diseases, resulting in a global health disaster on the scale of the Black Death. This study highlights the current developments in the management of antibiotic-resistant bacteria and recommends strategies for further regulating antibiotic-resistant microorganisms associated with the healthcare system. This review also addresses the origins, prevalence, and pathogenicity of superbugs, and the design of antibacterial against these growing multidrug-resistant organisms from a medical perspective. It is recommended that antimicrobial resistance should be addressed by limiting human-to-human transmission of resistant strains, lowering the use of broad-spectrum antibiotics, and developing novel antimicrobials. Using the risk-factor domains framework from this study would assure that not only clinical but also community and hospital-specific factors are covered, lowering the chance of confounders. Extensive subjective research is necessary to fully understand the underlying factors and uncover previously unexplored areas. [ABSTRACT FROM AUTHOR]

Lipid II, the main component of the bacterial cell wall, is synthesized by the addition of UDP-N-acetylglucosamine to the UDP-N-acetylmuramic acid pentapeptide catalyzed by the glycosyltransferase MurG. Owing to its critical role in cell-wall biosynthesis, MurG is considered to be an attractive target for antibacterial agents. Although the Mur family ligases have been extensively studied, the molecular mechanism of the oligomeric scaffolding assembly of MurG remains unclear. In this study, MurG from Acinetobacter baumannii (abMurG), a human pathogen, was characterized and its hexameric crystal structure was unveiled; this is the first homo-oligomeric structure to be described in the MurG family and the Mur family. Homogeneous protein samples were produced for structural studies using size-exclusion chromatography, the absolute molecular mass was calculated via multi-angle light scattering, and protein–protein interactions were analyzed using the PDBePISA server. abMurG was found to form homo-oligomeric complexes in solution, which might serve as functional units for the scaffolding activity of MurG. Furthermore, analysis of this structure revealed the molecular assembly mechanism of MurG. This structural and biochemical study elucidated the homo-oligomerization mechanism of MurG and suggests a new potential antibiotic target on MurG.

Thioredoxin (Trx) is a central component of the redox control system that maintains the redox homeostasis critical for organism survival. Owing to its central role in survival, Trx is a prospective target for novel antimicrobial agents. Herein, we report a 1.45 Å high-resolution structure of Trx1 of Acinetobacter baumannii (abTrx1), an antibiotic-resistant pathogenic superbug. Although abTrx1 exhibited the canonical Trx fold, which consists of a four-stranded β-sheet surrounded by four α-helices, structural differences were detected in the loop forming the C-X-X-C redox center and the C-terminal. The unique CAPC sequence of the C-X-X-C motif in the abTrx1 redox center was characterized by mutagenesis. This study contributes to the field of drug designing against superbugs. • The highest-resolution structure of Trx1 from a drug-resistant superbug was elucidated. • abTrx1 contains a unique structural feature. • Substitution of alanine in C-X-X-C motif with a bigger hydrophobic residue led to loss of abTrx1 activity. [ABSTRACT FROM AUTHOR]

Background: Respiratory infections are increasingly difficult to treat due to the emergence of multidrug-resistant bacteria. Rediscovery and implementation of inhaled bacteriophage (phage) therapy as a standalone or supplement to antibiotic therapy is becoming recognized as a promising solution to combating respiratory infections caused by these superbugs. To ensure maximum benefit of the treatment, phages must remain stable during formulation as a liquid or powder and delivery using a nebulizer or dry powder inhaler. Methods:Pseudomonas-targeting PEV phages were used as model phages to assess the feasibility of aerosolizing biologically viable liquid formulations using commercial nebulizers in the presence and absence of inhaled antibiotics. The advantages of powder formulations were exploited by spray drying to produce inhalable powders containing PEV phages with and without the antibiotic ciprofloxacin. Results: The produced phage PEV20 and PEV20–ciprofloxacin powders remained stable over long-term storage and exhibited significant bacterial killing activities in a mouse lung infection model. Conclusion: These studies demonstrated that inhaled phage (-antibiotic) therapy has the potential to tackle respiratory infections caused by superbugs. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance has emerged as a major global concern for public health in the last two decades, which tends to compromise the existing drug regimens in treating common or severe infections. According to WHO, three million laboratory-confirmed bacterial infections have been reported from 70 countries in 2019, caused by pathogens of concern. The drug-resistant bacterial strains are characterized as multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan drug-resistant (PDR) based on the different patterns of resistance. It is believed that novel strategies are essentially required to counter and eliminate drug resistance in a costeffective manner to benefit the world population. Natural compounds and certain dietary agents show potential antimicrobial properties and these have been used since ancient times to treat human infections. In this study, we have investigated the synergistic effects of dietary flavonoids rutin and quercetin with antibiotics gentamicin (an aminoglycoside) and ceftriaxone (a third-generation cephalosporin) against the drug-resistant superbugs; clinical isolates including Escherichia coli (MDR), Proteus mirabilis (XDR), and Klebsiella pneumoniae (PDR). Conventional MIC assay and checkerboard test were used as standard protocols. Our results show that rutin and quercetin restore the antimicrobial activity of the antibiotics against MDR and XDR strains, while no such effect was observed in the case of the PDR strain. Quercetin, which is a aglycone of flavonoid rutin, demonstrates higher synergistic effects with ceftriaxone compared to rutin. Since rutin and quercetin are essentially present in human diets as constituents of fruits and vegetables, their use as nutraceuticals in adjuvant therapies in combination with antibiotics against drug resistance is a promising therapeutic strategy against superbug infections. [ABSTRACT FROM AUTHOR]

Due to the overuse of antibiotics, bacterial resistance has markedly increased to become a global problem and a major threat to human health. Fortunately, in recent years, various new antibiotics have been developed through both improvements to traditional antibiotics and the discovery of antibiotics with novel mechanisms with the aim of addressing the decrease in the efficacy of traditional antibiotics. This manuscript reviews the antibiotics that have been approved for marketing in the last 20 years with an emphasis on the antibacterial properties, mechanisms, structure–activity relationships (SARs), and clinical safety of these antibiotics. Furthermore, the current deficiencies, opportunities for improvement, and prospects of antibiotics are thoroughly discussed to provide new insights for the design and development of safer and more potent antibiotics.

Bacterial evolution, particularly in hospital settings, is leading to an increase in multidrug resistance. Understanding the basis for this resistance is critical as it can drive discovery of new antibiotics while allowing the clinical use of known antibiotics to be optimized. Here, we report a photoactive chemical probe for superresolution microscopy that allows for the in situ probing of antibiotic-induced structural disruption of bacteria. Conjugation between a spiropyran (SP) and galactose via click chemistry produces an amphiphilic photochromic glycoprobe, which self-assembles into glycomicelles in water. The hydrophobic inner core of the glycomicelles allows encapsulation of antibiotics. Photoirradiation then serves to convert the SP to the corresponding merocyanine (MR) form. This results in micellar disassembly allowing for release of the antibiotic in an on-demand fashion. The glycomicelles of this study adhere selectively to the surface of a Gram-negative bacterium through multivalent sugar-lectin interaction. Antibiotic release from the glycomicelles then induces membrane collapse. This dynamic process can be imaged in situ by superresolution spectroscopy owing to the "fluorescence blinking" of the SP/MR photochromic pair. This research provides a high-precision imaging tool that may be used to visualize how antibiotics disrupt the structural integrity of bacteria in real time., Competing Interests: Competing interests statement:The authors declare no competing interest.

The need for novel antimicrobial agents in response to a growing antibiotic and antimicrobial resistance crisis is now at a breaking point. In this work, the use of 5 nm zinc oxide quantum dots (ZnO QDs), demonstrating rapid and high antimicrobial activity against Gram‐positive methicillin‐resistant Staphylococcus aureus and highly pathogenic yeast Candida auris cells under both non‐photocatalytic and photocatalytic conditions, is showcased. Results show ZnO QDs adhere and cluster around the microbial cell surfaces, and exhibit antimicrobial response toward attached cells, resulting in the cell membrane damage. With the introduction of ultraviolet‐A light, autogenous reactive oxygen species (ROS) are produced and caused further increase in cell membrane/wall disruption, in particular Gram‐negative Escherichia coli. Nanoscale Fourier transform infrared is used to further confirm the intrinsic biochemical changes that occur with the Gram‐negative cell membrane within 30 min and spectra demonstrate that biochemical alterations are achieved for the protein and carbohydrate component of the membrane, which is a common mechanism of ROS damage. Investigation of the cell membrane–material interaction and mechanism is crucial in developing and optimizing effective antimicrobial materials in combating the rise of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

The increasing of drug-resistant bacteria and the scanty availability of novel effective antibacterial agents represent alarming problems of the modern society, which stimulated researchers to investigate novel strategies to replace or assist synthetic antibiotics. A great deal of attention has been devoted over the years to essential oils that contain mixtures of volatile compounds and have been traditionally exploited as antimicrobial remedies. Among the essential oil phytochemicals, remarkable antimicrobial and antibiotic-potentiating activities have been highlighted for cinnamaldehyde, an α,β-unsaturated aldehyde, particularly abundant in the essential oils of Cinnamomum spp., and widely used as a food additive in industrial products. In line with this evidence, in the present study, an overview of the available literature has been carried out in order to define the bacterial sensitizing profile of cinnamaldehyde. In vitro studies displayed the ability of the substance to resensitize microbial strains to drugs and increase the efficacy of different antibiotics, especially cefotaxime, ciprofloxacin, and gentamicin; however, in vivo, and clinical trials are lacking. Based on the collected findings, cinnamaldehyde appears to be of interest as an adjuvant agent to overcome superbug infections and antibiotic resistance; however, future more in-dept studies and clinical investigations should be encouraged to clarify its efficacy and the mechanisms involved.

The occurrence and antibiogram profiles of Listeria monocytogenes in environmental waters in the Eastern Cape Province, South Africa, were investigated. Seventy-eight samples from rivers, wastewater, and irrigation water were collected at different geographical locations within the province from February to September 2019. The procedure of the International Organization for Standardization EN ISO 11290:2017 part 1 and 2 was adopted for the isolation of Lm. The counts of presumptive Lm ranged from 2.0 × 103 CFU/100 ml to 3.6 × 105 CFU/100 ml. About 39.74% of the samples were positive for Lm, and the isolates were confirmed as serotype 1/2a (78.95%) and serotype 4b (21.05%). About 68.42% of the isolates demonstrated biofilm-forming potentials. Ten virulence determinants including the plcA, inlA, and inlB were detected in all the isolates; however, inlC (85.97%), inlJ (80.70%), actA (59.65%), prfA (92.98%), plcB (89.47%), hly (80.70%), and mpl (73.68%) were less prevalent. The antibiogram profiles of confirmed Lm isolates revealed high susceptibilities (>50%) to all antibiotics ranging from 52.63% (cefotetan) to 100% (ampicillin) except for sulfamethoxazole (35.09%), erythromycin (26.32%), streptomycin (38.60%), oxytetracycline (45.61%), and amoxicillin (49.12%). Conversely, high resistance rates against sulfamethoxazole (63.16%), oxytetracycline (54.39%), and amoxicillin (50.88%) were observed. Isolates exhibited 52 resistance patterns against 22 antibiotics tested ranging from 1 to 15 antibiotics, and 82.46% showed multidrug-resistance phenotypes against the antibiotics. The antibiotic resistance index (ARI) of river water (0.18) was less than the permissible (0.2) Krumperman threshold, whereas that of irrigation and wastewater were higher than the Krumperman threshold. The multiple/antibiotic resistance index ((M)ARI) of each of the isolates ranged from 0.05–0.68. Resistance determinants (21) encoding resistance against sulphonamides, β-lactamase, phenicols, aminoglycosides, and tetracyclines were detected among the phenotypically resistant Lm isolates investigated which justifies the phenotypic resistance observed in this study. The abundance of resistance determinants in Lm recovered from environmental waters in this study suggests that the aquatic environments may serve as a channel for the dissemination of antimicrobial-resistant Lm to other niches including the food chain.

Bacteria often cause infections, and we take antibiotics to help us recover. Antibiotics are like magic pills that have saved millions of lives. However, the overuse of antibiotics is now making bacteria evolve fast and evade these antibiotics. A few bacteria like the purple one in the petri plate (Figure 1) have evolved a way to dodge and not get killed by one particular kind of antibiotic. The day might come soon when not a single antibiotic would work, and we could die of even tiny paper cuts. In this article, we discuss what antibiotics are, how they target bacteria, and why bacteria are suddenly becoming resistant to antibiotics. We include a list of ten points that each of us must follow and a pledge for everyone to take, to help stop the spread of antibiotic resistance. A small questionnaire is included that we would like you all to answer. Together we can win the battle against antibiotic resistance. [ABSTRACT FROM AUTHOR]

Thioredoxin reductase (TrxR) is a central component in the thioredoxin system by involving in catalyzing the reduction of thioredoxin, which is critical for organism survival. Because this system is essential, it is a promising target for novel antimicrobial agents. Herein, we solved the 1.9 Å high‐resolution structure of TrxR from Acinetobacter baumannii Thioredoxin reductase (AbTrxR), which is a Gram‐negative, pathogenic bacterium and a drug‐resistant superbug. AbTrxR was cofactor‐free and formed a dimer in solution. AbTrxR contained a longer dimerization loop2 and a shorter β7‐β8 connecting loop than other TrxRs. AbTrxR cofactor‐free form exhibited a flavin‐oxidizing (FO) conformation, whose NADPH domain was located close to the dimeric interface. This structural information might be helpful for development of new antibiotic agents targeting superbugs. [ABSTRACT FROM AUTHOR]