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985500.9974Conjugative IncC Plasmid Entry Triggers the SOS Response and Promotes Effective Transfer of the Integrative Antibiotic Resistance Element SGI1. The broad-host-range IncC plasmid family and the integrative mobilizable Salmonella genomic island 1 (SGI1) and its derivatives enable the spread of medically important antibiotic resistance genes among Gram-negative pathogens. Although several aspects of the complex functional interactions between IncC plasmids and SGI1 have been recently deciphered regarding their conjugative transfer and incompatibility, the biological signal resulting in the hijacking of the conjugative plasmid by the integrative mobilizable element remains unknown. Here, we demonstrate that the conjugative entry of IncC/IncA plasmids is detected at an early stage by SGI1 through the transient activation of the SOS response, which induces the expression of the SGI1 master activators SgaDC, shown to play a crucial role in the complex biology between SGI1 and IncC plasmids. Besides, we developed an original tripartite conjugation approach to directly monitor SGI1 mobilization in a time-dependent manner following conjugative entry of IncC plasmids. Finally, we propose an updated biological model of the conjugative mobilization of the chromosomal resistance element SGI1 by IncC plasmids. IMPORTANCE Antimicrobial resistance has become a major public health issue, particularly with the increase of multidrug resistance (MDR) in both animal and human pathogenic bacteria and with the emergence of resistance to medically important antibiotics. The spread between bacteria of successful mobile genetic elements, such as conjugative plasmids and integrative elements conferring multidrug resistance, is the main driving force in the dissemination of acquired antibiotic resistances among Gram-negative bacteria. Broad-host-range IncC plasmids and their integrative mobilizable SGI1 counterparts contribute to the spread of critically important resistance genes (e.g., extended-spectrum β-lactamases [ESBLs] and carbapenemases). A better knowledge of the complex biology of these broad-host-range mobile elements will help us to understand the dissemination of antimicrobial resistance genes that occurred across Gammaproteobacteria borders.202336472437
416010.9973The association between the genetic structures of commonly incompatible plasmids in Gram-negative bacteria, their distribution and the resistance genes. Incompatible plasmids play a crucial role in the horizontal transfer of antibiotic resistance in bacteria, particularly in Gram-negative bacteria, and have thus attracted considerable attention in the field of microbiological research. In the 1970s, these plasmids, housing an array of resistance genes and genetic elements, were predominantly discovered. They exhibit a broad presence in diverse host bacteria, showcasing diversity in geographic distribution and the spectrum of antibiotic resistance genes. The complex genetic structure of plasmids further accelerates the accumulation of resistance genes in Gram-negative bacteria. This article offers a comprehensive review encompassing the discovery process, host distribution, geographic prevalence, carried resistance genes, and the genetic structure of different types incompatible plasmids, including IncA, IncC, IncF, IncL, IncM, IncH, and IncP. It serves as a valuable reference for enhancing our understanding of the role of these different types of plasmids in bacterial evolution and the dissemination of antibiotic resistance.202439660283
378420.9973Insight into the mobilome of Aeromonas strains. The mobilome is a pool of genes located within mobile genetic elements (MGE), such as plasmids, IS elements, transposons, genomic/pathogenicity islands, and integron-associated gene cassettes. These genes are often referred to as "flexible" and may encode virulence factors, toxic compounds as well as resistance to antibiotics. The phenomenon of MGE transfer between bacteria, known as horizontal gene transfer (HGT), is well documented. The genes present on MGE are subject to continuous processes of evolution and environmental changes, largely induced or significantly accelerated by man. For bacteria, the only chance of survival in an environment contaminated with toxic chemicals, heavy metals and antibiotics is the acquisition of genes providing the ability to survive in such conditions. The process of acquiring and spreading antibiotic resistance genes (ARG) is of particular significance, as it is important for the health of humans and animals. Therefore, it is important to thoroughly study the mobilome of Aeromonas spp. that is widely distributed in various environments, causing many diseases in fishes and humans. This review discusses the recently published information on MGE prevalent in Aeromonas spp. with special emphasis on plasmids belonging to different incompatibility groups, i.e., IncA/C, IncU, IncQ, IncF, IncI, and ColE-type. The vast majority of plasmids carry a number of different transposons (Tn3, Tn21, Tn1213, Tn1721, Tn4401), the 1st, 2nd, or 3rd class of integrons, IS elements (e.g., IS26, ISPa12, ISPa13, ISKpn8, ISKpn6) and encode determinants such as antibiotic and mercury resistance genes, as well as virulence factors. Although the actual role of Aeromonas spp. as a human pathogen remains controversial, species of this genus may pose a serious risk to human health. This is due to the considerable potential of their mobilome, particularly in terms of antibiotic resistance and the possibility of the horizontal transfer of resistance genes.201526074893
990430.9973Genome plasticity as a paradigm of antibiotic resistance spread in ESKAPE pathogens. The major reason behind the spread of antibiotic resistance genes (ARGs) is persistent selective pressure in the environment encountered by bacteria. Genome plasticity plays a crucial role in dissemination of antibiotic resistance among bacterial pathogens. Mobile genetic elements harboring ARGs are reported to dodge bacterial immune system and mediate horizontal gene transfer (HGT) under selective pressure. Residual antibiotic pollutants develop selective pressures that force the bacteria to lose their defense mechanisms (CRISPR-cas) and acquire resistance. The present study targets the ESKAPE organisms (namely, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) causing various nosocomial infections and emerging multidrug-resistant species. The role of CRISPR-cas systems in inhibition of HGT in prokaryotes and its loss due to presence of various stressors in the environment is also focused in the study. IncF and IncH plasmids were identified in all strains of E. faecalis and K. pneumoniae, carrying Beta-lactam and fluoroquinolone resistance genes, whereas sal3, phiCTX, and SEN34 prophages harbored aminoglycoside resistance genes (aadA, aac). Various MGEs present in selected environmental niches that aid the bacterial genome plasticity and transfer of ARGs contributing to its spread are also identified.202235349073
971940.9973Dynamics of antibiotic resistance genes in plasmids and bacteriophages. This brief review explores the intricate interplay between bacteriophages and plasmids in the context of antibiotic resistance gene (ARG) dissemination. Originating from studies in the late 1950s, the review traces the evolution of knowledge regarding extrachromosomal factors facilitating horizontal gene transfer and adaptation in bacteria. Analyzing the gene repertoires of plasmids and bacteriophages, the study highlights their contributions to bacterial evolution and adaptation. While plasmids encode essential and accessory genes influencing host characteristics, bacteriophages carry auxiliary metabolic genes (AMGs) that augment host metabolism. The debate on phages carrying ARGs is explored through a critical evaluation of various studies, revealing contrasting findings from researchers. Additionally, the review addresses the interplay between prophages and plasmids, underlining their similarities and divergences. Based on the available literature evidence, we conclude that plasmids generally encode ARGs while bacteriophages typically do not contain ARGs. But extra-chromosomaly present prophages with plasmid characteristics can encode and disseminate ARGs.202538651513
986150.9972Comparative genomics of native plasmids from plant pathogenic Gammaproteobacteria. Plasmids are key in the evolution and adaptation of plant pathogenic Gammaproteobacteria (PPG), yet their diversity and functional contributions remain underexplored. Here, comparative genomics revealed extensive variation in plasmid size, replicon types, mobility, and genetic content across PPG. Most plasmids are small (< 200 kb), except in Pantoea, exhibiting high coding densities (76% to 78%). Five ancestral replicon types were identified across multiple orders, indicating vertical descent yet efficient horizontal transfer across taxa, although with limited genetic conservation. Virulence plasmids are widespread (56% to 68%) but differ in virulence gene content across orders: type III effector (T3E) genes are common in Pseudomonas and Xanthomonas, but rare in Enterobacterales and Xylella, aligning with their smaller effector repertoires. Plasmids frequently carry regulatory genes, highlighting their role in bacterial phenotype modulation. Distinct patterns were observed among orders: Enterobacterales plasmids often harbor thiamin biosynthesis operons and transcriptional regulators but lack post-transcriptional regulators, while most Pseudomonas and Xanthomonas plasmids are mobile, enriched in T3E genes, and exhibit high insertion sequence densities, fostering DNA mobility. Resistance to ultraviolet light is common, but not to antimicrobial compounds. These findings highlight the dynamic role of plasmids in spreading adaptive traits, shaping virulence, and driving the evolution of plant pathogenic bacteria.202540273218
333760.9972Evidence for wastewaters as environments where mobile antibiotic resistance genes emerge. The emergence and spread of mobile antibiotic resistance genes (ARGs) in pathogens have become a serious threat to global health. Still little is known about where ARGs gain mobility in the first place. Here, we aimed to collect evidence indicating where such initial mobilization events of clinically relevant ARGs may have occurred. We found that the majority of previously identified origin species did not carry the mobilizing elements that likely enabled intracellular mobility of the ARGs, suggesting a necessary interplay between different bacteria. Analyses of a broad range of metagenomes revealed that wastewaters and wastewater-impacted environments had by far the highest abundance of both origin species and corresponding mobilizing elements. Most origin species were only occasionally detected in other environments. Co-occurrence of origin species and corresponding mobilizing elements were rare in human microbiota. Our results identify wastewaters and wastewater-impacted environments as plausible arenas for the initial mobilization of resistance genes.202336966231
404870.9972Mobile genetic elements in the genus Bacteroides, and their mechanism(s) of dissemination. Bacteroides spp organisms, the predominant commensal bacteria in the human gut have become increasingly resistant to many antibiotics. They are now also considered to be reservoirs of antibiotic resistance genes due to their capacity to harbor and disseminate these genes via mobile transmissible elements that occur in bewildering variety. Gene dissemination occurs within and from Bacteroides spp primarily by conjugation, the molecular mechanisms of which are still poorly understood in the genus, even though the need to prevent this dissemination is urgent. One current avenue of research is thus focused on interventions that use non-antibiotic methodologies to prevent conjugation-based DNA transfer.201122479685
925480.9972Horizontal gene transfer in human pathogens. Horizontal gene transfer has a tremendous impact on the genome plasticity, adaptation and evolution of bacteria. Horizontally transferred mobile genetic elements are involved in the dissemination of antibiotic resistance and virulence genes, thus contributing to the emergence of novel "superbugs". This review provides update on various mechanisms of horizontal gene transfer and examines how horizontal gene transfer contributes to the evolution of pathogenic bacteria. Special focus is paid to the role horizontal gene transfer plays in pathogenicity of the emerging human pathogens: hypervirulent Clostridium difficile and Escherichia coli (including the most recent haemolytic uraemic syndrome outbreak strain) and methicillin-resistant Staphylococcus aureus (MRSA), which have been associated with largest outbreaks of infection recently.201523862575
400690.9972Targeting Plasmids to Limit Acquisition and Transmission of Antimicrobial Resistance. Antimicrobial resistance (AMR) is a significant global threat to both public health and the environment. The emergence and expansion of AMR is sustained by the enormous diversity and mobility of antimicrobial resistance genes (ARGs). Different mechanisms of horizontal gene transfer (HGT), including conjugation, transduction, and transformation, have facilitated the accumulation and dissemination of ARGs in Gram-negative and Gram-positive bacteria. This has resulted in the development of multidrug resistance in some bacteria. The most clinically significant ARGs are usually located on different mobile genetic elements (MGEs) that can move intracellularly (between the bacterial chromosome and plasmids) or intercellularly (within the same species or between different species or genera). Resistance plasmids play a central role both in HGT and as support elements for other MGEs, in which ARGs are assembled by transposition and recombination mechanisms. Considering the crucial role of MGEs in the acquisition and transmission of ARGs, a potential strategy to control AMR is to eliminate MGEs. This review discusses current progress on the development of chemical and biological approaches for the elimination of ARG carriers.202032435238
4009100.9972Unraveling the role of mobile genetic elements in antibiotic resistance transmission and defense strategies in bacteria. Irrational antibiotic use contributes to the development of antibiotic resistance in bacteria, which is a major cause of healthcare-associated infections globally. Molecular research has shown that multiple resistance frequently develops from the uptake of pre-existing resistance genes, which are subsequently intensified under selective pressures. Resistant genes spread and are acquired through mobile genetic elements which are essential for facilitating horizontal gene transfer. MGEs have been identified as carriers of genetic material and are a significant player in evolutionary processes. These include insertion sequences, transposons, integrative and conjugative elements, plasmids, and genomic islands, all of which can transfer between and within DNA molecules. With an emphasis on pathogenic bacteria, this review highlights the salient features of the MGEs that contribute to the development and spread of antibiotic resistance. MGEs carry non-essential genes, including AMR and virulence genes, which can enhance the adaptability and fitness of their bacterial hosts. These elements employ evolutionary strategies to facilitate their replication and dissemination, thus enabling survival without positive selection for the harboring of beneficial genes.202540810119
4092110.9972Vertical transfer of antibiotics and antibiotic resistant strains across the mother/baby axis. Antibiotic resistance is a health and socioeconomic crisis recognized as a serious threat affecting humans worldwide. Overuse of antibiotics enhances the spread of multidrug-resistant bacteria, causing drug-resistant infections which can be difficult to treat. This resistance, mostly of the acquired type, is thus a major clinical issue. Acquired resistance can occur by horizontal transfer of genes between bacteria (community settings), by vertical transmission that can occur between mother and her offspring at birth and during lactation, or spontaneously due to antibiotic exposure. While there have been multiple studies about the horizontal transfer of antibiotic-resistance genes, not many studies have been conducted to study their vertical transmission. Vertical transmission is of importance as the early bacterial colonization of infants has an impact on their health and immune programming throughout life. This review discusses some possible mechanisms of mother-to-infant transmission of antibiotics and antibiotic-resistant strains and addresses the knowledge gaps for further studies.202234172345
4161120.9972Integron and its role in antimicrobial resistance: A literature review on some bacterial pathogens. In recent years, different acquired resistance mechanisms, including transposons, bacteriophages, plasmids, and integrons have been identified as involved in the spread of resistance genes in bacteria. The role of integrons as mobile genetic elements playing a central role in antibiotic resistance has been well studied and documented. Integrons are the ancient structures that mediate the evolution of bacteria by acquiring, storing, disposing, and resorting to the reading frameworks in gene cassettes. The term integron describes a large family of genetic elements, all of which are able to capture gene cassettes. Integrons were classified into three important classes based on integrase intI gene sequence. Integrons can carry and spread the antibiotic resistance genes among bacteria and are among the most significant routes of distribution of resistance genes via horizontal transfer. All integrons have three essential core features. The first feature is intI, the second one is an integron-associated recombination site, attI, and an integron-associated promoter, Pc, is the last feature. Among them, the class 1 integron is a major player in the dissemination of antibiotic resistance genes across pathogens and commensals. Various classes of integrons possessing a wide variety of gene cassettes are distributed in bacteria throughout the world. This review thus focuses on the distribution of integrons among important bacteria.202133953851
9650130.9972Plasmid-Encoded Traits Vary across Environments. Plasmids are key mobile genetic elements in bacterial evolution and ecology as they allow the rapid adaptation of bacteria under selective environmental changes. However, the genetic information associated with plasmids is usually considered separately from information about their environmental origin. To broadly understand what kinds of traits may become mobilized by plasmids in different environments, we analyzed the properties and accessory traits of 9,725 unique plasmid sequences from a publicly available database with known bacterial hosts and isolation sources. Although most plasmid research focuses on resistance traits, such genes made up <1% of the total genetic information carried by plasmids. Similar to traits encoded on the bacterial chromosome, plasmid accessory trait compositions (including general Clusters of Orthologous Genes [COG] functions, resistance genes, and carbon and nitrogen genes) varied across seven broadly defined environment types (human, animal, wastewater, plant, soil, marine, and freshwater). Despite their potential for horizontal gene transfer, plasmid traits strongly varied with their host's taxonomic assignment. However, the trait differences across environments of broad COG categories could not be entirely explained by plasmid host taxonomy, suggesting that environmental selection acts on the plasmid traits themselves. Finally, some plasmid traits and environments (e.g., resistance genes in human-related environments) were more often associated with mobilizable plasmids (those having at least one detected relaxase) than others. Overall, these findings underscore the high level of diversity of traits encoded by plasmids and provide a baseline to investigate the potential of plasmids to serve as reservoirs of adaptive traits for microbial communities. IMPORTANCE Plasmids are well known for their role in the transmission of antibiotic resistance-conferring genes. Beyond human and clinical settings, however, they disseminate many other types of genes, including those that contribute to microbially driven ecosystem processes. In this study, we identified the distribution of traits genetically encoded by plasmids isolated from seven broadly categorized environments. We find that plasmid trait content varied with both bacterial host taxonomy and environment and that, on average, half of the plasmids were potentially mobilizable. As anthropogenic activities impact ecosystems and the climate, investigating and identifying the mechanisms of how microbial communities can adapt will be imperative for predicting the impacts on ecosystem functioning.202336629415
9836140.9972Staphylococcus aureus mobile genetic elements. Among the bacteria groups, most of them are known to be beneficial to human being whereas only a minority is being recognized as harmful. The pathogenicity of bacteria is due, in part, to their rapid adaptation in the presence of selective pressures exerted by the human host. In addition, through their genomes, bacteria are subject to mutations, various rearrangements or horizontal gene transfer among and/or within bacterial species. Bacteria's essential metabolic functions are generally encoding by the core genes. Apart of the core genes, there are several number of mobile genetic elements (MGE) acquired by horizontal gene transfer that might be beneficial under certain environmental conditions. These MGE namely bacteriophages, transposons, plasmids, and pathogenicity islands represent about 15% Staphylococcus aureus genomes. The acquisition of most of the MGE is made by horizontal genomic islands (GEI), recognized as discrete DNA segments between closely related strains, transfer. The GEI contributes to the wide spread of microorganisms with an important effect on their genome plasticity and evolution. The GEI are also involve in the antibiotics resistance and virulence genes dissemination. In this review, we summarize the mobile genetic elements of S. aureus.201424728610
6692150.9972An omics-based framework for investigating the emerging antibiotic resistance gene: The case of estT. The escalating prevalence of antimicrobial resistance (AMR) constitutes a global public health crisis. This is exacerbated by the continuous emergence of new variants and the discovery of previously unrecognized antibiotic resistance genes (ARGs). While advanced AMR surveillance efforts include time-consuming epidemiological investigations and retrospective analyses, critical gaps often remain towards our understanding of the sources of newly identified ARGs. Here, we established a framework integrating omics-based epidemiological investigations, genomic feature analysis of ARGs-carrying bacteria and evolution analysis of novel ARGs. We took the novel resistance gene estT as an example and analyzed it following this framework. Our study revealed that the estT gene was widely prevalent, capable of cross-phyla transmission, and predominantly present in human- and animal-derived bacteria. We explored the genomic characteristics of estT-positive Escherichia coli, Bacillus spp., Mannheimia haemolytica, and Riemerella anatipestifer, uncovering their public health risks. Evolution analysis of estT homologs found historical connections between estTs and tet(X)s. This study provides a systematic strategy for the proactive surveillance of emerging ARGs, enabling omics-data-driven monitoring of ARG evolution and dissemination to mitigate the escalating crisis of AMR.202541160932
4013160.9972Correlation between Exogenous Compounds and the Horizontal Transfer of Plasmid-Borne Antibiotic Resistance Genes. The global spread of antibiotic resistance has posed a serious threat to public healthcare and undermined decades of progress made in the fight against bacterial infections. It has been demonstrated that the lack of novel effective antibiotics and rapid spread of antibiotic resistance genes via horizontal transfer in the ecosystem are mainly responsible for this crisis. Notably, plasmid-mediated horizontal transfer of antibiotic resistance genes (ARGs) is recognized as the most dominant dissemination pathway of ARGs in humans, animals and environmental settings. Antibiotic selective pressure has always been regarded as one of the crucial contributors to promoting the dissemination of antibiotic resistance through horizontal gene transfer (HGT). However, the roles of exogenous compounds and particularly non-antibiotic drugs in the spread of ARGs are still underappreciated. In this review, we first summarize the major pathways of HGT in bacteria, including conjugation, transformation, transduction and vesiduction. Subsequently, an overview of these compounds capable of promoting the HGT is presented, which guides to the formulation of more reasonable dosing regimens and drug residue standards in clinical practice. By contrast, these compounds that display an inhibition effect on HGT are also highlighted, which provides a unique strategy to minimize the spread of ARGs. Lastly, we discuss the implementations and challenges in bringing these HGT inhibitors into clinical trials.202032784449
9838170.9972Interactions between plasmids and other mobile genetic elements affect their transmission and persistence. Plasmids are genetic elements that play a role in bacterial evolution by providing new genes that promote adaptation to diverse conditions. Plasmids are also known to reduce bacterial competitiveness in the absence of selection for plasmid-encoded traits. It is easier to understand plasmid persistence when considering the evidence that plasmid maintenance can improve during co-evolution with the bacterial host, i.e. the chromosome. However, bacteria isolated from nature often harbor diverse mobile elements: phages, transposons, genomic islands and even other plasmids. Recent interest has emerged on the role such elements play on the persistence and evolution of plasmids. Here, we mainly review interactions between different plasmids, but also discuss their interactions with other genetic elements. We focus on interactions that impact fundamental plasmid traits, such as the fitness effect imposed on their hosts and the transfer efficiency into new host cells. We illustrate these phenomena with examples concerning clinically relevant organisms and the spread of plasmids carrying antibiotic resistance genes and virulence factors.201930771401
3780180.9972Is ICE hot? A genomic comparative study reveals integrative and conjugative elements as "hot" vectors for the dissemination of antibiotic resistance genes. Different from other extensively studied mobile genetic elements (MGEs) whose discoveries were initiated decades ago (1950s-1980s), integrative and conjugative elements (ICEs), a diverse array of more recently identified elements that were formally termed in 2002, have aroused increasing concern for their crucial contribution to the dissemination of antibiotic resistance genes (ARGs). However, the comprehensive understanding on ICEs' ARG profile across the bacterial tree of life is still blurred. Through a genomic study by comparison with two key MGEs, we, for the first time, systematically investigated the ARG profile as well as the host range of ICEs and also explored the MGE-specific potential to facilitate ARG propagation across phylogenetic barriers. These findings could serve as a theoretical foundation for risk assessment of ARGs mediated by distinct MGEs and further to optimize therapeutic strategies aimed at restraining antibiotic resistance crises.202338032189
9946190.9972Genomic insights into plasmid-mediated antimicrobial resistance in the bacterium Bhargavaea beijingensis strain PS04. The dissemination of antimicrobial-resistant bacteria through environment is a major health concern for public health. Pathogenic bacteria in natural environment can mediate the transfer of antimicrobial-resistant genes via horizontal gene transfer to naturally occurring bacteria in the soil. Bhargavaea beijingensis is a Gram-negative bacterium that is commonly found in soil and water. In recent years, there has been an emergence of antibiotic-resistant strains of environmental bacteria, which pose a significant threat to human health. One mechanism of antibiotic resistance in bacteria is through the acquisition of plasmids, which can carry genes that confer resistance to various antibiotics. In this study, a novel plasmid of repUS12 replicon type was identified in the strain PS04 of B. beijingensis, which carried the ermT and tet(L) genes, encoding resistance to macrolides, lincosamides, and tetracycline. The plasmid was found to be the first of its kind in B. beijingensis and was thought to have been acquired through horizontal gene transfer. The emergence of plasmid-mediated resistance in B. beijingensis highlights the need for continued surveillance and monitoring of antibiotic resistance in environmental bacteria.202338133813