Molecular mechanisms of tigecycline-resistance among Enterobacterales. - Related Documents




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488001.0000Molecular mechanisms of tigecycline-resistance among Enterobacterales. The global emergence of antimicrobial resistance to multiple antibiotics has recently become a significant concern. Gram-negative bacteria, known for their ability to acquire mobile genetic elements such as plasmids, represent one of the most hazardous microorganisms. This phenomenon poses a serious threat to public health. Notably, the significance of tigecycline, a member of the antibiotic group glycylcyclines and derivative of tetracyclines has increased. Tigecycline is one of the last-resort antimicrobial drugs used to treat complicated infections caused by multidrug-resistant (MDR) bacteria, extensively drug-resistant (XDR) bacteria or even pan-drug-resistant (PDR) bacteria. The primary mechanisms of tigecycline resistance include efflux pumps' overexpression, tet genes and outer membrane porins. Efflux pumps are crucial in conferring multi-drug resistance by expelling antibiotics (such as tigecycline by direct expelling) and decreasing their concentration to sub-toxic levels. This review discusses the problem of tigecycline resistance, and provides important information for understanding the existing molecular mechanisms of tigecycline resistance in Enterobacterales. The emergence and spread of pathogens resistant to last-resort therapeutic options stands as a major global healthcare concern, especially when microorganisms are already resistant to carbapenems and/or colistin.202438655285
488110.9999Investigating colistin drug resistance: The role of high-throughput sequencing and bioinformatics. Bacterial infections involving antibiotic-resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR), extensive-drug resistant (XDR) or pan-drug resistant (PDR) bacterial strains. Most recently, plasmid-mediated resistance to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR, XDR and PDR gram-negative bacteria has been reported. Plasmid-mediated colistin resistant gram-negative bacteria have been described to be PDR, implying a state devoid of alternative antibiotic therapeutic options. This review concisely describes the evolution of antibiotic resistance to plasmid-mediated colistin resistance and discusses the potential role of high-throughput sequencing technologies, genomics, and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antibiotic resistance as a whole.201931354944
488420.9999Multidrug resistance efflux pump expression in uropathogenic Gram-negative bacteria in organ transplant recipients. Urinary tract infections (UTIs) are common in healthcare settings and communities; and are predominantly caused by Gram-negative bacteria, which account for > 70% of UTI cases. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are the most common bacterial agents responsible for UTIs. The emergence of antibiotic resistance poses a challenge for UTI treatment; and efflux pump overexpression contributes to Gram-negative bacterial resistance. This comprehensive review summarizes the current understanding of multidrug resistance (MDR) efflux pump expression in prevalent Gram-negative bacteria that demonstrate resistance to antibiotics predominantly used for UTI treatment. This review examines the available data, and offers insights into the role of efflux pumps in conferring MDR to UTI-causing bacteria. Understanding these resistance mechanisms is crucial for developing effective strategies to combat antibiotic resistance in UTI management. Furthermore, this review emphasizes the need to characterize efflux pump-mediated antimicrobial resistance in solid organ transplantation cases. Solid organ transplant recipients are particularly vulnerable to UTIs caused by MDR bacteria, posing a serious threat to their health and recovery. Identifying the efflux pump profiles of these bacterial strains can guide appropriate antibiotic choices and optimize treatment outcomes in transplant recipients. By consolidating existing knowledge on efflux pump expression in antibiotic-resistant Gram-negative bacteria associated with UTIs, this review acknowledges gaps and identifies the future scope of research that should address the growing challenge of MDR UTIs, particularly in high-risk populations such as solid organ transplant recipients.202540452526
487930.9999Prevalence of polymyxin resistance through the food chain, the global crisis. Antimicrobial resistance is one of the vital challenges facing global health today. Multi-drug resistant (MDR) infections are often treated with the narrow-spectrum drugs, colistin (polymyxin E) or polymyxin B, which are last-resort antibiotics for human therapeutics that are effective against Gram-negative bacteria. Unfortunately, resistance to these polymyxins has occurred because of selective pressure caused by the inappropriate use of those antibiotics, especially in farming. The mechanisms of resistance to polymyxins are mediated through intrinsic, mutational, or genetic alteration in chromosomal genes. The mechanism includes the regulatory network controlling chemical modifications of lipid A moiety of lipopolysaccharide, reducing the negative charge of lipid A and its affinity for polymyxins. Additionally, the unique mobile colistin/polymyxin B resistance (mcr) gene reported in Enterobacteriales is responsible for the horizontal dissemination of resistance to polymyxins via the food chain. There is now an urgent need to increase surveillance for detecting resistance to polymyxins. Therefore, this review presents an overview of presently available scientific literature on the mechanism of resistance to polymyxins, with their associated gene variants, evaluation methods, resistance transmission through the food chain via food bacteria, and related risk factors. We further focus on the significant implications of polymyxins usage in India and future views for food safety to preserve polymyxin activity.202235079146
487840.9999Bacteria carrying mobile colistin resistance genes and their control measures, an updated review. The plasmid encoded mobile colistin resistance (MCRs) enzyme poses a significant challenge to the clinical efficacy of colistin, which is frequently employed as a last resort antibiotic for treating infections caused by multidrug resistant bacteria. This transferase catalyzes the addition of positively charged phosphoethanolamine to lipid A of the outer membrane of gram-negative bacteria, thereby facilitating the acquired colistin resistance. This review aims to summarize and critically discuss recent advancements in the distribution and pathogenesis of mcr-positive bacteria, as well as the various control measures available for treating these infections. In addition, the ecology of mcr genes, colistin-resistance mechanism, co-existence with other antibiotic resistant genes, and their impact on clinical treatment are also analyzed to address the colistin resistance crisis. These insights provide a comprehensive perspective on MCRs and serve as a valuable reference for future therapeutic approaches to effectively combat mcr-positive bacterial infections.202439516398
487550.9998An Overview of the Genetic Mechanisms of Colistin-Resistance in Bacterial Pathogens: An Indian Perspective. Colistin resistance in bacteria is a growing global issue, given its role as a critical last-resort antibiotic, particularly for treating Gram-negative bacterial infections. Pathogens adopt multiple resistance mechanisms, mediated either by plasmids or chromosomal changes. Some of the most frequently observed strategies include the occurrence of plasmid-borne mobile colistin resistance (mcr) genes, enhanced efflux pump activity, mutations in the regulatory systems, and alterations in the lipid A structure. This article provides an overview of the studies investigating the genetic mechanisms underlying colistin resistance in nosocomial Gram-negative bacteria from India. A total of 37 studies were identified through online searches across various databases, including PubMed, ScienceDirect, and Web of Science. These studies were reviewed to examine bacterial species and their mechanisms of colistin resistance. Over 26 (70.27%) studies were focused on Klebsiella pneumoniae. The most commonly reported mechanism of colistin resistance involved mutations in the two-component systems pmrAB and phoPQ. Plasmid-mediated colistin-resistant mcr genes were identified in 22 studies (18.18%). Four studies reported the overexpression of efflux pump genes as a mechanism of colistin resistance. This article provides a comprehensive summary of these studies, emphasizing the presence of diverse resistance mechanisms across various pathogens. It underscores the necessity for future genomic research on a broader range of pathogens to investigate the prevalence of different mechanisms of colistin resistance in the various regions of India.202540078264
486660.9998Resistance to polymyxins in Gram-negative organisms. Polymyxins have recently been re-introduced into the therapeutic arsenal to combat infections caused by multidrug-resistant Gram-negative bacteria. However, the emergence of strains resistant to these last-resort drugs is becoming a critical issue in a growing number of countries. Both intrinsic and transferable mechanisms of polymyxin resistance have been characterised. These mechanisms as well as the epidemiological data regarding four relevant bacterial pathogens (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa) are considered in this review. A special focus is made on plasmid-mediated resistance and the spread of mcr genes.201728163137
486470.9998Colistin resistance mechanisms in Gram-negative bacteria: a Focus on Escherichia coli. Multidrug-resistant (MDR) Escherichia coli strains have rapidly increased worldwide, and effective antibiotic therapeutic options are becoming more restricted. As a polymyxin antibiotic, colistin has a long history of usage, and it is used as a final line of treatment for severe infections by Gram-negative bacteria (GNB) with high-level resistance. However, its application has been challenged by the emergence of E. coli colistin resistance. Hence, determining the mechanism that confers colistin resistance is crucial for monitoring and controlling the dissemination of colistin-resistant E. coli strains. This comprehensive review summarizes colistin resistance mechanisms in E. coli strains and concentrates on the history, mode of action, and therapeutic implications of colistin. We have mainly focused on the fundamental mechanisms of colistin resistance that are mediated by chromosomal or plasmid elements and discussed major mutations in the two-component systems (TCSs) genes and plasmids that transmit the mobilized colistin resistance resistant genes in E. coli strains.202336754367
487280.9998A Review on Colistin Resistance: An Antibiotic of Last Resort. Antibiotic resistance has emerged as a significant global public health issue, driven by the rapid adaptation of microorganisms to commonly prescribed antibiotics. Colistin, previously regarded as a last-resort antibiotic for treating infections caused by Gram-negative bacteria, is increasingly becoming resistant due to chromosomal mutations and the acquisition of resistance genes carried by plasmids, particularly the mcr genes. The mobile colistin resistance gene (mcr-1) was first discovered in E. coli from China in 2016. Since that time, studies have reported different variants of mcr genes ranging from mcr-1 to mcr-10, mainly in Enterobacteriaceae from various parts of the world, which is a major concern for public health. The co-presence of colistin-resistant genes with other antibiotic resistance determinants further complicates treatment strategies and underscores the urgent need for enhanced surveillance and antimicrobial stewardship efforts. Therefore, understanding the mechanisms driving colistin resistance and monitoring its global prevalence are essential steps in addressing the growing threat of antimicrobial resistance and preserving the efficacy of existing antibiotics. This review underscores the critical role of colistin as a last-choice antibiotic, elucidates the mechanisms of colistin resistance and the dissemination of resistant genes, explores the global prevalence of mcr genes, and evaluates the current detection methods for colistin-resistant bacteria. The objective is to shed light on these key aspects with strategies for combating the growing threat of resistance to antibiotics.202438674716
486590.9998Molecular mechanisms related to colistin resistance in Enterobacteriaceae. Colistin is an effective antibiotic for treatment of most multidrug-resistant Gram-negative bacteria. It is used currently as a last-line drug for infections due to severe Gram-negative bacteria followed by an increase in resistance among Gram-negative bacteria. Colistin resistance is considered a serious problem, due to a lack of alternative antibiotics. Some bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacteriaceae members, such as Escherichia coli, Salmonella spp., and Klebsiella spp. have an acquired resistance against colistin. However, other bacteria, including Serratia spp., Proteus spp. and Burkholderia spp. are naturally resistant to this antibiotic. In addition, clinicians should be alert to the possibility of colistin resistance among multidrug-resistant bacteria and development through mutation or adaptation mechanisms. Rapidly emerging bacterial resistance has made it harder for us to rely completely on the discovery of new antibiotics; therefore, we need to have logical approaches to use old antibiotics, such as colistin. This review presents current knowledge about the different mechanisms of colistin resistance.201931190901
4890100.9998Understanding of Colistin Usage in Food Animals and Available Detection Techniques: A Review. Progress in the medical profession is determined by the achievements and effectiveness of new antibiotics in the treatment of microbial infections. However, the development of multiple-drug resistance in numerous bacteria, especially Gram-negative bacteria, has limited the treatment options. Due to this resistance, the resurgence of cyclic polypeptide drugs like colistin remains the only option. The drug, colistin, is a well-known growth inhibitor of Gram-negative bacteria like Acinetobacter baumanni, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Technological advancements have uncovered the role of the mcr-1(mobilized colistin resistance) gene, which is responsible for the development of resistance in Gram-negative bacteria, which make them distinct from other bacteria without this gene. Additionally, food animals have been determined to be the reservoir for colistin resistance microbes, from which they spread to other hosts. Due to the adverse effects of colistin, many developed countries have prohibited its usage in animal foods, but developing countries are still using colistin in animal food production, thereby imposing a major risk to the public health. Therefore, there is a need for implementation of sustainable measures in livestock farms to prevent microbial infection. This review highlights the negative effects (increased resistance) of colistin consumption and emphasizes the different approaches used for detecting colistin in animal-based foods as well as the challenges associated with its detection.202033081121
4871110.9998Colistin: from the shadows to a One Health approach for addressing antimicrobial resistance. Antimicrobial resistance (AMR) poses a serious threat to human, animal and environmental health worldwide. Colistin has regained importance as a last-resort treatment against multi-drug-resistant Gram-negative bacteria. However, colistin resistance has been reported in various Enterobacteriaceae species isolated from several sources. The 2015 discovery of the plasmid-mediated mcr-1 (mobile colistin resistance) gene conferring resistance to colistin was a major concern within the scientific community worldwide. The global spread of this plasmid - as well as the subsequent identification of 10 MCR-family genes and their variants that catalyse the addition of phosphoethanolamine to the phosphate group of lipid A - underscores the urgent need to regulate the use of colistin, particularly in animal production. This review traces the history of colistin resistance and mcr-like gene identification, and examines the impact of policy changes regarding the use of colistin on the prevalence of mcr-1-positive Escherichia coli and colistin-resistant E. coli from a One Health perspective. The withdrawal of colistin as a livestock growth promoter in several countries reduced the prevalence of colistin-resistant bacteria and its resistance determinants (e.g. mcr-1 gene) in farm animals, humans and the environment. This reduction was certainly favoured by the significant fitness cost associated with acquisition and expression of the mcr-1 gene in enterobacterial species. The success of this One Health intervention could be used to accelerate regulation of other important antimicrobials, especially those associated with bacterial resistance mechanisms linked to high fitness cost. The development of global collaborations and the implementation of sustainable solutions like the One Health approach are essential to manage AMR.202336640846
4883120.9998New tools to mitigate drug resistance in Enterobacteriaceae - Escherichia coli and Klebsiella pneumoniae. Treatment to common bacterial infections are becoming ineffective of late, owing to the emergence and dissemination of antibiotic resistance globally. Escherichia coli and Klebsiella pneumoniae are the most notorious microorganisms and are among the critical priority pathogens listed by WHO in 2017. These pathogens are the predominant cause of sepsis, urinary tract infections (UTIs), pneumonia, meningitis and pyogenic liver abscess. Concern arises due to the resistance of bacteria to most of the beta lactam antibiotics like penicillin, cephalosporin, monobactams and carbapenems, even to the last resort antibiotics like colistin. Preventing influx by modulation of porins, extruding the antibiotics by overexpression of efflux pumps, mutations of drug targets/receptors, biofilm formation, altering the drug molecules and rendering them ineffective are few resistance mechanisms that are adapted by Enterobacteriaeceae upon exposure to antibiotics. The situation is exacerbated due to the process of horizontal gene transfer (HGT), wherein the genes encoding resistance mechanisms are transferred to the neighbouring bacteria through plasmids/phages/uptake of free DNA. Carbapenemases, other beta lactamases and mcr genes coding for colistin resistance are widely disseminated leading to limited/no therapeutic options against those infections. Development of new antibiotics can be viewed as a possible solution but it involves major investment, time and labour despite which, the bacteria can easily adapt to the new antibiotic and evolve resistance in a relatively short time. Targeting the resistance mechanisms can be one feasible alternative to tackle these multidrug resistant (MDR) pathogens. Removal of plasmid (plasmid curing) causing resistance, use of bacteriophages and bacteriotherapy can be other potential approaches to combat infections caused by MDR E. coli and K. pneumoniae. The present review discusses the efficacies of these therapies in mitigating these infections, which can be potentially used as an adjuvant therapy along with existing antibiotics.202335649163
4887130.9998Mechanisms of Bacterial Drug Resistance with Special Emphasis on Phenotypic and Molecular Characterization of Extended Spectrum Beta-lactamase. Antibiotics are designed to effectively treat bacterial infections while minimizing harm to the human body. They work by targeting specific components of bacteria or by disrupting essential processes such as cell wall synthesis, membrane function, protein production, and metabolic pathways. However, the misuse and overuse of antibiotics have led to the emergence of drug resistance in humans, animals, and agriculture, contributing to the global spread of this problem. Drug resistance can be either innate or acquired, with acquired resistance involving changes in the bacterial chromosomes or transferable elements. Bacterial species employ various mechanisms of drug resistance, including modifying the antibiotic targets, inactivating the drug, reducing uptake or increasing efflux, overexpressing the target, utilizing alternative pathways, and forming biofilms. One significant concern in the realm of drug resistance revolves around the emergence and proliferation of extended-spectrum beta-lactamases (ESBLs), a gene that is found in most gram-negative bacteria, primarily carried by Escherichia coli and Klebsiella pneumoniae in healthcare settings. ESBL-mediated resistance poses challenges for diagnosis, treatment, infection control, and antibiotic stewardship. Accurate detection of ESBL genes is crucial, and phenotypic methods are commonly used for initial screening. However, these methods have limitations, and confirmatory molecular techniques such as PCR and DNA sequencing are employed to accurately identify ESBL genes. Despite the significant global concerns surrounding ESBLs, they have spread worldwide, mainly facilitated by healthcare settings, inappropriate antimicrobial use, and host susceptibility. Addressing this issue requires implementing comprehensive measures, including enhanced surveillance, strict infection control practices, antibiotic stewardship programs, rapid diagnostic methods, alternative therapies, public education initiatives, and research focused on developing new drugs. Furthermore, collaboration among the healthcare, public health, and research sectors is pivotal in effectively combating the escalating threat posed by ESBL-mediated resistance. Antibiotics have revolutionized medical care by effectively treating bacterial infections. However, the emergence of ESBL gene resistance poses a global challenge that requires an integrated approach to prevent a threatening future.202438700878
4882140.9998Molecular Factors and Mechanisms Driving Multidrug Resistance in Uropathogenic Escherichia coli-An Update. The rapid emergence of multidrug-resistant (MDR) bacteria indisputably constitutes a major global health problem. Pathogenic Escherichia coli are listed among the most critical group of bacteria that require fast development of new antibiotics and innovative treatment strategies. Among harmful extraintestinal Enterobacteriaceae strains, uropathogenic E. coli (UPEC) pose a significant health threat. UPEC are considered the major causative factor of urinary tract infection (UTI), the second-most commonly diagnosed infectious disease in humans worldwide. UTI treatment places a substantial financial burden on healthcare systems. Most importantly, the misuse of antibiotics during treatment has caused selection of strains with the ability to acquire MDR via miscellaneous mechanisms resulting in gaining resistance against many commonly prescribed antibiotics like ampicillin, gentamicin, cotrimoxazole and quinolones. Mobile genetic elements (MGEs) such as transposons, integrons and conjugative plasmids are the major drivers in spreading resistance genes in UPEC. The co-occurrence of various bacterial evasion strategies involving MGEs and the SOS stress response system requires further research and can potentially lead to the discovery of new, much-awaited therapeutic targets. Here, we analyzed and summarized recent discoveries regarding the role, mechanisms, and perspectives of MDR in the pathogenicity of UPEC.202236011308
4822150.9998A Molecular Perspective on Colistin and Klebsiella pneumoniae: Mode of Action, Resistance Genetics, and Phenotypic Susceptibility. Klebsiella pneumoniae is a rod-shaped, encapsulated, Gram-negative bacteria associated with multiple nosocomial infections. Multidrug-resistant (MDR) K. pneumoniae strains have been increasing and the therapeutic options are increasingly limited. Colistin is a long-used, polycationic, heptapeptide that has regained attention due to its activity against Gram-negative bacteria, including the MDR K. pneumoniae strains. However, this antibiotic has a complex mode of action that is still under research along with numerous side-effects. The acquisition of colistin resistance is mainly associated with alteration of lipid A net charge through the addition of cationic groups synthesized by the gene products of a multi-genic regulatory network. Besides mutations in these chromosomal genes, colistin resistance can also be achieved through the acquisition of plasmid-encoded genes. Nevertheless, the diversity of molecular markers for colistin resistance along with some adverse colistin properties compromises the reliability of colistin-resistance monitorization methods. The present review is focused on the colistin action and molecular resistance mechanisms, along with specific limitations on drug susceptibility testing for K. pneumoniae.202134202395
4873160.9998Farm animals and aquaculture: significant reservoirs of mobile colistin resistance genes. Colistin resistance has attracted substantial attention after colistin was considered as a last-resort drug for the treatment of infections caused by carbapenem-resistant and/or multidrug-resistant (MDR) Gram-negative bacteria in clinical settings. However, with the discovery of highly mobile colistin resistance (mcr) genes, colistin resistance has become an increasingly urgent issue worldwide. Despite many reviews, which summarized the prevalence, mechanisms, and structures of these genes in bacteria of human and animal origin, studies on the prevalence of mobile colistin resistance genes in aquaculture and their transmission between animals and humans remain scarce. Herein, we review recent reports on the prevalence of colistin resistance genes in animals, especially wildlife and aquaculture, and their possibility of transmission to humans via the food chain. This review also gives some insights into the routine surveillance, changing policy and replacement of polymyxins by polymyxin derivatives, molecular inhibitors, and traditional Chinese medicine to tackle colistin resistance.202032114703
4861170.9998The Challenge of Global Emergence of Novel Colistin-Resistant Escherichia coli ST131. Escherichia coli ST131 is one of the high-risk multidrug-resistant clones with a global distribution and the ability to persist and colonize in a variety of niches. Carbapenemase-producing E. coli ST131 strains with the ability to resist last-line antibiotics (i.e., colistin) have been recently considered a significant public health. Colistin is widely used in veterinary medicine and therefore, colistin-resistant bacteria can be transmitted from livestock to humans through food. There are several mechanisms of resistance to colistin, which include chromosomal mutations and plasmid-transmitted mcr genes. E. coli ST131 is a great model organism to investigate the emergence of superbugs. This microorganism has the ability to cause intestinal and extraintestinal infections, and its accurate identification as well as its antibiotic resistance patterns are vitally important for a successful treatment strategy. Therefore, further studies are required to understand the evolution of this resistant organism for drug design, controlling the evolution of other nascent emerging pathogens, and developing antibiotic stewardship programs. In this review, we will discuss the importance of E. coli ST131, the mechanisms of resistance to colistin as the last-resort antibiotic against resistant Gram-negative bacteria, reports from different regions regarding E. coli ST131 resistance to colistin, and the most recent therapeutic approaches against colistin-resistance bacteria.202133913748
4868180.9998Extended spectrum β-lactamases, carbapenemases and mobile genetic elements responsible for antibiotics resistance in Gram-negative bacteria. Infectious diseases due to Gram-negative bacteria are a leading cause of morbidity and mortality worldwide. Antimicrobial agents represent one major therapeutic tools implicated to treat these infections. The misuse of antimicrobial agents has resulted in the emergence of resistant strains of Gram-negatives in particular Enterobacteriaceae and non-fermenters; they have an effect not only on a human but on the public health when bacteria use the resistance mechanisms to spread in the hospital environment and to the community outside the hospitals by means of mobile genetic elements. Gram-negative bacteria have become increasingly resistant to antimicrobial agents. They have developed several mechanisms by which they can withstand to antimicrobials, these mechanisms include the production of Extended-spectrum β-lactamases (ESBLs) and carbapenemases, furthermore, Gram-negative bacteria are now capable of spreading such resistance between members of the family Enterobacteriaceae and non-fermenters using mobile genetic elements as vehicles for such resistance mechanisms rendering antibiotics useless. Therefore, addressing the issue of mechanisms of antimicrobial resistance is considered one of most urgent priorities. This review will help to illustrate different resistance mechanisms; ESBLs, carbapenemases encoded by genes carried by mobile genetic elements, which are used by Gram-negative bacteria to escape antimicrobial effect.201322667455
4862190.9998Genetic Factors That Contribute to Antibiotic Resistance through Intrinsic and Acquired Bacterial Genes in Urinary Tract Infections. The overprescribing and misuse of antibiotics have led to the rapid development of multidrug-resistant bacteria, such as those that cause UTIs. UTIs are the most common outpatient infections and are mainly caused by Escherichia coli and Klebsiella spp., although some Gram-positive bacteria, such as Pseudomonas aeruginosa, have been isolated in many cases. The rise of antimicrobial-resistant bacteria is a major public health concern, as it is predicted to lead to increased healthcare costs and poor patient outcomes and is expected to be the leading cause of global mortality by 2050. Antibiotic resistance among bacterial species can arise from a myriad of factors, including intrinsic and acquired resistance mechanisms, as well as mobile genetic elements, such as transposons, integrons, and plasmids. Plasmid-mediated resistance is of major concern as drug-resistance genes can quickly and efficiently spread across bacterial species via horizontal gene transfer. The emergence of extended-spectrum β-lactamases (ESBLs) such as NDM-1, OXA, KPC, and CTX-M family members has conferred resistance to many commonly used antibiotics in the treatment of UTIs, including penicillins, carbapenems, cephalosporins, and sulfamethoxazole. This review will focus on plasmid-mediated bacterial genes, especially those that encode ESBLs, and how they contribute to antibiotic resistance. Early clinical detection of these genes in patient samples will provide better treatment options and reduce the threat of antibiotic resistance.202337374909