Antibiotic Resistance Mechanisms Research Articles

N-Alkane Assimilation by Pseudomonas aeruginosa and Its Interactions with Virulence and Antibiotic Resistance

Pseudomonas aeruginosa strains with potential for degrading n-alkanes are frequently cultured from hydrocarbon-contaminated sites. The initial hydroxylation step of long-chain n-alkanes is mediated by the chromosomally encoded AlkB1 and AlkB2 alkane hydroxylases. The acquisition of an additional P. putida GPo1-like alkane hydroxylase gene cluster can extend the substrate range assimilated by P. aeruginosa to <C12 n-alkanes. Efficient niche colonization of hydrocarbon-contaminated sites is facilitated by avid iron-uptake systems, such as pyoverdine, and the production of several compounds with antimicrobial activities. A GPo1-like gene cluster can facilitate detoxification and solvent tolerance in P. aeruginosa. The overproduction of various multidrug efflux pumps, in particular, the MexAB-OprM system, can also contribute to solvent tolerance, which is often associated with reduced susceptibility or full resistance to certain clinically relevant antibiotics. These characteristics, together with the remarkable conservation of P. aeruginosa virulence determinants among human, animal, and environmental isolates, necessitate further studies from a One Health perspective into the acquired antibiotic resistance mechanisms of environmental P. aeruginosa strains and possible ways for their dissemination into the human population.

Klebsiella in Wildlife: Clonal Dynamics and Antibiotic Resistance Profiles, a Systematic Review

Klebsiella spp. are a genus of Gram-negative, opportunistic bacteria frequently found in the flora of the mucosal membranes of healthy animals and humans, and in the environment. Species of this group can cause serious infections (meningitis, sepsis, bacteraemia, urinary tract infections, liver damage) and possible death in immunocompromised organisms (and even in immunocompetent ones in the case of hypervirulent K. pneumoniae) that are exposed to them. K. pneumoniae is part of the ESKAPE organisms, and so it is important to understand this genus in terms of multidrug-resistant bacteria and as a carrier of antibiotic resistance mechanisms. As it is a durable bacterium, it survives well even in hostile environments, making it possible to colonize all kinds of habitats, even the mucosal flora of wildlife. This systematic review explores the prevalence of Klebsiella spp. bacteria in wild animals, and the possibility of transmission to humans according to the One Health perspective. The isolates found in this review proved to be resistant to betalactams (blaTEM, blaOXA-48…), aminoglycosides (strAB, aadA2…), fosfomycin, tetracyclines, sulphonamides, trimethoprim, phenicols (catB4), and polymyxins (mcr4).

Antibiotic resistant Pseudomonas aeruginosa in dental unit waterline: a case study in Milan (Italy)

Abstract P.aeruginosa (Pa) is one of the most serious cause of healthcare-associated bacteremia, well-known for its antibiotic resistance (AR). Pa has often been found in dental unit water representing a great risk in public health. Aims are to evaluate the presence of Pa in dental unit (DU) water and its phenotypic and genotypic properties. Pa isolates derive from a monitoring of DU water in an Italian hospital (Milan). Samples were collected on Monday and on Friday, before the beginning and after the end of activities. Resistant PA strains were characterized by phenotypic method using E-test for 6 different classes of antibiotics, and by genotypic method with Whole-genome sequencing (WGS). Resistance genes were annotated with ResFinder v. 4.5 and Sequence Type (ST) was determined using the PA MLST database. 70/272 strains were identified as Pa and 21 of them were AR to one or more antibiotics. They were detected in 10/44 (22.7%) DUs and 2/4 (50%) control sinks (1-2000UFC/100mL). WGS was obtained for 18 strains. 17 belonged to serogroup O11 and ST667 was prevalent (8/18) followed by ST395 (4/18). At the ground floor ST395 was the most prevalent, followed by ST667 and 260, while, at the first floor, ST309 and 667 were in the two controls and ST667, 3245 and 260 in the other DUs. Resistant genes blaPAO, aph(3’)-IIb, catB7 conferring resistance to β-lactams, aminoglycosides and amphenicol, respectively, were observed in all isolates. Only ST3245 strain did not show resistance to Fosfomycin. Genotypic and phenotypic analyses present some discrepancies with the presence of AR genes and no antibiotic resistance detection (4/18) or resistance to other different classes of antibiotics (6/18). The MLST analyses showed a high diversity, with the presence of strains sharing different antibiotic resistance mechanisms in DU water. Detection and analyses by WGS can help to track dissemination of genetic resistance determinants and potential emergence of high-risk clones. Key messages • Phenotypic and genotypic analyses in DU water are needed to evaluate risk for human health, in addition to routine microbial monitoring. • WGS can help to track dissemination of genetic resistance determinants and potential emergence of high-risk clones.

Stenotrophomonas maltophilia – A Threatening Nosocomial Pathogen

Abstract Stenotrophomonas maltophilia is a ubiquitous Gram-negative rod which has emerged as one of the major causes of nosocomial infections. It can cause pneumonia, septicemia, meningitis, urinary tract, and wound infections, and is associated with high mortality in immune-compromised patients. Pathogenesis in S. maltophilia infections is an outcome of multiple virulence factors, including outer membrane lipopolysaccharide, extracellular enzymes, porins, pilli, biofilm formation, motility, and small colony variants, among others. S. maltophilia shows high intrinsic and acquired resistance to all commonly used antibiotics, limiting the number of therapeutic choices. The aim of this review is to summarize the virulence factors, antibiotic resistance mechanisms, diagnosis, and treatment of S. maltophilia infections.

Genomic insight on Klebsiella variicola isolated from wastewater treatment plant has uncovered a novel bacteriophage

Klebsiella variicola is considered an emerging pathogen, which may colonize a variety of hosts, including environmental sources. Klebsiella variicola investigated in this study was obtained from an influent wastewater treatment plant in the North-West Province, South Africa. Whole genome sequencing was conducted to unravel the genetic diversity and antibiotic resistance patterns of K. variicola. Whole genome core SNP phylogeny was employed on publicly available 170 genomes. Furthermore, capsule types and antibiotic resistance genes, particularly beta-lactamase and carbapenems genes were investigated from the compared genomes. A 38 099 bp bacteriophage was uncovered alongside with K. variicola genome. Whole genome sequencing revealed that the extended beta-lactamase blaLEN (75.3%) of the beta-lactamase is dominant among compared K. variicola strains. The identified IncF plasmid AA035 confers resistance genes of metal and heat element subtypes, i.e., silver, copper, and tellurium. The capsule type KL107-D1 is a predominant capsule type present in 88.2% of the compared K. variicola genomes. The phage was determined to be integrase-deficient consisting of a fosB gene associated with fosfomycin resistance and clusters with the Wbeta genus Bacillus phage group. In silico analysis showed that the phage genome interacts with B. cereus as opposed to K. variicola strain T2. The phage has anti-repressor proteins involved in the lysis-lysogeny decision. This phage will enhance our understanding of its impact on bacterial dissemination and how it may affect disease development and antibiotic resistance mechanisms in wastewater treatment plants. This study highlights the need for ongoing genomic epidemiological surveillance of environmental K. variicola isolates.

Effects and Mechanisms of Lactobacillus Probiotics in Maintaining Women’s Vaginal Health: A Review

Probiotics are beneficial living microorganisms. They are useful to vaginal health when consumed in suitable doses. The dominant species included in probiotics are Lactobacillus. We can get these microbes naturally or commercially utilize them as functional food. Lactobacillus species form 70% of inhabitant bacteria in females compared to other warm-blooded animals. The prevalent Lactobacillus species are L. crispatus, L. gasseri, L. iners and L. jensenii. Because of the development of antibiotic resistance mechanisms, the beneficial relationship between humans and probiotics has been discussed for several years. Lactobacillus prevents the attachment of pathogens by using several mechanisms, for example, by increasing estrogen levels, production of lactic acid, lowering pH 4.0-4.5 to provide an acidic environment, release of hydrogen peroxide, bacteriocins and bacteriocins-like substances, adhesion and colonization properties. Lactobacillus prevent the entry and attachment of pathogenic bacteria, thus not only helping to control and manage different gynecological conditions like bacterial vaginosis, endometriosis, vulvovaginal candidiasis and genitourinary syndrome of menopause but also infections that can spread through sexual contacts such as gonorrhea, chlamydia, genital herpes, Human papillomavirus infections (HPV). Overall, the use of probiotics in improving vaginal health is beneficial, easy and cost-effective but the use of probiotics in HPV clearance is not quite beneficial. So, more work should be done on HPV preventive vaccines.

A Descriptive Study on the Phenotypic Variability of Pseudomonas aeruginosa Identified by MALDI-TOF

This descriptive study investigates the phenotypic variability of 50 Pseudomonas aeruginosa colonies isolated from wastewater, identified using MALDI-TOF mass spectrometry. The contamination of wastewater by opportunistic pathogens like P. aeruginosa poses significant public health risks due to their potential to cause severe infections and contribute to the spread of antimicrobial resistance. Pseudomonas aeruginosa is particularly concerning because of its remarkable adaptability, resilience, and intrinsic and acquired antibiotic resistance mechanisms, including the production of beta-lactamases, efflux pumps, and target site mutations. Our study highlights the phenotypic diversity and antibiotic resistance profiles of P. aeruginosa strains isolated from urban and hospital environments. Using MALDI-TOF MS, we rapidly and accurately characterized these strains, providing species-level identification within minutes. This technology surpasses traditional biochemical methods in speed and accuracy, revolutionizing microbial diagnostics by offering a high-throughput, cost-effective, and reliable tool. By analyzing the phenotypic traits and resistance mechanisms of these strains, we aim to provide critical insights into their ecology and inform strategies to mitigate the risks associated with their presence in the environment. The antibiotic resistance profiles revealed varied susceptibility among the strains, with notable resistance to drugs such as erythromycin, cefoxitin, and tetracycline. The study's findings underscore the importance of integrating advanced diagnostic technologies like MALDI-TOF MS into routine environmental monitoring and public health strategies to address the challenges posed by P. aeruginosa in wastewater. Ultimately, this research contributes to understanding the dynamics of contamination and resistance in urban environments. By detailing the methodology used for the identification and characterization of the strains, as well as the results obtained, this publication aims to provide a valuable database for researchers and practitioners engaged in combating nosocomial infections and environmental pollution by P. aeruginosa. This study highlights the need for effective management measures to control the dissemination of this pathogen in aquatic systems, promoting public health and environmental safety.

New therapeutic approaches for S.aureus infections treatment

Staphylococcus aureus (S. aureus) is an opportunistic pathogen that causes a range of diseases, from mild skin and soft tissue infections and food poisoning to serious conditions such as pneumonia, endocarditis, sepsis, and hospital-acquired infections. Due to the aggressive nature of the disease, limitations of existing treatments, and the spread of antibiotic-resistant strains, the development of alternative strategies to combat bacterial infections has progressed faster than the development of new antibiotics. In this review, we analyze the epidemiological situation of morbidity and mortality associated with S. aureus infection, as well as antimicrobial resistance of this organism on a global scale. We reviewed the pathogenesis and virulent factors of S. aureus, their mechanisms of antibiotic resistance, and the importance of diagnosing staphylococcal infections to ensure timely intervention. This review also discusses the latest approaches to combating antibiotic resistance in Staphylococcus aureus, including preventive and therapeutic antimicrobial strategies. Such methods as the use of bacteriophages in treatment, antimicrobial peptides, probiotic microorganisms and their metabolites, and the use of inhibitors to suppress bacterial communication are considered.

A novel PhoPQ-potentiated mechanism of colistin resistance impairs membrane integrity in Pseudomonas aeruginosa.

Polymicrobial communities are often recalcitrant to antibiotic treatment because interactions between different microbes can dramatically alter their responses and susceptibility to antimicrobials. However, the mechanisms of evolving antimicrobial resistance in such polymicrobial environments are poorly understood. We previously reported that Mg 2+ depletion caused by the fungus Candida albicans can enable Pseudomonas aeruginosa to acquire significant resistance to colistin, a last-resort antibiotic targeting bacterial membrane. Here, we dissect the genetic and biochemical basis of this increased colistin resistance. We show that P. aeruginosa cells can acquire colistin resistance using three distinct evolutionary trajectories involving mutations in genes involved in lipid A biosynthesis, lipid A modifications that are dependent on low Mg 2+ , and a putative Mg 2+ transporter, PA4824. These mutations confer colistin resistance by altering acyl chains, hydroxylation, and aminoarabinose modification of lipid A moieties on the bacterial outer membrane. In all cases, enhanced colistin resistance initially depends on the low Mg 2+ -responsive PhoPQ pathway, which potentiates the evolution of resistance mutations and lipid A modifications that do not occur without Mg 2+ depletion. However, the PhoPQ pathway is not required to maintain high colistin resistance in all cases. In most cases, the genetic and biochemical changes associated with these novel forms of colistin resistance also impair bacterial membrane integrity, leading to fitness costs. Our findings provide molecular insights into how nutritional competition drives a novel antibiotic resistance mechanism and its ensuing fitness tradeoffs.

Etiology of nosocomial infections and antibiotic resistance (level of antibiotic resistance) of identified pathogens in patients with traumatic chest injuries

Background. Chest injuries and wounds are common during armed conflicts, with frequent nosocomial infections and mortality up to 35-45% [1-4]. Infectious complications associated with multidrug-resistant microorganisms are an urgent issue in the management of patients with trauma. Aim. To conduct a retrospective review of the main causative agents of infectious complications in patients with traumatic chest injuries and evaluate antibiotic resistance of isolated pathogens. Materials and methods. Samples for microbiological examination were obtained from 160 patients with chest trauma and nosocomial complications. The samples included sputum, pleural fluid, bronchial washings obtained by fiberoptic bronchoscopy, and tracheal secretions. Antibacterial susceptibility tests were performed, and the antibiotic resistance mechanisms in isolated microorganisms were determined. Results. Gram-negative pathogens accounted for 93% of cases. The following organisms prevailed: Klebsiella pneumoniae – 42%, Acinetobacter baumannii – 28%, Pseudomonas aeruginosa – 18%, Escherichia coli – 9%. Of note, 91.4% of K. pneumoniae strains produced extended-spectrum β-lactamases and carbapenemases. The percentage of multidrug-resistant and pandrug-resistant strains was 48.2% and 52%, respectively. Conclusion. The data obtained indicate a wide spread of gram-negative microorganisms and their multiple resistance in patients with traumatic breast injuries complicated by nosocomial infection.

Breaking Barriers: Exploiting Envelope Biogenesis and Stress Responses to Develop Novel Antimicrobial Strategies in Gram-Negative Bacteria.

Antimicrobial resistance (AMR) has emerged as a global health threat, necessitating immediate actions to develop novel antimicrobial strategies and enforce strong stewardship of existing antibiotics to manage the emergence of drug-resistant strains. This issue is particularly concerning when it comes to Gram-negative bacteria, which possess an almost impenetrable outer membrane (OM) that acts as a formidable barrier to existing antimicrobial compounds. This OM is an asymmetric structure, composed of various components that confer stability, fluidity, and integrity to the bacterial cell. The maintenance and restoration of membrane integrity are regulated by envelope stress response systems (ESRs), which monitor its assembly and detect damages caused by external insults. Bacterial communities encounter a wide range of environmental niches to which they must respond and adapt for survival, sustenance, and virulence. ESRs play crucial roles in coordinating the expression of virulence factors, adaptive physiological behaviors, and antibiotic resistance determinants. Given their role in regulating bacterial cell physiology and maintaining membrane homeostasis, ESRs present promising targets for drug development. Considering numerous studies highlighting the involvement of ESRs in virulence, antibiotic resistance, and alternative resistance mechanisms in pathogens, this review aims to present these systems as potential drug targets, thereby encouraging further research in this direction.

Determinants of Antibiotic Resistance and Virulence Factors in the Genome of Escherichia coli APEC 36 Strain Isolated from a Broiler Chicken with Generalized Colibacillosis.

Objective: Multidrug-resistant, highly pathogenic Escherichia coli strains are the primary causative agents of intestinal and extraintestinal human diseases. The extensive utilization of antibiotics for farm animals has been identified as a contributing factor to the emergence and dissemination of E. coli strains that exhibit multidrug resistance and possess high pathogenic potential. Consequently, a significant research objective is to examine the genetic diversity of pathogenic E. coli strains and to identify those that may pose a threat to human health. Methods: In this study, we present the results of genome sequencing and analysis, as well as the physiological characterization of E. coli strain APEC 36, which was isolated from the liver of a broiler chicken with generalized colibacillosis. Results: We found that APEC 36 possess a number of mechanisms of antibiotic resistance, including antibiotic efflux, antibiotic inactivation, and antibiotic target alteration/replacement/protection. The most widely represented group among these mechanisms was that of antibiotic efflux. This finding is consistent with the strain's documented resistance to multiple antibiotics. APEC 36 has an extremely rare variant of the beta-lactamase CTX-M-169. Notwithstanding the multitude of systems for interfering with foreign DNA present in the strain, seven plasmids have been identified, three of which may possess novel replication origins. Additionally, qnrS1, which confers resistance to fluoroquinolones, was found to be encoded in the genome rather than in the plasmid. This suggests that the determinants of antibiotic resistance may be captured in the genome and stably transmitted from generation to generation. Conclusions: The APEC 36 strain has genes for toxins, adhesins, protectins, and an iron uptake system. The obtained set of genetic and physiological characteristics allowed us to assume that this strain has a high pathogenic potential for humans.

Revealing antibiotic resistance's ancient roots: insights from pristine ecosystems.

The prevailing belief that antibiotic resistance mechanisms emerged with human antibiotic use has been challenged. Evidence indicates that some antibiotic resistance genes (ARGs) have a long evolutionary history, predating the advent of antibiotics in human medicine, thereby demonstrating that resistance is an ancient phenomenon. Despite extensive surveys of resistance elements in environments impacted by human activity, limited data are available from remote and pristine habitats. This minireview aims to compile the most relevant research on the origins and evolution of ARGs in these habitats, which function as reservoirs for ancient resistance mechanisms. These studies indicate that ancient ARGs functionally similar to modern resistance genes, highlighting the general role of natural antimicrobial substances in fostering the evolution and exchange of diverse resistance mechanisms through horizontal gene transfer over time. This minireview underscores that antibiotic resistance was present in ancestral microbial communities and emphasizes the ecological role of antibiotics and resistance determinants. Understanding ancient ARGs is crucial for predicting and managing the evolution of antibiotic resistance. Thus, these insights provide a foundational basis for developing new antibiotics and strategies for microbial resistance management.

Isolation and molecular characterization of multi-drug resistant uropathogenic Escherichia coli from urine samples: Insights into urinary tract infection management

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) present a significant global health burden. With UPEC responsible for approximately 90 % of UTIs, understanding its mechanisms of virulence and antibiotic resistance is paramount for effective treatment strategies. This study aimed to investigate the prevalence of multi-drug resistant (MDR) E. coli strains in urinary tract infections and to elucidate the molecular mechanisms underlying their resistance. A total of 150 E. coli isolates were obtained from urinary tract infection specimens collected patients at Doctor’s Diagnostic Centre in Kalyan Nagar, Bangalore over four months November 2022 to February 2023. Isolation and screening of pathogenic E. coli were conducted using Eosin Methylene Blue Agar and Nutrient Agar, followed by identification through gram staining and biochemical characterization tests. Antibiotic susceptibility testing was performed using Mueller-Hinton agar and various antibiotic discs. Phenotypic and molecular identification of extended-spectrum beta-lactamase (ESBL) producers were conducted, along with the screening for specific antibiotic resistance genes using polymerase chain reaction (PCR). Of the 150 E. coli isolates, 57.3 % were found to be multi-drug resistant, with all 35 isolates from hospitalized patients exhibiting MDR characteristics. Phenotypic and molecular analyses revealed the presence of ESBL-producing isolates, with the blaCTX-M, blaTEM, and blaSHV genes detected in PCR assays. Plasmid extraction and PCR assays further identified the presence of plasmid-encoded carbapenemase genes (blaOXA-48, blaNDM-1, blaKPC-2), as well as other antibiotic resistance genes including those conferring resistance to fluoroquinolones. The results underscore the alarming prevalence of MDR E. coli strains in urinary tract infections, particularly in hospitalized patients. Molecular characterization revealed the diverse genetic mechanisms contributing to antibiotic resistance, including the presence of ESBLs and plasmid-encoded resistance genes. These findings emphasize the urgent need for surveillance and infection control measures to mitigate the spread of MDR pathogens and the development of alternative therapeutic strategies to combat antibiotic resistance in UTIs.

Mechanisms of the Quorum Sensing Systems of Pseudomonas aeruginosa: Host and Bacteria.

Quorum-sensing is a communication mechanism between bacteria with the ability to activate signaling pathways in the bacterium and in the host cells. Pseudomonas aeruginosa is a pathogen with high clinical relevance due to its vast virulence factors repertory and wide antibiotic resistance mechanisms. Due to this, it has become a pathogen of interest for developing new antimicrobial agents in recent years. P. aeruginosa has three major QS systems that regulate a wide gene range linked with virulence factors, metabolic regulation, and environment adaption. Consequently, inhibiting this communication mechanism would be a strategy to prevent the pathologic progression of the infections caused by this bacterium. In this review, we aim to overview the current studies about the signaling mechanisms of the QS system of P. aeruginosa and its effects on this bacterium and the host.

Synergistic Effects of Probiotics and Ciprofloxacin on Gene Expression in Klebsiella Pneumoniae Isolated from Urine and Sputum Specimens

Background: Antibiotic resistance is associated with efflux pumps and resistance genes, among the significant threats to health systems worldwide. The efflux pumps and resistance genes that distinguish many antibiotics are called Multidrug Resistance (MDR), and probiotics are essential treatments for some bacterial inflammation caused by K. pneumonia. Our research, which takes a unique approach by investigating the prevalence of Klebsiella pneumoniae bacteria that cause different clinical infections, has the potential to impact the field of antibiotic resistance studies significantly. By identifying the (AcrA and gyrA) genes using the polymerase chain reaction and exploring the synergistic effect of probiotics and Ciprofloxacin antibiotics on some virulence genes in K. pneumoniae, we aim to contribute to the understanding of antibiotic resistance mechanisms and potential new treatment strategies. Our methods were meticulously designed and executed, underscoring the reliability of our results. From December 2022 to June 2023, we collected 199 samples from patients with urinary tract infections (UTIs) and sputum at Baquba Teaching Hospital and Al-Batoul Maternity Hospital in Diyala Governorate, Iraq. The nucleic acid DNA of the bacterial isolates under study was carefully extracted, and then the polymerase chain reaction (PCR) was performed using specialized gene primers (AcrA and gyrA). The RNA of the bacterial isolates was extracted, and then quantitative real-time (q-Rt PCR) was performed to detect gene expression by the AcrA and gyrA genes. Results: The results of antibiotic sensitivity showed that all isolates were 100% resistant to Ampicillin, 87.71% Cefoxitin, 64.91% Trimethoprim-sulfamethoxazole, 50.87% Amikacin, 35.08% Levofloxacin, 26.31% Imipenem, and 22.80% Ciprofloxacin. The study results showed that all bacterial isolates (22) obtained the genes (AcrA and gyrA) in percentage 100%. The current study showed an inhibition in the gene expression of the AcrA and gyrA genes; there was an inhibition in gene expression for the two isolates (U4, S2) after treatment with probiotics and a synergistic of probiotics and ciprofloxacin and compared to Control. Conclusion: Most Klebsiella pneumoniae isolates under study were isolated from patients with (UTIs) and sputum with multiple antibiotic resistance (MDR). All bacterial isolates possessed the genes (AcrA and gyrA) in a percentage of (100%), and there was inhibition in the gene expression of the AcrA and gyrA genes after treatment with probiotics and a synergistic of probiotics and ciprofloxacin.

Gene Expression Of Some Antibiotic Resistance Mechanisms In Neisseria Gonorrhoeae Isolated From Iraqi Patients

Background: Treatment of N. gonorrhoeae infection is restricted by the rising commonness of multidrug-resistance strains. The point of this study was to evaluate antibiotic resistance and mRNA expression of penA, pilQ, norM, farA, and mtrE of N. gonorrhea. Method: one hindered samples collected from patients infected with N. gonorrhoeae. The bacteria were isolated and diagnosed using culture media and biochemical tests. Using the MIC method, the sensitivity of bacteria to penicillin, ciprofloxacin, ceftriaxone, spectinomycin, tetracycline, and azithromycin was determined. After RNA extraction and cDNA production, gene expression of penA, pilQ, norM, farA, and mtrE was assessed using real time -qPCR. Results: we found all isolates sensitive to ceftriaxone and azithromycin. Clear increase in penA, pilQ, farA, and mtrE gene expression of penicillin-resistant isolates (1.571, 3.135, 0.010 and 34.24 respectively), while norM gene expression decreased in those isolates. High gene expression for pilQ, farA, and mtrE among isolates resistant to ciprofloxacin (0.0041, 0.00072, 0.011 respectively). Tetracycline-resistant isolates appeared to have higher gene expression for penA, norM, farA, and mtrE (0.0033, 8.669, 37.85, 15.84 respectively). Spectinomycin-resistant isolates have high gene expression for penA, pilQ, norM, farA, and mtrE (0.222, 0.021, 0.036, 0.0002, 19.63 respectively) . Moreover, gene expression of penA, norM, and farA increased in males (6.938, 1.095, 7.946 respectively) while the rate of gene expression for pilQ and mtrE increased in females (0.161 and 7.832 respectively). Conclusion: gene expression of penA, pilQ, norM, farA, and mtrE increased in most antibiotics resistance isolates especially of bacterial infection that isolated from males.

Antimicrobial Resistance in Diverse Escherichia coli Pathotypes from Nigeria.

Escherichia coli is a gram-negative commensal bacterium living in human and animal intestines. Its pathogenic strains lead to high morbidity and mortality, which can adversely affect people by causing urinary tract infections, food poisoning, septic shock, or meningitis. Humans can contract E. coli by eating contaminated food-such as raw or undercooked raw milk, meat products, and fresh produce sold in open markets-as well as by coming into contact with contaminated settings like wastewater, municipal water, soil, and faeces. Some pathogenic strains identified in Nigeria, include Enterohemorrhagic (Verotoxigenic), Enterotoxigenic, Enteropathogenic, Enteroinvasive, and Enteroaggregative E. coli. This causes acute watery or bloody diarrhoea, stomach cramps, and vomiting. Apart from the virulence profile of E. coli, antibiotic resistance mechanisms such as the presence of blaCTX-M found in humans, animals, and environmental isolates are of great importance and require surveillance and monitoring for emerging threats in resource-limited countries. This review is aimed at understanding the underlying mechanisms of evolution and antibiotic resistance in E. coli in Nigeria and highlights the use of improving One Health approaches to combat the problem of emerging infectious diseases.

Machine Learning and Deep Learning Models for Predicting Noncovalent Inhibitors of AmpC β-Lactamase.

Continuous use of antibiotics leads to the ability of bacteria to adapt by developing complex antibiotic resistance (AR) mechanisms. The synthesis of β-lactamases is a widely observed AR mechanism. The class C β-lactamase (AmpC) causes significant resistance toward β-lactam antibiotics, and new treatments are urgently needed. Noncovalent inhibitors have been developed against a broad spectrum of β-lactamases. In this study, we developed robust and accurate models for predicting noncovalent inhibitors of AmpC using large compound data sets and machine/deep learning modeling. We created support vector machine (SVM), random forest (RF), and feed-forward neural network (FFNN) classification models. The cross-validation (CV) accuracies varied between 80 and 82%, as combined models reached an accuracy of 83%. We analyzed the physicochemical characteristics of the noncovalent inhibitors and predicted the binding modes for some of them. Such models are helpful for identifying new noncovalent inhibitors in order to establish novel solutions against the growing resistance to standard β-lactam inhibitors. The best RF, SVM, and FFNN models for predicting noncovalent inhibitors of AmpC β-lactamase are available in the GitHub repository, https://github.com/UPCmctr/ML-DL-AmpC-B-lactamase.

Evaluation of the Antibacterial Potential of Two Short Linear Peptides YI12 and FK13 against Multidrug-Resistant Bacteria.

The accelerating spread of antibiotic resistance has significantly weakened the clinical efficacy of existing antibiotics, posing a severe threat to public health. There is an urgent need to develop novel antimicrobial alternatives that can bypass the mechanisms of antibiotic resistance and effectively kill multidrug-resistant (MDR) pathogens. Antimicrobial peptides (AMPs) are one of the most promising candidates to treat MDR pathogenic infections since they display broad-spectrum antimicrobial activities and are less prone to achieve drug resistance. In this study, we investigated the antibacterial capability and mechanisms of two machine learning-driven linear peptide compounds termed YI12 and FK13. We reveal that YI12 and FK13 exhibit broad-spectrum antibacterial properties against clinically significant bacterial pathogens, inducing no or minimal hemolysis in mammalian red blood cells. We further ascertain that YI12 and FK13 are resilient to heat and acid-base conditions, and exhibit susceptibility to hydrolytic enzymes and divalent cations under physiological conditions. Initial mechanistic investigations reveal that YI12 and FK13 compromise bacterial membrane integrity, leading to membrane potential dissipation and excessive reactive oxygen species (ROS) generation. Collectively, our findings highlight the prospective utility of these two cationic amphiphilic peptides as broad-spectrum antibacterial agents.