Antimicrobial Drug Resistance Research Articles

Epidemiology and Management of Infections in Liver Transplant Recipients.

Background: Improvements in liver transplant (LT) outcomes are attributed to advances in surgical techniques, use of potent immunosuppressants, and rigorous pre-LT testing. Despite these improvements, post-LT infections remain the most common complication in this population. Bacteria constitute the most common infectious agents, while fungal and viral infections are also frequently encountered. Multi-drug-resistant bacterial infections develop because of polymicrobial overuse and prolonged hospital stays. Immediate post-LT infections are commonly caused by viruses. Conclusions: Appropriate vaccination, screening of both donor and recipients before LT and antiviral prophylaxis in high-risk individuals are recommended. Antimicrobial drug resistance is common in high-risk LT and associated with poor outcomes; epidemiology and management of these cases is discussed. Additionally, we also discuss the effect of coronavirus disease 2019 (COVID-19) infection and monkeypox in the LT population.

Imidazooxazine moiety as polyketide synthase 13 inhibitors targeting tuberculosis

IntroductionRecently, imidazooxazineshave attracted more attention due to their therapeutic potential against tuberculosis (TB). The present study aimed to identify and develop potential inhibitors against Pks13-TE to combat the antimicrobial drug resistance of TB. MethodsComputer-aided drug design is a more highly valued technology than the traditional drug discovery approach. Herein, we computationally investigated a chemical dataset using QSAR models and virtually screened novel leads of imidazooxazines against the thioesterase domain, further subjecting them to molecular docking and dynamics simulation. ResultsThe present study identified two molecules, 1 and 3, promising leads with minimum energy conformations of −7.63 and −7.62 kcal, respectively, providing structural insight into Pks13 inhibition. The average values of MolSA, SASA, and PSA for molecules 1 and 3 were 382.41 Å, 77.65 Å, and 195.54 Å and 386.24 Å, 71.105 Å, and 184.46 Å, respectively. In conclusion, our research has demonstrated that imidazoxazines are promising leads to combat the resistance problem of TB. Among the two potent molecules 1 and 3, molecule 1 displayed favourable interactions in the active site with good stability, as confirmed by the RMSD, RMSF, RoG, H-bond, and SASA analyses. The Molecule 1 protein complex showed two strong hydrogen bonds, effectively maintained for 80–85 % of the simulation time, indicating its stability and potency. ConclusionThe identified two molecules and their conformations were highly stable; hence, these findings provide valuable insight into the evolution of new therapeutic agents to address the growing problem of TB and its resistance.

Quantum biochemical analysis of the TtgR regulator and effectors

The recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs by numerous mechanisms, active efflux of the drugs is a critical concern. A single species of efflux pump can produce a simultaneous resistance to several drugs. One of the best-studied efflux pumps is the TtgABC: a tripartite resistance-nodulation-division (RND) efflux pump implicated in the intrinsic antibiotic resistance in Pseudomonas putida DOT-T1E. The expression of the TtgABC gene is down-regulated by the HTH-type transcriptional repressor TtgR. In this context, by employing quantum chemistry methods based on the Density Functional Theory (DFT) within the Molecular Fragmentation with Conjugate Caps (MFCC) approach, we investigate the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two broad-spectrum antimicrobial agents. Our quantum biochemical computational results show the: [i] convergence radius, [ii] total binding energy, [iii] relevance (energetically) of the ligands regions, and [iv] most relevant amino acids residues of the TtgR-QUE/TAC/CLM complexes, pointing out distinctions and similarities among them. These findings improve the understanding of the binding mechanism of effectors and facilitate the development of new chemicals targeting TtgR, helping in the battle against the rise of resistance to antimicrobial drugs. These advances are crucial in the ongoing fight against rising antimicrobial drug resistance, providing hope for a future where healthcare-associated infections can be more beneficially treated.

Characterization of four peptides from milk fermented with kombucha cultures and their metal complexes-in search of new biotherapeutics.

The most common skin diseases include eczema, psoriasis, acne, and fungal infections. There is often no effective cure for them. Increasing antimicrobial drug resistance prompts us to search for new, safe, and effective therapeutics. Among such interesting candidates are peptides derived from milk fermented with specific lactic acid bacteria or with kombucha cultures, which are a potential treasure trove of bioactive peptides. Four of them are discussed in this article. Their interactions with zinc and copper ions, which are known to improve the well-being of the skin, were characterized by potentiometry, MS, ITC, and spectroscopic methods, and their cytostatic potential was analyzed. The results suggest that they are safe for human cells and can be used alone or in complexes with copper for further testing as potential therapeutics for skin diseases.

Extracellular Vesicles: Translational Agenda Questions forThree Protozoan Parasites.

The protozoan parasites Plasmodium falciparum, Leishmania spp. and Trypanosoma cruzi continue to exert a significant toll onthe disease landscape of the human population in sub-Saharan Africa and Latin America. Control measures have helped reduce the burden of their respective diseases-malaria, leishmaniasis and Chagas disease-in endemic regions. However, the need for new drugs, innovative vaccination strategies and molecular markers of disease severity and outcomes has emerged because of developing antimicrobial drug resistance, comparatively inadequate or absent vaccines, and a lack of trustworthy markers of morbid outcomes. Extracellular vesicles (EVs) have been widely reported to play a role in the biology and pathogenicity of P. falciparum, Leishmania spp. and T. cruzi ever since they were discovered. EVs are secreted by a yet to be fully understood mechanism in protozoans into the extracellular milieu and carry a cargo of diverse molecules that reflect the originator cell's metabolic state. Although our understanding of the biogenesis and function of EVs continues to deepen, the question of how EVs in P. falciparum, Leishmania spp. and T. cruzi can serve as targets for a translational agenda into clinical and public health interventions is yet to be fully explored. Here, as a consortium of protozoan researchers, we outline a plan for future researchers and pose three questions to direct an EV's translational agenda in P. falciparum, Leishmania spp. and T. cruzi. We opine that in the long term, executing this blueprint will help bridge the current unmet needs of these medically important protozoan diseases in sub-Saharan Africa and Latin America.

Green Synthesis of Molybdenum Nanoparticles From Solanum xanthocarpum and Evaluation of Their Antimicrobial and Antioxidant Activity Against Multidrug-Resistant Wound Isolates.

In recent years, antimicrobial drug resistance has emerged as a serious global public health concern, according to the World Health Organization data. The emergence of pathogens resistant to multiple drugs has been linked to an increase in morbidity and mortality from microbial infections. The study's main goal is to explore the efficacy of using Solanum xanthocarpum in the green synthesisof molybdenum nanoparticles (Mo NPs) for antibacterial and antioxidant properties. An eco-friendly method of synthesizing Mo NPswas accomplished using an aqueous extract of Solanum xanthocarpum. Characterization of the synthesized nanoparticles was done by UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FT-IR),X-ray diffraction (XRD), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX). After that,antibacterial and antioxidant activity was further evaluated. The UV-visible spectrophotometer analysis confirmed the presence of synthesized Mo NPs showing a peak around 320 nm. The presence of functional compounds like C-CI, C-H, C=C, and O=C=O was confirmed by FT-IR spectrum analysis. The positions of diffraction peaks in Mo NPpatterns were identified using XRD analysis; they were more crystalline (82.7%) and less amorphous (17.3%). The presence of the elements molybdenum (Mo), carbon (C), and oxygen (O) was confirmed by the EDX spectrum and irregular shapesshown in the SEM images. Further, the antimicrobial study results showed the formation of an inhibition zone against 27 mm for Klebsiella pneumoniae, 24 mm for Pseudomonas aeruginosa, 22 mm for Staphylococcus aureus, and 24 mm for Enterococcus faecalis,respectively, at a high concentration 80 μg/ml of Mo NPs. The maximum antioxidant activity at 100 μg/ml was 73.49%, compared to the standard ascorbic acid (74.25%). Additionally, the moderate activity at 60 μg/ml was 53.21%, compared to the standard (56.5%), and the minimal activity at 20 μg/ml was 30.21%, compared to the standard (36.89%). The environmentally friendly synthesizedMo NPsfrom Solanum xanthocarpum exhibited antioxidant activity. Furthermore, the findings showthat Mo NPs mediated by Solanum xanthocarpum can inhibit antibiotic-resistant bacteria, especially methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, andEnterococcus faecalis. In order to understand furtherhow nanoparticles work against bacteria that are resistant to many drugs,additional research and clinical studies would be needed.

Identification of a novel DNA repair inhibitor using an insilico driven approach shows effective combinatorial activity with genotoxic agents against multidrug-resistant Escherichia coli.

Increasing antimicrobial drug resistance represents a global existential threat. Infection is a particular problem in immunocompromised individuals, such as patients undergoing cancer chemotherapy, due to the targeting of rapidly dividing cells by antineoplastic agents. We recently developed a strategy that targets bacterial nucleotide excision DNA repair (NER) to identify compounds that act as antimicrobial sensitizers specific for patients undergoing cancer chemotherapy. Building on this, we performed a virtual drug screening of a ~120,000 compound library against the key NER protein UvrA. From this, numerous target compounds were identified and of those a candidate compound, Bemcentinib (R428), showed a strong affinity toward UvrA. This NER protein possesses four ATPase sites in its dimeric state, and we found that Bemcentinib could inhibit UvrA's ATPase activity by ~90% and also impair its ability to bind DNA. As a result, Bemcentinib strongly diminishes NER's ability to repair DNA in vitro. To provide a measure of in vivo activity we discovered that the growth of Escherichia coli MG1655 was significantly inhibited when Bemcentinib was combined with the DNA damaging agent 4-NQO, which is analogous to UV. Using the clinically relevant DNA-damaging antineoplastic cisplatin in combination with Bemcentinib against the urological sepsis-causing E. coli strain EC958 caused complete growth inhibition. This study offers a novel approach for the potential development of new compounds for use as adjuvants in antineoplastic therapy.

Unravelling the dilemma of self-medication in Egypt: a cross-sectional survey on knowledge, attitude, and practice of the general Egyptian population

BackgroundSelf-medication (SM) is a rising public health issue, especially in developing countries. It can be associated with various problems such as the delayed seeking of medical advice, drug interactions, and serious events such as antimicrobial drug resistance. We aimed to evaluate the Egyptian general population’s knowledge, attitudes, and practices of SM.MethodsWe employed a cross-sectional design between February 7th and March 8th, 2023 using a self-administered questionnaire available in Arabic. The questionnaire was developed based on previous studies and included four domains: sociodemographic data, knowledge, attitude, and practice of SM. We utilized both online (Google Forms) and paper surveys, utilizing convenience and snowball sampling methods. Data were analyzed using R Statistical Software (v4.1.3; R Core Team 2022).Results1630 Egyptian individuals (838 females and 792 males) from the seven provinces were enrolled, with a median age of 25 years (IQR: 22–40). Around 55.97% and 48.28% of the participants had good knowledge and favorable attitudes regarding SM respectively, while 62.8% had practiced SM in the previous three months. The most frequently used medications were painkillers (60.74%) followed by antibiotics (32.13%) and antipyretics (28.61%). The pharmacist’s recommendation was the source of SM for 53.61% while 31.53% used old medications at home. Most participants (59.08%) practiced SM because they thought they had simple or minor symptoms. The multivariate regression analysis revealed that females had significantly higher knowledge of SM than males (aOR: 2.10; 95%CI: 1.64—2.71; p-value < 0.001), with no significant differences in practice (aOR: 1.24; 95%CI: 0.99 – 1.56; p-value = 0.065). Individuals working or studying in the medical field were significantly more knowledgeable about SM (aOR: 4.30; 95%CI: 3.27–5.69; p-value < 0.001) and more likely to practice SM (aOR: 1.65; 95%CI: 1.26–2.17; p-value < 0.001). The odds of SM decreased with favorable attitudes (aOR: 0.44; 95%CI: 0.36–0.55; p-value < 0.001) while surprisingly, knowledge level was not significantly contributing to SM practice (aOR: 1.15; 95%CI: 0.90–1.48; p-value = 0.268).ConclusionsSM is prevalent in Egypt, highlighting the importance of raising awareness and encouraging physician consultation as a priority. Governments, healthcare organizations, and educational institutions need to collaborate to provide the necessary support and resources.

Capacity building to address antimicrobial resistance in remote Australia: The inaugural HOT NORTH Antimicrobial Academy

BackgroundRates of antimicrobial resistance (AMR) for some pathogens in Australia are considerably higher in rural and remote compared to urban regions. The inaugural Hot North Antimicrobial Academy was a 9-month educational programme aimed to build workforce knowledge and capacity in antimicrobial use, audit, stewardship, surveillance and drug resistance in remote primary health care. MethodsThe Academy was advertised to Aboriginal and Torres Strait Islander, regional and remote healthcare workers. Participants were Aboriginal health practitioners, nurses, pharmacists and doctors from Queensland, Northern Territory, South Australia and Western Australia working in remote primary health care with a focus on Indigenous health. Due to COVID-19 restrictions, the Academy ran virtually from February–November 2021 using Microsoft Teams. The Academy was evaluated using surveys and yarning circles to assess impact and knowledge gain. ResultsParticipants and faculty from across Australia attended 19 lectures and mentorship sessions. Eleven participants commenced and eight (73%) completed the Academy. The Academy raised participants awareness of AMR guidelines, governance and generating change; built confidence in advocacy; grew knowledge about drug resistant infections; and created a community of AMR champions in Indigenous health. ConclusionThe evaluation confirmed the Academy met the needs of participants, provided opportunities to move stewardship from tertiary hospitals into Indigenous and remote clinics and developed skills in research, audit, stewardship and advocacy for all involved. All sessions were recorded for future use, with facilitation by the National Aboriginal Community Controlled Health Organisation (NACCHO) in future years.

Antimicrobial Resistance: Techniques to Fight AMR in Bacteria – A Review

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.

Revisiting the smart metallic nanomaterials: advances in nanotechnology-based antimicrobials.

Despite significant advancements in diagnostics and treatments over the years, the problem of antimicrobial drug resistance remains a pressing issue in public health. The reduced effectiveness of existing antimicrobial drugs has prompted efforts to seek alternative treatments for microbial pathogens or develop new drug candidates. Interestingly, nanomaterials are currently gaining global attention as a possible next-generation antibiotics. Nanotechnology holds significant importance, particularly when addressing infections caused by multi-drug-resistant organisms. Alternatively, these biomaterials can also be combined with antibiotics and other potent biomaterials, providing excellent synergistic effects. Over the past two decades, nanoparticles have gained significant attention among research communities. Despite the complexity of some of their synthesis strategies and chemistry, unrelenting efforts have been recorded in synthesizing potent and highly effective nanomaterials using different approaches. With the ongoing advancements in nanotechnology, integrating it into medical procedures presents novel approaches for improving the standard of patient healthcare. Although the field of nanotechnology offers promises, much remains to be learned to overcome the several inherent issues limiting their full translation to clinics. Here, we comprehensively discussed nanotechnology-based materials, focusing exclusively on metallic nanomaterials and highlighting the advances in their synthesis, chemistry, and mechanisms of action against bacterial pathogens. Importantly, we delve into the current challenges and prospects associated with the technology.

A clade of Streptococcus pneumoniae clonal complex 320 with increased tolerance to β-lactam antibiotics in a Chinese metropolitan city

ObjectivesWe characterized the population structure and features of clinical Streptococcus pneumoniae isolates associated with invasive pneumococcal disease (IPD) from 2009 to 2017 in a Chinese metropolitan city using a whole-genome sequencing approach. MethodsSeventy-nine pneumococcal strains, including 60 serogroup-19 strains from children enduring IPD from a paediatric hospital in Shenzhen, were subjected to whole-genome sequencing. Population structure was characterized through phylogenetic analysis, sequence typing, serotyping, virulence factor, and antimicrobial drug resistance (AMR) gene profiling, combining the publicly available related WGS data. Clinical demography and antibiotic susceptibility profiles were compared among different populations to emphasize the higher-risk populations. Genetic regions associated with AMR gene mobilization were identified through comparative genomics. ResultsThese IPD strains mainly belonged to clonal complex 320 (CC320) and were composed of serotypes 19A and 19F. In addition to sporadic possible importation-related isolates (ST320), we identified an independent clade, CC320_SZpop (ST271), that predominantly circulated in Shenzhen and possibly expanded its range. Clinical features and antibiotic susceptibility analysis revealed that CC320_SZpop might manifest much higher pathogenicity and tolerance to β-lactams. Specific virulence factors in Shenzhen isolates of CC320_SZpop were identified. Furthermore, an ca. 40 kb hotspot genomic region enduring frequent recombination was identified, possibly associated with the divergence of S. pneumoniae strains. ConclusionA novel pneumococcal clade, CC320_SZpop, circulating in Shenzhen and other regions in China, possibly under expansion, was found and deserves more study and surveillance. Our study also emphasizes the importance of continuous genomic surveillance of clinical S. pneumoniae isolates, especially IPD isolates.

Invasive Streptococcus suis isolated in Spain contain a highly promiscuous and dynamic resistome.

Streptococcus suis is a major pathogen for swine and human. Here we aimed to know the rates of antimicrobial resistance (AMR) in invasive S. suis isolates recovered along Spain between 2016 - 2021 and elucidate their genetic origin. Antibiotic susceptibility testing was performed for 116 isolates of different genetic backgrounds and geographic origins against 18 antibiotics of 9 families. The association between AMR and genotypes and the origin of the isolates were statistically analyzed using Pearson´s chi-square test and the likelihood ratio. The antimicrobial resistant genes were identified by whole genome sequencing analysis and PCR screenings. High AMR rates (>80%) were detected for tetracyclines, spectinomycin, lincosamides, and marbofloxacin, medium (20-40%) for sulphonamides/trimethoprim, tiamulin, penicillin G, and enrofloxacin, and low (< 20%) for florfenicol, and four additional β-lactams. The occurrence of multidrug resistance was observed in 90% of isolates. For certain antibiotics (penicillin G, enrofloxacin, marbofloxacin, tilmicosin, and erythromycin), AMR was significantly associated with particular sequence types (STs), geographic regions, age of pigs, and time course. Whole genome sequencing comparisons and PCR screenings identified 23 AMR genes, of which 19 were previously reported in S. suis (aph(3')-IIIa, sat4, aadE, spw, aac(6')-Ie-aph(2'')-Ia, fexA, optrA, erm(B), mef(A/E), mrs(D), mph(C), lnu(B), lsa(E), vga(F), tet(M), tet(O), tet(O/W/32/O), tet(W)), and 4 were novel (aph(2'')-IIIa, apmA, erm(47), tet(T)). These AMR genes explained the AMR to spectinomycin, macrolides, lincosamides, tiamulin, and tetracyclines. Several genes were located on mobile genetic elements which showed a variable organization and composition. As AMR gene homologs were identified in many human and animal pathogens, the resistome of S. suis has a different phylogenetic origin. Moreover, AMR to penicillin G, fluoroquinolones, and trimethoprim related to mutations in genes coding for target enzymes (pbp1a, pbp2b, pbp2x, mraY, gyrA, parC, and dhfr). Bioinformatic analysis estimated traits of recombination on target genes, also indicative of gene transfer events. Our work evidences that S. suis is a major contributor to AMR dissemination across veterinary and human pathogens. Therefore, control of AMR in S. suis should be considered from a One Health approach in regions with high pig production to properly tackle the issue of antimicrobial drug resistance.

Prevalence and antimicrobial drug resistance of methicillin-resistant Staphylococcus aureus isolated from nasal swabs and milk samples of sheep and goats

Prevalence and antimicrobial drug resistance of methicillin-resistant Staphylococcus aureus isolated from nasal swabs and milk samples of sheep and goats

Antimicrobial drug resistance profiling of Pseudomonas aeruginosa isolated from nosocomial infections

Antimicrobial drug resistance profiling of Pseudomonas aeruginosa isolated from nosocomial infections

The impact of the BIOFIRE® Blood Culture Identification 2 Panel on antimicrobial treatment of children with suspected systemic inflammatory response syndrome and sepsis.

This study aimed to assess the therapeutic effects of implementing the BioFire® Blood Culture Identification 2 (BCID2) Panel (bioMérieux, Marcy l'Etoile, France) in the clinical practice of children with sepsis.This retrospective cross-sectional study included children from 15days of age to 18years old with sepsis and of whom the BCID2 Panel was studied from the positive blood culture. If the antimicrobial treatment was changed according to the results of BCID2 Panel, it was recorded and re-grouped as targeted antimicrobial therapy, de-escalation of the antimicrobial treatment and shifting to another antimicrobial drug if any antimicrobial resistance was detected. Seven-days and thirty-days mortality rate was recorded.Thirty-two patients with 36 septic episodes with positive BCID2 Panel results were included. The median age was 10months 15days (ranging from 15days to 16.5years). The mean difference between having positive results by the BCID2 Panel and conventional culture methods was 82.2 ± 45.4h (ranging from 12.3 to 207h). Effect of the BCID2 Panel on the antimicrobial treatment was detected in 69.4% of the episodes (n = 25). Glycopeptides were ceased at 6 patients, piperacillin/tazobactam was ceased at 6 patients, and cefotaxime was ceased at one patient and de-escalation was achieved in 13 episodes which formed the 36.1% of the initial antimicrobial treatment. Conclusion: The BCID2 Panel had an important impact on the patients care and optimization according to the principles of antimicrobial stewardship. The BCID2 Panel may be one of the key items for rapid and accurate diagnosis in children with sepsis. Blood culture is still the mainstay for especially detection of antimicrobial drug resistance, while BCID2 tests had several advantages such as speed and diagnostic accuracy as good as blood culture. What is Known: • The BioFire®Blood Culture Identification 2 (BCID2) Panel (bioMérieux, Marcy l'Etoile, France) is a well-validated assay that allows for the simultaneous identification of 43 nucleic acid targets associated with bloodstream infections within about 1h. What is New: • BCID2 Panel had a direct impact on the patient's treatment decision at the 69.4% of the sepsis episodes. • The clinicians received the microbiological results 82.2h earlier with BCID2 panel compared to blood culture methods with antimicrobial resistanceandde-escalation of the antimicrobial drugs was achieved at 13 episodes which formed the 36.1% of the initial treatment.

Global trends in antimicrobial resistance on organic and conventional farms

The important hypothesis that organic livestock management reduces the prevalence of antimicrobial resistance is either fiercely supported or bitterly contested. Yet, empirical evidence supporting this view remains fragmentary, in part because relationships between antimicrobial use and drug resistance vary dramatically across contexts, hosts, pathogens, and country-specific regulations. Here, we synthesize global policies and definitions of ‘organic’ and ask if organic farming results in notable reductions in the prevalence of antimicrobial resistance when directly examined alongside conventional analogs. We synthesized the results of 72 studies, spanning 22 countries and five pathogens. Our results highlight substantial variations in country-specific policies on drug use and definitions of ‘organic’ that hinder broad-scale and generalizable patterns. Overall, conventional farms had slightly higher levels of antimicrobial resistance (28%) relative to organic counterparts (18%), although we found significant context-dependent variation in this pattern. Notably, environmental samples from organic and conventional farms often exhibited high levels of resistance to medically important drugs, underscoring the need for more stringent and consistent policies to control antimicrobial contaminants in the soil (particularly on organic farms, where the application of conventional manure could faciliate the spread antimicrobial resistance). Taken together, these results emphasize the challenges inherent in understanding links between drug use and drug resistance, the critical need for global standards governing organic policies, and greater investment in viable alternatives for managing disease in livestock.

Сравнительный биоинформатический анализ состава генов антимикробной устойчивости в геномах представителей рода Corynebacterium

Currently, multidrug resistance of bacterial infectious agents poses a serious threat to the global public health. The following Corynebacterium strains are of special importance for infections, including hospital-acquired ones: C. amycolatum, C. urealyticum, C. striatum, C. jeikeium, C. aurimucosum, C. genitalium that are resistant to the broad spectrum of antimicrobial drugs. The study was aimed to conduct bioinformatics analysis of the pool of antimicrobial resistance genes in the published genomes of some members of the genus Corynebacterium. The data on the whole genome nucleotide sequences of 22 Corynebacterium isolates readily available from NCBI GenBank were assessed. Bioinformatics analysis of the whole genome sequences conducted in order to search for antimicrobial resistance genes in the specified genomes was performed using the PATRIC online resource. It was found that the genomes provided comprised various combinations of 25 antimicrobial drug resistance genes. Amino acid substitutions in GyrA (positions 87, 88 and 91) were revealed in some Corynebacterium strains, through which quinolone/fluoroquinolone resistance could be realized.

Bioaerosols released from multistage biofilter for gaseous benzene removal: Escape behavior and pathogenicity

Biological deodorization systems are widely used to control odors and volatile organic compounds. However, the secondary contamination of bioaerosol emissions is a noteworthy issue in the operation of biofilters for off-gas purification. In this study, a multistage biofilter for benzene treatment was utilized to investigate the bioaerosol emissions under different flow rates and spray intervals. At the outlet of the biofilter, 99–7173 CFU/m3 of bioaerosols were detected, among which pathogens accounted for 8.93–98.73 %. Proteobacteria and Firmicutes dominated bioaerosols at the phylum level. The Mantel test based on the Bray-Curtis distance revealed strong influences of flow rate introduced to the biofilter and biomass colonized on the packing materials (PMs) on bioaerosol emissions. The non-metric multidimensional scaling results suggested a correlation between the bioaerosol community and bacteria on the PMs. Bacillus and Stenotrophomonas were the two main genera stripped from the biofilm on PMs to form the bioaerosols. SourceTracker analysis confirmed that microorganisms from the PMs near outlet contributed an average of 22.3 % to bioaerosols. Pathogenic bacteria carried by bioaerosols included Bacillus, Serratia, Stenotrophomonas, Achromobacter, Enterococcus, and Pseudomonas. Bioaerosols were predicted to cause human diseases, with antimicrobial drug resistance and bacterial infectious disease being the two main pathogenic pathways. Stenotrophomonas sp. LMG 19833, Pseudomonas sp., and Stenotrophomonas sp. were the keystone species in the bioaerosol co-occurrence network. Overall, results of present study promote the insight of bioaerosols, particularly pathogen emissions, and provide a basis for controlling bioaerosol contamination from biofilters.

Targeting FMN, TPP, SAM-I, and glmS Riboswitches with Chimeric Antisense Oligonucleotides for Completely Rational Antibacterial Drug Development.

Antimicrobial drug resistance has emerged as a significant challenge in contemporary medicine due to the proliferation of numerous bacterial strains resistant to all existing antibiotics. Meanwhile, riboswitches have emerged as promising targets for discovering antibacterial drugs. Riboswitches are regulatory elements in certain bacterial mRNAs that can bind to specific molecules and control gene expression via transcriptional termination, prevention of translation, or mRNA destabilization. By targeting riboswitches, we aim to develop innovative strategies to combat antibiotic-resistant bacteria and enhance the efficacy of antibacterial treatments. This convergence of challenges and opportunities underscores the ongoing quest to revolutionize medical approaches against evolving bacterial threats. For the first time, this innovative review describes the rational design and applications of chimeric antisense oligonucleotides as antibacterial agents targeting four riboswitches selected based on genome-wide bioinformatic analyses. The antisense oligonucleotides are coupled with the cell-penetrating oligopeptide pVEC, which penetrates Gram-positive and Gram-negative bacteria and specifically targets glmS, FMN, TPP, and SAM-I riboswitches in Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli. The average antibiotic dosage of antisense oligonucleotides that inhibits 80% of bacterial growth is around 700 nM (4.5 μg/mL). Antisense oligonucleotides do not exhibit toxicity in human cell lines at this concentration. The results demonstrate that these riboswitches are suitable targets for antibacterial drug development using antisense oligonucleotide technology. The approach is fully rational because selecting suitable riboswitch targets and designing ASOs that target them are based on predefined criteria. The approach can be used to develop narrow or broad-spectrum antibiotics against multidrug-resistant bacterial strains for a short time. The approach is easily adaptive to new resistance using targeting NGS technology.