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Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

A green and facile method was proposed to prepare robust and fully bio-based modified paper in this study, which involved in layer-by-layer deposition of chitosan (CS) and mussel adhesive protein-mimetic polymer (dopamine-grafted carboxymethyl cellulose, CMC-g-DA) on paper surface and subsequent oxidative cross-linking by sodium periodate. The mechanical, barrier and antibacterial properties of the cross-linked multilayer-modified paper significantly improved with the increased bilayer numbers. Compared with unmodified paper, cross-linked (CS/CMC-g-DA)

Preservation of paper-based historical artifacts against deterioration due to the presence of bacteria and fungi colonies has been one of the major issues for the importance of protecting the cultural heritage of humankind. Advances in nanotechnology have enabled the implementation of nanomaterials for this purpose. In this work, calcium/chitosan nanoparticles (Ca/CS NPs) were prepared and well-characterized to investigate their potential as a novel approach for preserving paper-based documents. Following the fundamental characterizations, it was found that Ca/CS NPs are spherical nanoparticles with ~65 nm average size and homogenous dispersion (PdI: 0.2). Besides, minimum inhibition concentration results revealed that Ca/CS NPs show a superior antimicrobial effect against specific bacteria and fungi strains commonly found on paper documents compared to the effect of bare chitosan nanoparticles (CS NPs). After the deposition of Ca/CS NPs onto the paper the pH level was increased and stabilized, and only a limited amount of microbial colony formation was observed for up to 20 days. Moreover, molecular docking analysis provided a better insight into the antibacterial and antifungal activities of these nanoparticles. The antimicrobial activity of CS NPs and Ca/CS NPs was investigated through their interactions with E. coli DNA gyrase B and C. albicans dihydrofolate reductase. The binding modes and all possible interactions of active sites were confirmed by in silico molecular docking method. Collectively, our findings revealed that the formulated Ca/CS NPs are promising candidates for preserving paper documents.

Composite adsorbents based on metal-organic frameworks (MOFs) are excellent candidates for solid-phase extraction (SPE) due to their diverse chemical functionality and multilevel porosity. MOF superstructures based on self-assembly at room temperature (RT) could have less energy consumption and easier manipulation due to the larger complex geometry. The π-π stacking of the benzene ring could not only enhance the interaction toward hydrophobic or plane-structured targets but also be expected to promote the formation of the MOF superstructure. In this work, in the established RT self-assembly synthesis system, several factors were investigated to see how to obtain functional MOF superstructures with a regular geometry, among which the number of benzene rings in the ligand was mainly tested for its impact on self-assembly and adsorption capacity. By means of adsorption experiments and computational fluid dynamics (CFD) simulation, the relationship between structure and activity (SARs) was further explored. Interestingly, the MOF unit with the lowest specific surface area performed the best in adsorption. Then, the selected functional MOF superstructure and ionic liquid were used to produce the composite paper membrane facilely applied in the SPE device. After optimization of the preparation conditions and operation parameters, the established SPE-HPLC-UV method could selectively analyze tetracycline-like antibiotics in the range of 16.6-833.3 ng/g (ppb) in a meat sample. This work provided an RT synthesis method to produce a microsize MOF superstructure, with experimental and theoretical insights into the SARs, which could be expanded in the design of other MOF-based SPE composite membranes toward one group of analogues.

Infections caused by bacteria that produce β-lactamases (BLs) are a major problem in hospital settings. The phenotypic detection of these bacterial strains requires culturing samples prior to analysis. This procedure may take up to 72 h, and therefore it cannot be used to guide the administration of the first antibiotic regimen. Here, we propose a multisensor for identifying pathogens bearing different types of β-lactamases above the infectious dose threshold within 90 min that does not require culturing samples. Instead, bacterial cells are preconcentrated in the cellulose scaffold of a paper-based multisensor. Then, 12 assays are performed in parallel to identify whether the pathogens produce carbapenemases and/or cephalosporinases, including metallo-β-lactamases, extended-spectrum β-lactamases (ESBLs), and AmpC enzymes. The multisensor generates an array of colored spots that can be quantified with image processing software and whose interpretation leads to the detection of the different enzymes depending on their specificity toward the hydrolysis of certain antibiotics, and/or their pattern of inhibition or cofactor activation. The test was validated for the diagnosis of urinary tract infections. The inexpensive paper platform along with the uncomplicated colorimetric readout makes the proposed prototypes promising for developing fully automated platforms for streamlined clinical diagnosis.

This study reports the synthesis of bacterial cellulose (BC) hydrogel sheets and their utilization as a support for silver‑nickel oxide nanocomposites (Ag/NiO). A two-step facile hydrothermal method was employed for the preparation of Ag/NiO, followed by impregnation into BC hydrogel sheets. A 20% Ag/NiO composition was revealed by dry weight analysis. The stability of nanocomposites-Hydrogel was confirmed by Ag

The study's goal was to develop a spore-based paper strip biosensor for detecting ß-lactam antibiotics in milk using the enzyme induction principle. A new spore-based paper strip biosensor has been developed after important operating parameters such as spore volume, substrate volume, exposure time and temperature, and incubation time and temperature were optimised. The limit of detection for various ß-lactam antibiotics, including amoxicillin, penicillin, ampicillin, carbenicillin, cloxacillin, nafcillin, oxacillin, cephalothin, cefalexin, cefoxitin, cefazolin, and cefuroxime, was determined in milk with detection sensitivity of 1 ppb, 2 ppb, 2 ppb, 10 ppb, 10 ppb, 10 ppb, 20 ppb, 10 ppb 1000 ppb, 10 ppb 300 ppb and 100 ppb, respectively. It was also tested with other contaminants such non-ß-lactam antibiotics, pesticides, aflatoxin, heavy metals, and other chemical contaminants, and no interference was found, indicating that the created biosensor had a low rate of false positive and negative results. In comparison to the AOAC-approved CHARM-ROSA ß-lactam strip test, which identified 7 raw milk and zero pasteurised milk samples positive for ß-lactam antibiotics, the sensor was further analysed and verified using 200 raw milk and 105 pasteurised milk samples. This indicates a perfect match between our biosensor and the AOAC-approved CHARM-ROSA ß-lactam strip test. The developed spore-based paper strip biosensors are expected to be useful in the rapid and cost-effective detection of ß-lactam antibiotic residues in milk samples at the dairy farm, reception dock, and production units, respectively.

Antibiotic residues in the environment and in foods pose a serious threat to ecosystems and human health. Developing sensitive and on-site detection methods is therefore in high demand. In this work, a portable paper-based colorimetric sensor with a smartphone platform with an ultrahigh sensitivity has been designed for on-site and quantitative analysis of antibiotic residues based on aptamer-regulated nanozyme activity. The developed excellent peroxidase-like nanozymes, carbon-protected NiCo bimetal oxides with a unique hollow nanocage structure (NiCo@C HCs), could effectively catalyze the oxidation of chromogenic substrates by H

An enhanced ratiometric fluorescence sensor was built for on-site visual detection of doxycycline (DOX) through the interaction with bovine serum albumin on the surface of red emissive copper nanoclusters. Upon the addition of weakly fluorescent DOX, the red fluorescence from copper nanoclusters gradually decreased through the inner-filter effect (IFE), while a green fluorescence appears and significantly increases, forming an interesting fluorescent isosbestic point, which was assigned to DOX due to sensitization effect of bovine serum albumin. On the basis of this ratiometric fluorescence, the system possessed good limit of detection (LOD) of 45 nM and excellent selectivity for DOX over other tetracyclines. Based on these findings, a paper-based sensor has been fabricated for distinct visual detection of trace DOX and combined with smartphone color recognizer for quantitative detection of DOX (LOD = 83 nM). This method shows broad application prospects in environmental monitoring and food safety.

Pseudomonas aeruginosa is the most important opportunistic pathogen leading to serious and life-threatening infections, especially in immunocompromised patients. Because of its remarkable capacity to resist antibiotics, the selection of the right antibiotics with the exact dose for the appropriate duration is critical to effectively treat the infections and prevent antibiotic resistance. Although conventional genotypic and phenotypic antibiotic susceptibility testing (AST) methods have been dramatically advanced, they have suffered from many technical and operational issues as a generalized antibiotic stewardship program. Furthermore, given that most microbial infections are caused by their biofilms, the existing AST methods do not provide evidence-based antibiotic prescribing guidance for biofilm-based infections because the results are based on individual bacteria traditionally grown in their planktonic form. In this work, we create an innovative susceptibility testing technique for P. aeruginosa that offers clinically relevant guidelines and widely adaptable stewardship to effectively treat the infections and minimize antibiotic resistance. Our approach evaluates the antibiotic efficacy by continuously monitoring the accumulated electrical outputs from the bacterial extracellular electron transfer (EET) process in the presence of antibiotics. Our innovative paper-based culturing 3-D scaffold promotes surface-associated growth of bacterial colonies and biofilms. The platform replicates a natural habitat for P. aeruginosa where it can grow similarly to sites it infects. Our technique enables an all-electrical, real-time, easy-to-use, portable AST that can be easily translatable to clinical settings. The entire procedure takes 96 min to provide evidence-based antimicrobial prescribing guidance for biofilm-based infections.

Most technologies to produce multifunctional paper involved the defect of poor uniformity and stability. Herein, a high stability multi-functional cellulose-based paper was developed via a multiple chemical modification derived from waste bagasse. Firstly, the acetoacetyl groups was anchored on the surface of bagasse cellulose fibers by a heterogeneous transesterification. Then, paper was made based on these modified fibers. The fluorophore and gentamicin sulfate (Gen) were bonded in-situ to the paper through Hantzsch reaction and the form of enamine bond, respectively. The resulting paper exhibited excellent multifunctional properties, such as fluorescence property, antibacterial property and hydrophobic property. These properties are very stable to external environments. In addition, relatively mild surface modification has no obvious effect on fibers and shows similar whiteness and stiffness properties as that of the CAA paper. Thus, these novel functional papers held great potential for many fields such as food packaging, anti-counterfeiting, and other specialty papers.

Cellulosic paper has combined characteristics of renewability, biodegradability, flexibility, and recyclability. Based on disassembly-initiated fiber processing, the conversion of regular paper into a multifunctional wet-strength product was explored. In this concept, disassembly generates cellulosic additives for surface engineering. Encouragingly, the use of the aqueous solvent system containing mixed metal salts allows controllable fiber disassembly and formation of room-temperature-stable cellulosic solutions, leading to wet and dry strengthening of paper following cellulose regeneration. In-situ generation of cellulosic film-forming additives led to the increase of dry and wet strengths by more than 8 and 35 times respectively, in the case of a typical grade of quantitative filter paper. The engineered paper shows flame-retardant, antibacterial, and liquid-barrier features. The combination of functional properties of cellulosic paper can shed light on diversified applications, e.g., replacement of difficult-to-degrade synthetic plastics.

The increasing prevalence of antibiotic resistance threatens to make currently treatable bacterial diseases deadly again. As drug resistance rises, antibiotic susceptibility testing needs to adapt to allow for widespread, individualized testing. Paper-based diagnostics offer low-cost, disposable alternatives to traditional time consuming and costly in-house methods. Here, we describe a paper-based microfluidic device, called the Bac-PAC, capable of categorizing the antibiotic susceptibly of individual strains of Carbapenem-resistant Enterobacterales. Each chip provides a colored readout with actionable susceptibility classification of three antibiotics, thus maximizing the chances of identifying a viable therapy. We verified the technology on thirty bacterial strains with two dyes using six clinically relevant antibiotics. We demonstrated that the dried tests are stable for one month and can be incubated in a rechargeable coffee mug that reduces the need for external infrastructure.

In this work, the effect of using Ag-doped TiO

Infectious diseases triggered by bacteria cause a severe risk to human health. To counter this issue, surfaces coated with antibacterial materials have been widely used in daily life to kill these bacteria. The substrates enabled with a hybrid kill and release strategy can be employed not only to kill the bacteria but also to wash them using external stimuli (temperature, pH, etc.). Utilizing this concept, we develop thermoresponsive antibacterial-cellulose papers to exhibit hybrid kill and release properties. Thermoresponsive copolymers [p(NIPAAm

Bloodstream infection (BSI) is a major complication in patients with cancers due to therapy-induced neutropenia and underlying conditions, which increases hospitalization time and mortality rate. Targeted and timely antimicrobial management is crucial to save the patients’ lives and reduce the social and economic burdens. Blood culture is a routine clinical diagnostic method of BSI with a long turnaround time, and generally identifies monomicrobial BSI. Thus, polymicrobial BSI often goes undetected although it occurs more frequently in these patients and results in more severe outcomes compared to monomicrobial BSI. In this work, we apply glutaric anhydride, N-hydroxysuccinimide and N,N′-dicyclohexylcarbodiimide to fabricate a functional surface on cellulose filter paper. Targeting three pathogens (Escherichia coli, Saccharomyces cerevisiae, and human cytomegalovirus) commonly occurring in BSI in neutropenic patients, we demonstrate rapid and accurate triplex pathogen DNA detection using the functionalized paper. All three pathogen DNA was identified in 1–5 min with a detection limit of 0.1–0.5 ng/µL. The developed test tool has the potential to provide rapid polymicrobial BSI diagnosis in support of timely, accurate antimicrobial treatment, and could be integrated into an automatic sample-to-result portable equipment.

Antibiotics are used largely in agriculture and animal farming. As a result, antibiotic residues are found in food products as well as pharmaceutical industries and farming wastes. Since consumption of food products contaminated with antibiotic in excessive residuals causes severe environmental risks, our study here aims to detect the residues level of selected antibiotics in milk and egg. For monitoring of the antibiotic residues in various food diaries, low-cost, simple and rapid methods are required. This paper reports fabricating a disposable microfluidic paper-based analytical device for detection and discrimination of 8 antibiotics. This small but efficient device works based on combination of paper microfluidics, sensor array concept (an array of metallochromic complexes, which provides an optical tongue, and chemometrics data analysis. The discrimination is based on differential interaction of the antibiotics with 5 metal-indicator complexes and displacing the chromogenic indicators. This resulted in specific color changes for each antibiotic. The discriminant models obtained by employing linear discriminant analysis could discriminate antibiotics in real samples of milk and egg white and yolk at concentrations of as low as 5.0 mg L

Lanthanide coordination polymer nanoparticles (LML-Eu

Graphical abstract, Introduction Face masks are regarded as effective Personal Protective Equipment (PPE) during the COVID-19 pandemic. However, the dominant polypropylene (PP)-based masks are devoid of antiviral/antibacterial activities and create enormous environmental burdens after disposal. Objectives Here we report a facile and potentially scalable method to fabricate biodegradable, breathable, and biocidal cellulose nonwovens (BCNWs) to address both environmental and hygienic problems of commercially available face masks. Methods TEMPO-oxidized cellulose nonwovens are rendered antiviral/antibacterial via covalent bonding with disinfecting polyhexamethylene guanidine or neomycin sulfate through carbodiimide coupling chemistry. Results The obtained results showed that the BCNWs have virucidal rate of >99.14%, bactericidal efficiency of >99.51%, no leaching-out effect, and excellent air permeability of >1111.5 mm s−1. More importantly, the as-prepared BCNWs can inactivate SARS-CoV-2 instantly. Conclusions This strategy provides a new platform for the green fabrication of multifunctional cellulose nonwovens as scalable bio-protective layers with superior performance for various PPE in fighting COVID-19 or future pandemics. Additionally, replacing the non-biodegradable non-antimicrobial PP-based masks with the cellulose-based masks can reduce the plastic wastes and lower the greenhouse gas production from the incineration of disposed masks.

Many advanced technologies have shown encouraging results in removing antibiotics from domestic wastewater. However, as activated sludge treatment is the most common sewage treatment system employed worldwide, improving its effect on antibiotic removal would be more desirable. Understanding the removal mechanisms, kinetics and factors that affect antibiotic removal in the activated sludge process is important as it would allow us to improve the treatment performance. Although these have been discussed in various literature covering different types of antibiotics and wastewater, a specific review on antibiotics and domestic wastewater is clearly missing. This review paper collates, discusses and analyses the removal of antibiotics from sewage in the activated sludge process along with the removal mechanisms and kinetics. The antibiotics are categorised into six classes: β-lactam, dihydrofolate reductase inhibitor, fluoroquinolone, macrolide, sulfonamides and tetracycline. Furthermore, the factors affecting the system performance with regard to antibiotic removal are examined.

Phellinus Quél is one of the largest genera of Hymenochaetaceae; it comprises about 220 species widely distributed on Earth. Most Phellinus species are lignicolous mushrooms that accumulate bioactive compounds. This research studied the phenolic composition of Phellinus spp. and their relationship with antibacterial and antiviral capacity. Phenolics were extracted from Phellinus badius, P. fastuosus, and P. grenadensis; their antiviral and antibacterial activities were evaluated against Listeria monocytogenes, Staphylococcus aureus, Salmonella enterica, and Escherichia coli O157: H7; and the bacteriophages MS2 and Φ- × 174. Gallic acid, chlorogenic acid, caffeic acid, epicatechin, ferulic acid, catechin, 1,3-dicaffeoylquinic acid, p-coumaric acid, and rutin were found in different proportions among Phellinus spp. Total phenolic content ranged from 96 to 209 mg GAE/g, and total flavonoids from 10 to 27 QE/g. The minimum inhibitory concentrations of P. badius, P. grenadensis, and P. fastuosus against E. coli O157: H7 were 13, 20, and 27 mg/mL, against S. enterica were 20, 30, and 15 mg/mL, and against L. monocytogenes were 10, 15, and 25 mg/mL, respectively. The phenolic content was better correlated with the antibacterial effect against E. coli O157: H7 and L. monocytogenes (r = 0.8–0.9), but not against S. enterica (r = 0.05). The antiviral activity of the extracts (0.9 mg/mL) was 29 to 41% against MS2 and 27 to 38% for Φ-X174 virus (r = 0.8–0.9). In silico analysis showed binding energy values of − 7.9 and − 4.8 kcal/mol between the identified phenolic compounds and the M and G proteins of each virus. The antibacterial and antiviral properties of Phellinus species were correlated with the phenolic content.

Tuberculosis is a global health problem caused by infection with the Mycobacterium tuberculosis (Mtb) bacteria. Although antibiotic treatment has dramatically reduced the impact of tuberculosis on the population, the existence and spreading of drug resistant strains urgently demands the development of new drugs that target Mtb in a different manner than currently used antibiotics. The prokaryotic ubiquitin‐like protein (Pup) proteasome system is an attractive target for new drug development as it is unique to Mtb and related bacterial genera. Using a Pup‐based fluorogenic substrate, we screened for inhibitors of Dop, the Mtb depupylating protease, and identified I‐OMe‐Tyrphostin AG538 (1) and Tyrphostin AG538 (2). The hits were validated and determined to be fast‐reversible, non‐ATP competitive inhibitors. We synthesized >25 analogs of 1 and 2 and show that several of the synthesized compounds also inhibit the depupylation actions of Dop on native substrate, FabD‐Pup. Importantly, the pupylation activity of PafA, the sole Pup ligase in Mtb, was also inhibited by some of these compounds., The Mycobacterium tuberculosis (Mtb) prokaryotic ubiquitin‐like (pup) proteasome system is an attractive target for new drug development. In this study a screen was performed identifying Tyrphostins as low micromolar inhibitors of the Mtb protease Dop. To gain insight in the important functional aspects of these inhibitors, 25 new analogues were prepared and validated, in vitro. Several new compounds were able to inhibit both the depupylating activity of Dop as well as the pupylating activity of de pup ligase PafA.

Objective: To investigate the incidence and risk factors for liver abscess formation after treatment with drug-eluting bead chemoembolization (DEB-TACE) in patients with metastatic hepatic tumors (MHT). Methods: The current study is a retrospective analysis of the clinical data of 137 patients with metastatic hepatic tumors who received DEB-TACE treatment in our institute (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) between June 2015 and September 2020. Patients were evaluated for the presence or absence of post-DEB-TACE liver abscess. Univariate and multivariate analyses were used to identify risk factors for liver abscess formation. Results: The incidence of liver abscess formation after the DEB-TACE procedure was 8.76% per patient and 5.53% per procedure. Univariate analysis showed that larger maximum tumor diameter (p = 0.004), Grade 1 artery occlusion (p < 0.001) and systemic chemotherapy within 3 months before the DEB-TACE procedure (p < 0.001) were all associated with liver abscess formation. However, only systemic chemotherapy within 3 months before the DEB-TACE procedure (OR 5.49; 95% CI 0.34–13.54; p < 0.001) was identified by multivariate analysis to be an independent risk factor. Conclusions: Tumor size, Grade 1 artery occlusion and recent systemic chemotherapy may all be associated with increased risk of liver abscess formation following DEB-TACE treatment in patients with metastatic hepatic tumors. Advances in knowledge: Identification of risk factors for liver abscess formation following DEB-TACE in patients with MHT. These findings suggest the need for caution and consideration of the aforementioned risk factors on the part of interventional radiologists when designing DEB-TACE strategies and performing post-procedure patient management.

Population of drug-resistant bacteria have increased at an alarming rate in the past few decades. The major reason for increasing drug resistance is the lack of new antibiotics and limited drug targets. It has therefore been a vital task to develop new antibiotics with different drug targets. Two such targets are biofilm formation and quorum sensing. Quorum sensing is cell to cell communication used by bacteria that initiates many important survival processes and aids in establishing pathogenesis. Both biofilm and quorum sensing are inter-related processes and play a major role in physiological and pathogenesis processes. In this study, five novel imidazole derivatives (IMA-1–IMA-5) were synthesised and tested for their antibacterial and anti-quorum sensing activities against Chromobacterium violaceum using different in silico and in vitro techniques following the standard protocols. In silico results revealed that all compounds were able to effectively bind to and interact sufficiently with the target protein CviR. CviR is a protein to which autoinducers bind to initiate the quorum sensing process. In silico results also revealed that the compounds generated favourable structural dynamics implying that the compounds would be able to effectively bind to CviR and inhibit quorum sensing. Susceptibility results revealed that IMA-1 is the most active of all the derivatives against both planktonic cells and biofilms. Qualitative and quantitative evaluation of anti-quorum sensing activity at sub-inhibitory concentrations of these compounds also revealed high activity for IMA-1. Down-regulation of most of the quorum sensing genes when cells were treated with the test compounds affirmed the high anti-quorum sensing activities of these compounds. The results from this study are promising and urges on the use of anti-quorum sensing and biofilm disrupting molecules to combat multi-drug resistance problem. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42770-022-00702-8.

Pseudomonas aeruginosa is a gram-negative bacterium capable of forming persistent biofilms that are extremely difficult to eradicate. The species is most infamously known due to complications in cystic fibrosis patients. The high mortality of cystic fibrosis is caused by P. aeruginosa biofilms occurring in pathologically overly mucous lungs, which are the major cause facilitating the organ failure. Due to Pseudomonas biofilm-associated infections, remarkably high doses of antibiotics must be administered, eventually contributing to the development of antibiotic resistance. Nowadays, multidrug resistant P. aeruginosa is one of the most terrible threats in medicine, and the search for novel antimicrobial drugs is of the utmost importance. We have studied the effect of low molecular weight chitosan (LMWCH) on various stages of P. aeruginosa ATCC 10145 biofilm formation and eradication, as well as on production of other virulence factors. LMWCH is a well-known naturally occurring agent with a vast antimicrobial spectrum, which has already found application in various fields of medicine and industry. LMWCH at a concentration of 40 mg/L was able to completely prevent biofilm formation. At a concentration of 60 mg/L, this agent was capable to eradicate already formed biofilm in most studied times of addition (2–12 h of cultivation). LMWCH (50 mg/L) was also able to suppress pyocyanin production when added 2 and 4 h after cultivation. The treatment resulted in reduced formation of cell clusters. LMWCH was proved to be an effective antibiofilm agent worth further clinical research with the potential to become a novel drug for the treatment of P. aeruginosa infections. GRAPHICAL ABSTRACT: [Image: see text]

With the utilisation of algae, wastewater reuse is becoming a viable option for the energy industry, especially green energy. The growth of these algae in these wastewaters provides an alternative source for bioenergetics, however, the growth of other microorganisms can directly affect the production of bioenergy, requiring the removal and reduction of contaminants in these waters, in addition to being a source of contamination for workers. Therefore, the use of nanoparticles in bioremediation has been an alternative to mitigate the contamination of these wastewaters that have microorganisms capable of reducing the algae growth capacity. The objective of this work was to verify in the United States Patent and Trademarker office database (USPTO) patents that used chitosan nanoparticles as a form of wastewater treatment and to carry out the analysis of patent US20190134086, which addresses the use of zinc oxide nanoparticles associated with chitosan that was developed and used to evaluate their antibacterial activity against resistant microorganisms and biofilm producers present in wastewater. Escherichia coli, Enterococcus faecium, and/or Pseudomonas aeruginosa are the microorganisms involved in the evaluated invention, bacteria present in the gastrointestinal tract, of clinical and environmental importance. The synthesized nanoparticles are arranged as a pharmaceutically acceptable and toxic vehicle against resistant bacteria, thus being described as nanoremediators. Given the analyzed patent, it was possible to verify the importance of alternatives to reduce the impact that pollution, in general, has on the environment, in addition to the proposed technology serving to maintain the survival and development capacity of the algae that will be able to produce green energy, the nanoparticles with antibacterial potential can help indirectly reduce these pathogenic strains with resistance to several antibiotics in the environment.

Lactococcus spp. are industrially crucial lactic acid bacteria (LAB) used to manufacture lactic acid, pickled vegetables, buttermilk, cheese, and many kinds of delicious dairy foods and drinks. In addition to these, they are also being used as probiotics in specific formulations. However, their uses as probiotics are comparatively less than the other LAB genera. The present communication hypothesizes to validate the probiotic potentiality of two new Lactococcus lactis subsp. lactis strains for their future uses. These native food fermenting strains were characterized for in vitro acid tolerance, tolerance to simulated gastric and pancreatic juices, autoaggregation and co-aggregation, hydrophobicity, haemolytic activity, bile salt deconjugation, cholesterol removal, antimicrobial spectrum, and antibiotic sensitivity. The in vivo live bacterial feeding of these strains for 30 days was done in Swiss albino mice either singly or in combination with prebiotic inulin and evaluated for hypocholesterolemic activity, immune enhancement, and gut colonization efficiency and compared with the commercial probiotic consortia. The study revealed that the strains could survive in human gut bile concentration, gastric pH conditions at pH 2.0, 3.0, and 8.0 for 6 h, had a broad antibacterial spectrum, and cholesterol binding efficacy. The strains could survive with higher colony-forming units (CFU/mL) when amended with sodium caseinate. The strains had autoaggregation ranges from 15 to 25% over 24 h and had a significant co-aggregation with both lactic acid and Gram-positive and Gram-negative bacterial strains related to human illness. The strains also showed solvent and media-specific hydrophobicity against n-hexane and xylene. The live bacterial feeding either singly or in combination with prebiotic inulin resulted in a significant reduction of LDL (low-density lipoprotein), VLDL (very low-density lipoprotein) cholesterol and triglyceride (TG), and a significant increase in HDL (high-density lipoprotein) cholesterol level, and improved gut colonization and gut immunomodulation. The results prove that these non-haemolytic, non-toxic strains had significant health benefits than the commercial probiotics consortium with the recommended prebiotics mix. Thus, these new Lactococcus lactis subsp. lactis strains could be trialled as a new probiotic combination for human and animal feeds. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42770-022-00685-6.

Food-producing animals act as reservoirs of non-typhoidal Salmonella (NTS) serovars with potential food safety and public health implications. The present cross-sectional study aimed at determining the prevalence of Salmonella serotypes in non-diarrhoeic pigs and characterizing the isolates using molecular tools. Salmonella isolates (n = 22) recovered from faecal samples of 194 randomly selected pigs were characterized for virulence and antimicrobial resistance and subtyped using XbaI-PFGE. The prevalence of Salmonella in apparently healthy non-diarrhoeic pigs was 11.3% (95%CI, 4.3–19.5%), with S. Weltevreden (81.8%) and S. Enteritidis (18.2%) being the serotypes detected. Salmonella isolates harboured virulence genes such as invA (100%), stn (100%), spvR/spvC (86.3%) and fimA (22.7%). Phenotypically, isolates showed sensitivity to chloramphenicol, levofloxacin and ciprofloxacin and resistance to tetracycline and ampicillin (100%), streptomycin (86.4%), amoxicillin-clavulanate (63.6%), cefotaxime (22.7%) and ceftriaxone (9.1%). Notably, 18.2% isolates were multidrug-resistant (≥ 3 antimicrobial class) with multiple antimicrobial resistance (MAR) index of 0.56–0.67 (18.2%), 0.44 (45.5%), 0.33 (31.8%) and 0.22 (4.5%). Genotypically, isolates carried various antibiotic resistance genes: ESBL (bla(TEM) and bla(OXA)), aminoglycoside (strA, strB and aadA1), sulphonamide (sul1, sul2 and dfrA1), tetracycline (tetA and tetB) and plasmid AmpC beta-lactamase (ACC, FOX, MOX, DHA, CIT and EBC). The present investigation emphasizes the epidemiological significance of PFGE typing in the detection of emerging strains of highly virulent and multidrug-resistant S. Weltevreden and S. Enteritidis in non-diarrhoeic pigs that pose serious public health implications in the pork supply chain environment. More extensive longitudinal study is warranted to provide epidemiological links between environmental reservoirs and animal and human infections in piggery settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42770-022-00700-w.

BACKGROUND: Traditional culture-based microbiological methods remain the most used for defining the etiology of urinary tract infections and antibiotic susceptibility testing (AST) of isolated uropathogens. They are time-consuming and lead to delays of several days when obtaining the final results of microbiological tests. OBJECTIVES: In this study, we validate the possibility of using a microbiological CFN analyzer combined with MALDI-TOF mass spectrometry (MS) for fast conclusive urine testing (1 day) without obtaining pure cultures. MATERIALS AND METHODS: The study included three stages: detection of urine microflora growth using the CFN analyzer to separate positive and negative samples within 2–4 h; fast MS identification of positive samples without isolating uropathogens; fast AST using CFN analyzer within 3–6 h. In parallel, all urine samples were tested by traditional culture-based microbiological methods. RESULT: In total, 194 urine samples were tested, and 22 urine cultures were identified by MS, among them, 20 monocultures with bacterial counts ≥ 10(5) and 2 mixed cultures. The AST of these 22 urine cultures and additional 88 pure clinical cultures was performed using eight antibiotics. Overall, 276 tests were performed. The results of AST obtained using the CFN analyzer and traditional methods were in good agreement (98.2%). Although two mixed cultures were falsely identified as monocultures, their susceptibility determined by the CFN analyzer was correct. CONCLUSIONS: The CFN analyzer is promising and effective for fast AST. Combined with MS identification, it allows to perform full urine analysis in 1 day without the lengthy isolation of pure cultures.

The prevalence and risk factors for gut carriage of antimicrobial-resistant Escherichia coli among individuals living in the community in Rio de Janeiro, Brazil, are unknown. The aim of this study was to determine the prevalence of colonization with antimicrobial-resistant E. coli, including isolates producing ESBL and harboring plasmid-mediated quinolone resistant (PMQR) genes in this community. We performed a cross-sectional study and analyzed fecal specimens of individuals attending outpatient clinics in the city from January 2015 to July 2019. We investigated susceptibility to antimicrobial agents by disc diffusion tests and used PCR to determine ESBL types, PMQR, and the virulence genes that characterize an isolate as extraintestinal pathogenic E. coli (ExPEC). Among the 623 subjects, 212 (34%) carried an isolate resistant to at least one of the tested antimicrobial agents, with the highest frequencies of resistance to ampicillin (26%), trimethoprim-sulfamethoxazole (19%), cefazolin (14%), and ciprofloxacin (CIP, 9%). In addition, 13% (81) of subjects carried a multidrug-resistant-E. coli (MDR-E), including 47 (8% of all isolates) ESBL-producing E. coli (ESBL-E), mainly of CTX-M-8 (15, 32%) and CTX-M-15 (9, 20%) types. PMQR genes were present in 7% (42) of all isolates, including 60% (32) of the 53 resistant to CIP. Previous use of antimicrobial agents, particularly fluoroquinolones, was a risk factor for colonization with MDR-E (25%, 20/81 vs 13%, 70/542, p = 0.01), ESBL-E (28%, 13/47, vs 13%, 77/576, p = 0.01), and resistance to CIP (26%, 14/53, vs 12%, 70/570, p = 0.01). The most pathogenic phylogroups B2, C, and D were 37% of the MDR-E, 30% of the ESBL-E, 38% of the CIP-resistant, and 31% of PMQR gene carrying E. coli isolates. We show that carriage of MDR-E (mostly ESBL-E) reached high levels in the community in Rio de Janeiro, increased by the selection of antimicrobial agents. Much of the resistant E. coli isolates are potential pathogenic strains. The widespread use of antimicrobial agents during the COVID-19 pandemic in Brazil may have worsened this picture.

Banana (Musa acuminata) pseudostem cellulose was extracted and acetylated (CA) to prepare membranes with potential use as bio-packages. The CA membrane was embedded by Butia seed (CA-BS) or Butia pulp (CA-BP) extracts obtained from Butia catarinenses (Butia). The produced CA, CA-BS, and CA-BP membranes were evaluated for their physical-chemical, mechanical, thermal, and antibacterial properties. The process for obtaining the cellulose yielded a material with about 92.17% cellulose (DS = 2.85). The purity, cellulose degree acetylation, and the incorporation of Butia extracts into the membranes were confirmed by FTIR. The CA-BS and CA-BP membranes showed a smaller contact angle and higher swelling ratio than the CA membrane. Furthermore, Butia seed or pulp extracts reduced the elastic modulus and deformation at break compared to the CA membrane. The DSC analysis suggested the compatibility between sections and the CA matrix, whereas the TGA analysis confirmed the thermal stability of the membranes. Moreover, less than 1% of the Butia seed and pulp extracts were put into a food simulant media from the membrane. Finally, the CA-BS and CA-BP membranes could inhibit the growth of Staphylococcus aureus and Escherichia coli on their surface, confirming the potential use of these membranes as bio-packaging for food preservation.

Conditioning can drastically improve the dewaterability of sewage sludge and is widely practiced in most wastewater treatment plants (WWTPs). Sludge conditioning was also reported as a crucial step in sludge treatment to attenuate antibiotic resistance, but it remains unclear whether the attenuated antibiotic resistance by conditioning treatments would guarantee low abundance of antibiotic resistance genes (ARGs) in the compost products of municipal sewage sludge. Herein, the impacts of three conditioning treatments, including bioleaching and chemical conditioning using Fe[III]/CaO or polyacrylamide (PAM), on the abundances of 20 ARGs and 4 mobile genetic elements (MGEs) during conventional aerobic composting of dewatered sludge were investigated. It was found that the absolute and relative abundances of total ARGs in compost product of bioleached sludge accounted for only 13.8%-28.8% of that in compost products of un-conditioned, Fe[III]/CaO-conditioned, or PAM-conditioned sludges. Besides, bioleaching conditioning resulted in the lowest abundances of ARG subtypes and ARG-associated bacteria in the sludge compost product. The shift of ARG profiles in the bioleached sludge composting can be mainly ascribed to the ARG-associated bacteria, while the MGEs drove the ARG profiles during conventional composting of un-conditioned sludge and the two chemically conditioned sludge. Thus, bioleaching conditioning is superior to the chemical conditioning using Fe[III]/CaO or PAM in mitigating antibiotic resistance in sludge compost products, which was contributed by the pre-removal of ARGs prior to composting treatment and the potential limitation of ARGs transfer during conventional composting.

Traumatic brain injury (TBI) is one of the main concerns worldwide as there is still no comprehensive therapeutic intervention. Astrocytic water channel aquaporin-4 (AQP-4) system is closely related to the brain edema, water transport at blood-brain barrier (BBB) and astrocyte function in the central nervous system (CNS). Minocycline, a broad-spectrum semisynthetic tetracycline antibiotic, has shown anti-inflammation, anti-apoptotic, vascular protection and neuroprotective effects on TBI models. Here, we tried to further explore the underlying mechanism of minocycline treatment for TBI, especially the relationship of minocycline and AQP4 during TBI treatment. In present study, we observed that minocycline efficaciously reduces the elevation of AQP4 in TBI mice. Furthermore, minocycline significantly reduced neuronal apoptosis, ameliorated brain edema and BBB disruption after TBI. In addition, the expressions of tight junction protein and astrocyte morphology alteration were optimized by minocycline administration. Similar results were found after treating with TGN-020 (an inhibitor of AQP4) in TBI mice. Moreover, these effects were reversed by cyanamide (CYA) treatment, which notably upregulated AQP4 expression level in vivo. In primary cultured astrocytes, small-interfering RNA (siRNA) AQP4 treatment prevented glutamate-induced astrocyte swelling. To sum up, our study suggests that minocycline improves the functional recovery of TBI through reducing AQP4 level to optimize BBB integrity and astrocyte function, and highlights that the AQP4 may be an important therapeutic target during minocycline treating for TBI.

Antibiotic and antimicrobial resistance is a continually growing challenge in the treatment of various bacterial infections worldwide. New drugs and new drug targets are necessary to curb the threat of infectious diseases caused by multidrug-resistant pathogens. The tryptophan biosynthesis pathway is essential for bacterial growth but is absent in higher animals and humans. Drugs that can inhibit the bacterial biosynthesis of tryptophan offer a new class of antibiotics. In this work, we combined a structure-based strategy using in silico docking screening and molecular dynamics (MD) simulations to identify compounds targeting the α subunit of tryptophan synthase with experimental methods involving the whole-cell minimum inhibitory concentration (MIC) test, solution state NMR, and crystallography to confirm the inhibition of L-tryptophan biosynthesis. Screening 1800 compounds from the National Cancer Institute Diversity Set I against α subunit revealed 28 compounds for experimental validation; four of the 28 hit compounds showed promising activity in MIC testing. We performed solution state NMR experiments to demonstrate that Compound 1 binds to the α subunit. We also report a crystal structure of Salmonella enterica serotype Typhimurium tryptophan synthase in complex with one successful inhibitor, 3-amino-3-imino-2-phenyldiazenylpropanamide (Compound 1) which revealed a binding site at the αβ interface of the dimeric enzyme. MD simulations were carried out to examine two binding sites for the compound. Our results show that this small molecule inhibitor could be a promising lead for future drug development. This article is protected by copyright. All rights reserved.

The global emergence of antimicrobial resistance (AMR) has become a serious threat to human and animal health. Recent studies have shown that synanthropic animals can act as reservoirs and disseminators of pathogens and resistant bacteria. The aim of this study was to evaluate the frequency, distribution, and antimicrobial susceptibility of staphylococcal species and Clostridioides difficile isolated from the feces of free-living rodents and marsupials from two urban parks in Belo Horizonte, Brazil. During a 12-month period, fecal samples from 159 free-living animals, including 136 rodents and 23 marsupials, were collected from two urban parks in Belo Horizonte, Minas Gerais, Brazil. Staphylococcus spp. were more likely to be isolated from rodents than marsupials (p = 0.0164). Eight different staphylococcal species were isolated from 36 (26.5%) rodents and one marsupial (4.3%). S. saprophyticus (48.6%) was the most frequently isolated species, and almost a quarter of the isolates (24.3%) were resistant to at least one antimicrobial agent, four (10.8%) of which were multi-drug resistant (MDR). Two (5.4%) strains were resistant to cefoxitin and were then classified as methicillin-resistant staphylococci, and one also tested positive for the mecA gene. C. difficile was isolated from two rodents (1.5%), and one strain was toxigenic and classified as ribotype 064. One isolate was resistant to rifampicin, but both strains were susceptible to all other antimicrobials tested, including metronidazole and vancomycin. All C. difficile isolates and all staphylococcal strains resistant to antimicrobials were recovered from the same park. The present study suggests that free-living rodents in Belo Horizonte (Brazil) are mainly colonized by S. saprophyticus and may act as reservoirs of antimicrobial-resistant Staphylococcus spp. and C. difficile strains. This is the first study to evaluate the presence of staphylococci and C. difficile from free-living opossums and suggest a low fecal shedding of these organisms by these mammals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42770-021-00640-x.

Human skin banks around the world face a serious problem with the high number of allogeneic skins that are discarded and cannot be used for grafting due to persistent bacterial contamination even after antibiotic treatment. The biofilm formation capacity of these microorganisms may contribute to the antibiotic tolerance; however, this is not yet widely discussed in the literature. Thisstudy analyzed bacterial strains isolated from allogeneic human skin samples,which were obtained from a hospital skin bank that had already been discardeddue to microbial contamination. Biofilm formation and susceptibility topenicillin, tetracycline, and gentamicin were evaluated by crystal violetbiomass quantification and determination of the minimum inhibitoryconcentration (MIC), minimum biofilm inhibitory concentration (MBIC), andminimum biofilm eradication concentration (MBEC) by the broth microdilutionmethod with resazurin dye. A total of 216 bacterial strains were evaluated, and204 (94.45%) of them were classified as biofilm formers with varying degrees ofadhesion. MBICs were at least 512 times higher than MICs, and MBECs were atleast 512 times higher than MBICs. Thus, the presence of biofilm in allogeneicskin likely contributes to the inefficiency of the applied treatments as antibiotictolerance is known to be much higher when bacteria are in the biofilmconformation. Thus, antibiotic treatment protocols in skin banks shouldconsider biofilm formation and should include compounds with antibiofilmaction.

We investigated the antibacterial activity of the antimicrobial peptides h-Lf1-11, MSI-78, LL-37, fengycin 2B, and magainin-2. The minimum inhibitory concentration (MIC) was determined by microdilution technique according to CLSI (M07-A9, 2012) against Escherichia coli, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, carbapenem-resistant Klebsiella pneumoniae, and Acinetobacter baumannii. The MSI-78 showed potent bactericidal activity with MIC range of 1.25-40 mg/L against all bacterial strains. The h-Lf1-11, magainin-2, and LL-37 exhibited moderate activity (MIC range of 40-160, 80-160, and 40-160 mg/L, respectively) while the fengycin 2B did not show significant activity against all bacterial strains tested. These results revealed that MSI-78, h-Lf1-11, magainin-2, and LL-37 have great potential as antibacterial agents and their activity deserves to be more explored in further studies for the treatment of antibiotic-resistant bacteria.

Bacterial skin and soft tissue infections are among the most common bacterial infections and constitute a major burden for patients and healthcare systems. Care is complicated by the variety of potential pathogens, some with resistance to previously effective antimicrobial agents, the wide spectrum of clinical presentations and the risk of progression to life-threatening forms. More-efficient care pathways are needed that can reduce hospital admissions and length of stay, while maintaining a high quality of care and adhering to antimicrobial stewardship principles. Several agents approved recently for treating acute bacterial skin and skin structure infections have characteristics that meet these requirements. We address the clinical and pharmacological characteristics of the fourth-generation fluoroquinolone delafloxacin, and the long-acting lipoglycopeptide agents dalbavancin and oritavancin.

Purpose The purpose of this study is to better understand the prevalence of ototoxicity-related hearing loss and its functional impact on communication in a pediatric and young adult cohort with cystic fibrosis (CF) and individuals without CF (controls). Method We did an observational, cross-sectional investigation of hearing function in children, teens, and young adults with CF ( n = 57, M = 15.0 years) who received intravenous aminoglycoside antibiotics and age- and gender-matched controls ( n = 61, M = 14.6 years). Participants completed standard and extended high-frequency audiometry, middle ear measures, speech perception tests, and a hearing and balance questionnaire. Results Individuals with CF were 3–4 times more likely to report issues with hearing, balance, and tinnitus and performed significantly poorer on speech perception tasks compared to controls. A higher prevalence of hearing loss was observed in individuals with CF (57%) compared to controls (37%). CF and control groups had similar proportions of slight and mild hearing losses; however, individuals with CF were 7.6 times more likely to have moderate and greater degrees of hearing loss. Older participants displayed higher average extended high-frequency thresholds, with no effect of age on average standard frequency thresholds. Although middle ear dysfunction has not previously been reported to be more prevalent in CF, this study showed that 16% had conductive or mixed hearing loss and higher rates of previous otitis media and pressure equalization tube surgeries compared to controls. Conclusions Individuals with CF have a higher prevalence of conductive, mixed, and sensorineural hearing loss; poorer speech-in-noise performance; and higher rates of multiple symptoms associated with otologic disorders (tinnitus, hearing difficulty, dizziness, imbalance, and otitis media) compared to controls. Accordingly, children with CF should be asked about these symptoms and receive baseline hearing assessment(s) prior to treatment with potentially ototoxic medications and at regular intervals thereafter in order to provide otologic and audiologic treatment for hearing- and ear-related problems to improve communication functioning.

Objective The study objective of this analysis was to determine the cost-effectiveness of vaborem (meropenem-vaborbactam) compared to the best available therapy (BAT) in adult patients with carbapenem-resistant Enterobacteriaceae—Klebsiella pneumoniae carbapenemase (CRE-KPC) infections from the perspective of the UK National Health Service (NHS) and Personal Social Services (PSS). Methods A decision tree model was developed to conduct a cost-effectiveness analysis for Vaborem compared to BAT in CRE-KPC patients over a 5 year time horizon. The model structure for Vaborem simulated the clinical pathway of patients with a confirmed CRE-KPC infection. Model inputs for clinical effectiveness were sourced from the TANGO II trial, and published literature. Costs, resource use and utility values associated with CRE-KPC infections in the UK were sourced from the British National Formulary, NHS reference costs and published sources. Results Over a 5 year time horizon, Vaborem use increased total costs by £5165 and increased quality-adjusted life years (QALYs) by 0.366, resulting in an incremental cost-effectiveness ratio (ICER) of £14,113 per QALY gained. The ICER was most sensitive to the probability of discharge to long-term care (LTC), the annual cost of LTC and the utility of discharge to home. At thresholds of £20,000/QALY and £30,000/QALY, the probability of Vaborem being cost-effective compared to BAT was 79.85% and 94.93%, respectively. Conclusion Due to a limited cost impact and increase in patient quality of life, vaborem can be considered as a cost-effective treatment option compared to BAT for adult patients with CRE-KPC infections in the UK.

In recent years, veterinary probiotic formulations constitute an interesting alternative to the use of antibiotics in animals for human consumption, but beneficial microorganisms must meet certain requirements to be included in these products. The objective of this work was to evaluate the safety and innocuity of beneficial autochthonous lactic bacteria (BALB) as well as to determine their beneficial, environmental, and technological characterization. Antibiotic resistance was assayed using phenotypic and genotypic methodology. A bovine vaginal fluid simulated medium (MSBVF) was designed where growth, pH changes, and expression of beneficial characteristics of lactic bacteria were evaluated; additionally, the optimal culture conditions in commercial media were determined in order to obtain the highest biomass production of the strains. Finally, the best strains were lyophilized and administered intravaginally to pregnant cows and their permanence in the vagina and adverse effects were evaluated. The results show that most of the strains were resistant to vancomycin, tetracycline, and streptomycin, with a high sensitivity to ampicillin, gentamicin, and clindamycin. The strains evaluated did not show gelatinase or hyaluronidase activity; however, 11 strains produced α-type hemolysis. The optimal growth of the microorganism was obtained in MRS broth, under slight agitation and without pH control. The strains grown in the MSBVF grew well and maintained the probiotic properties. Animals treated with probiotics bacteria did not show systemic or local inflammation. These strains can be included in a probiotic veterinary product to be applied to different bovine mucosa.

Antimicrobial resistance (AMR) is currently discussed as an important issue worldwide, and the presence of antimicrobial residues (ARs) and antimicrobial resistance genes (ARGs) in the environment, especially in the water sources, is a challenge for public health. This study was conducted to evaluate the occurrence and diversity of AR and ARG in water sources from an urban center, in Southern Brazil. A total of thirty-two water samples from drinking water treatment plants (24) and sewage systems (8) were collected during two annual samplings, winter and summer. The PCR was performed by 18 ARGs, and the detection of 47 ARs was performed by LC–MS/MS. All sewage samples presented carbapenemases, ESBL, and mcr-1 genes as well as quinolones and sulfamethoxazole residues. In drinking water, we just detected bla(TEM) and tetB genes and doxycycline residues in samples before treatment. This study provides data about AR and ARG in drinking water and sewage systems showing that these sources are important reservoirs of both. The limited effectiveness of wastewater treatment processes to remove mainly AR demonstrates the need to implement better protocols of disinfection, in order to limit the spread of AMR in the environment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42770-022-00786-2.

In Staphylococcus aureus, vancomycin‐resistance‐associated response regulator (VraR) is a part of the VraSR two‐component system, which is responsible for activating a cell wall‐stress stimulon in response to an antibiotic that inhibits cell wall formation. Two VraR‐binding sites have been identified: R1 and R2 in the vraSR operon control region. However, the binding of VraR to a promoter DNA enhancing downstream gene expression remains unclear. VraR contains a conserved N‐terminal receiver domain (VraR(N)) connected to a C‐terminal DNA binding domain (VraR(C)) with a flexible linker. Here, we present the crystal structure of VraR(C) alone and in complex with R1‐DNA in 1.87‐ and 2.0‐Å resolution, respectively. VraR(C) consisting of four α‐helices forms a dimer when interacting with R1‐DNA. In the VraR(C)–DNA complex structure, Mg(2+) ion is bound to Asp194. Biolayer interferometry experiments revealed that the addition of Mg(2+) to VraR(C) enhanced its DNA binding affinity by eightfold. In addition, interpretation of NMR titrations between VraR(C) with R1‐ and R2‐DNA revealed the essential residues that might play a crucial role in interacting with DNA of the vraSR operon. The structural information could help in designing and screening potential therapeutics/inhibitors to deal with antibiotic‐resistant S. aureus via targeting VraR.

Acute intestinal mucositis is a common off-target effect of chemotherapy, leading to co-morbidities such as vomiting, diarrhea, sepsis, and death. We previously demonstrated that the presence of enteric bacteria modulates the extent of jejunal epithelial damage induced by doxorubicin (DXR) in mice. Despite conventional thinking of the crypt as a sterile environment, recent evidence suggests that bacterial signaling influences aISC function. In this study, we labeled aISCs using transgenic Lgr5-driven fluorescence or with immunostaining for OLFM4. We examined the effect of DXR in both germ free (GF) mice and mice depleted of microbiota using an established antimicrobial treatment protocol (AMBx). We found differences in DXR-induced loss of aISCs between GF mice and mice treated with AMBx. aISCs were decreased after DXR in GF mice, whereas AMBx mice retained aISC expression after DXR. Neither group of mice exhibited an inflammatory response to DXR, suggesting the difference in aISC retention was not due to differences in local tissue inflammation. Therefore, we suspected that there was a protective microbial signal present in the AMBx mice that was not present in the GF mice. 16S rRNA sequencing of jejunal luminal contents demonstrated that AMBx altered the fecal and jejunal microbiota. In the jejunal contents, AMBx mice had increased abundance of Ureaplasma and Burkholderia. These results suggest pro-survival signaling from microbiota in AMBx-treated mice to the aISCs, and that this signaling maintains aISCs in the face of chemotherapeutic injury. Manipulation of the enteric microbiota presents a therapeutic target for reducing the severity of chemotherapy-associated mucositis.

The emergence and worldwide spread of Methicillin-resistant Staphylococcus aureus (MRSA) pose a threat to human health. While bacteriophages are recognized as an effective alternative to treat infections caused by drug resistant pathogens, some bacteriophages in particular the temperate bacteriophage may also influence the virulence of the host bacteria in distinct ways. In this study, we isolated a bacteriophage vB_Saus_PHB21 from an epidermal sample of Siberian tiger (Panthera tigris altaica) using an MRSA strain SA14 as the indicator. Our following laboratory tests and whole genome sequencing analyses revealed that vB_Saus_PHB21 was a temperate bacteriophage belonging to the Siphoviridae family, and this bacteriophage did not contain any virulence genes. However, the integration of PHB21 genome into the host MRSA increased the bacterial capacities of cell adhesion, anti-phagocytosis, and biofilm formation. Challenge of the lysogenic strain (SA14+) caused severe mortalities in both Galleria mellonella and mouse models. Mice challenged with SA14+ showed more serious organ lesions and produced higher inflammatory cytokines (IL-8, IFN-γ and TNF-α) compared to those challenged with SA14. In mechanism, we found the integration of PHB21 genome caused the upregulated expression of many genes encoding products involved in bacterial biofilm formation, adherence to host cells, anti-phagocytosis, and virulence. This study may provide novel knowledge of “bacteria-phage-interactions” in MRSA.

Lipopolysaccharide (LPS) is an essential structural component of the outer membrane (OM) of most Gram-negative bacteria. In the model organism Escherichia coli, LPS transport to the OM requires seven essential proteins (LptABCDEFG) that form a continuous bridge across the cell envelope. In Pseudomonas aeruginosa the recently-demonstrated essentiality of LptD and LptH, the P. aeruginosa LptA homologue, confirmed the crucial role of the Lpt system and, thus, of LPS in OM biogenesis in this species. Surprisingly, independent high-throughput transposon mutagenesis studies identified viable P. aeruginosa insertion mutants in the lptE gene, suggesting that it might be dispensable for bacterial growth. To test this hypothesis, we generated an lptE conditional mutant in P. aeruginosa PAO1. LptE depletion only slightly impairs P. aeruginosa growth in vitro. Conversely, LptE is important for cell envelope stability, antibiotic resistance and virulence in an insect model. Interestingly, the maturation and OM localization of LPS is only marginally affected in LptE-depleted cells, while the levels of the OM component LptD are strongly reduced. This suggests that P. aeruginosa LptE might not be directly involved in LPS transport, although it is clearly essential for the maturation and/or stability of LptD. While poor functionality of LptD caused by LptE depletion is somehow tolerated by P. aeruginosa, this has a high cost in terms of cell integrity, drug resistance and virulence, highlighting LptE function(s) as an interesting target to weaken P. aeruginosa defenses and reduce its infectivity.

Pyrroles and its fused forms possess antimicrobial activities, they can easily interact with biomolecules of living systems. A series of substituted pyrroles, and its fused pyrimidines and triazines forms have been synthesised, all newly synthesised compound structures were confirmed by spectroscopic analysis. Generally, the compounds inhibited growth of some important human pathogens, the best effect was given by: 2a, 3c, 4d on Gram-positive bacteria and was higher on yeast (C. albicans), by 5c on Gram-negative bacteria and by 5a then 3c on filamentous fungi (A. fumigatus and F. oxysporum). Such results present good antibacterial and antifungal potential candidates to help overcome the global problem of antibiotic resistance and opportunistic infections outbreak. Compound 3c gave the best anti-phytopathogenic effect at a 50-fold lower concentration than Kocide 2000, introducing a safe commercial candidate for agricultural use. The effect of the compounds on DNA was monitored to detect the mode of action.

In a bioprospecting study of paramo soils cultivated with potato (Solanum tuberosum), 50 fungal isolates were obtained and evaluated for their nitrate reductase (NR) activity, given the role played by this enzyme in the biosynthesis of silver nanoparticles (AgNps). Five isolates strain with high NR activity belonging to Penicillium simplicissimum, Aspergillus niger, and Fusarium oxysporum species were selected, verifying the presence of the NR enzyme in their enzymatic extract. Later, these strains showed the ability to biosynthesize AgNps with distorted spherical shapes and sizes ranging from 15 to 45 nm. Subsequently, an antibiosis test was carried out by the agar diffusion method using glass fiber disks against the phytopathogenic agent Pectobacterium carotovorum, finding halos of inhibition of bacterial growth up to 15.3 mm using a 100 ppm solution of the AgNps obtained from F. oxysporum. These results contribute to generating the basis of a new alternative for the control of this phytopathogenic agent of potato, challenging to manage by traditional methods and of relevance at the post-harvest level.

Neisseria gonorrhoeae is a high-priority pathogen of concern due to the growing prevalence of resistance development against approved antibiotics. Herein, we report the anti-gonococcal activity of ethoxzolamide, the FDA-approved human carbonic anhydrase inhibitor. Ethoxzolamide displayed an MIC50, against a panel of N. gonorrhoeae isolates, of 0.125 µg/mL, 16-fold more potent than acetazolamide, although both molecules exhibited almost similar potency against the gonococcal carbonic anhydrase enzyme (NgCA) in vitro. Acetazolamide displayed an inhibition constant (Ki) versus NgCA of 74 nM, while Ethoxzolamide’s Ki was estimated to 94 nM. Therefore, the increased anti-gonococcal potency of ethoxzolamide was attributed to its increased permeability in N. gonorrhoeae as compared to that of acetazolamide. Both drugs demonstrated bacteriostatic activity against N. gonorrhoeae, exhibited post-antibiotic effects up to 10 hours, and resistance was not observed against both. Taken together, these results indicate that acetazolamide and ethoxzolamide warrant further investigation for translation into effective anti-N. gonorrhoeae agents.