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677200.9991Disinfectants facilitate the transformation of exogenous antibiotic resistance genes via multiple pathways. The prevalence and spread of multidrug-resistant (MDR) bacteria pose a global challenge to public health. Natural transformation is one of the essential ways for horizontal transfer of antibiotic resistance genes (ARGs). Although disinfectants are frequently used during COVID-19, little is known about whether these disinfectants are associated with the transformation of plasmid-borne ARGs. In our study, we assessed the effect of some disinfectants on bacterial transformation using resistance plasmids as extracellular DNA and E. coli DH5α as the recipient bacteria. The results showed that these disinfectants at environmentally relevant concentrations, including benzalkonium bromide (BB), benzalkonium chloride (BC) and polyhexamethylene guanidine hydrochloride (PHMG), significantly enhanced the transformation of plasmid-encoded ARGs. Furthermore, we investigated the mechanisms underlying the promotive effect of disinfectants on transformation. We revealed that the addition of disinfectants significantly increased the membrane permeability and promoted membrane-related genes expression. Moreover, disinfectants led to the boosted bacterial respiration, ATP production and flagellum motility, as well as increased expression of bacterial secretion system-related genes. Together, our findings shed insights into the spread of ARGs through bacterial transformation and indicate potential risks associated with the widespread use of disinfectants.202336857920
924610.9991Horizontal Gene Transfer Systems for Spread of Antibiotic Resistance in Gram-Negative Bacteria. Antibiotic-resistant bacteria have become a significant global threat to public health due to the increasing difficulty in treatment. These bacteria acquire resistance by incorporating various antibiotic resistance genes (ARGs) through specialized gene transfer mechanisms, allowing them to evade antibiotic attacks. Conjugation, transformation, and transduction are well-established mechanisms that drive the acquisition and dissemination of ARGs in Gram-negative bacteria. In particular, the horizontal transfer of plasmids carrying multiple ARGs is highly problematic, as it can instantly convert susceptible bacteria into multidrug-resistant ones. Transduction, mediated by bacteriophages that package ARG-containing chromosomal DNA from host cells, also plays a crucial role in ARG spread without requiring direct cell-to-cell contact. Recently, a novel horizontal gene transfer (HGT) mechanism involving outer membrane vesicles (OMVs) has been identified as a key player in ARG dissemination. OMVs-nanoscale, spherical structures produced by bacteria during growth-have been found to carry small plasmids and chromosomal DNA fragments containing ARGs from their host bacteria. This newly discovered transfer process, termed "vesiduction," enables intercellular DNA exchange and further contributes to the spread of antibiotic resistance. Additionally, mobile genetic elements such as transposons, insertion sequences, and site-specific recombination systems like integrons facilitate rearrangement of ARGs, including their translocation between chromosomes and plasmids. This review explores the molecular mechanisms underlying the HGT of ARGs, with a particular focus on clinically isolated antibiotic-resistant Gram-negative bacteria.202540370256
860520.9990Exposure to bisphenol compounds accelerates the conjugative transfer of antibiotic resistance plasmid. Antimicrobial resistance poses the most formidable challenge to public health, with plasmid-mediated horizontal gene transfer playing a pivotal role in its global spread. Bisphenol compounds (BPs), a group of environmental contaminants with endocrine-disrupting properties, are extensively used in various plastic products and can be transmitted to food. However, the impact of BPs on the plasmid-mediated horizontal transfer of antibiotic resistance genes (ARGs) has not yet been elucidated. Herein, we demonstrate that BPs could promote the conjugative transfer frequency of RP4-7 and clinically multidrug-resistant plasmids. Furthermore, the promoting effect of BPs on the plasmid transfer was also confirmed in a murine model. Microbial diversity analysis of transconjugants indicated an increase in α diversity in the BPAF-treated group, along with the declined richness of some beneficial bacteria and elevated richness of Faecalibaculum rodentium, which might serve as an intermediate repository for resistance plasmids. The underlying mechanisms driving the enhanced conjugative transfer upon BPAF treatment include exacerbated oxidative stress, disrupted membrane homeostasis, augmented energy metabolism, and the increased expression of conjugation-related genes. Collectively, our findings highlight the potential risk associated with the exacerbated dissemination of AMR both in vitro and in vivo caused by BPs exposure.202439278585
401130.9990Horizontal Gene Transfer of Antibiotic Resistance Genes in Biofilms. Most bacteria attach to biotic or abiotic surfaces and are embedded in a complex matrix which is known as biofilm. Biofilm formation is especially worrisome in clinical settings as it hinders the treatment of infections with antibiotics due to the facilitated acquisition of antibiotic resistance genes (ARGs). Environmental settings are now considered as pivotal for driving biofilm formation, biofilm-mediated antibiotic resistance development and dissemination. Several studies have demonstrated that environmental biofilms can be hotspots for the dissemination of ARGs. These genes can be encoded on mobile genetic elements (MGEs) such as conjugative and mobilizable plasmids or integrative and conjugative elements (ICEs). ARGs can be rapidly transferred through horizontal gene transfer (HGT) which has been shown to occur more frequently in biofilms than in planktonic cultures. Biofilm models are promising tools to mimic natural biofilms to study the dissemination of ARGs via HGT. This review summarizes the state-of-the-art of biofilm studies and the techniques that visualize the three main HGT mechanisms in biofilms: transformation, transduction, and conjugation.202336830238
677840.9990Bisphenol S Promotes the Transfer of Antibiotic Resistance Genes via Transformation. The antibiotic resistance crisis has seriously jeopardized public health and human safety. As one of the ways of horizontal transfer, transformation enables bacteria to acquire exogenous genes naturally. Bisphenol compounds are now widely used in plastics, food, and beverage packaging, and have become a new environmental pollutant. However, their potential relationship with the spread of antibiotic resistance genes (ARGs) in the environment remains largely unexplored. In this study, we aimed to assess whether the ubiquitous bisphenol S (BPS) could promote the transformation of plasmid-borne ARGs. Using plasmid pUC19 carrying the ampicillin resistance gene as an extracellular ARG and model microorganism E. coli DH5α as the recipient, we established a transformation system. Transformation assays revealed that environmentally relevant concentrations of BPS (0.1-10 μg/mL) markedly enhanced the transformation frequency of plasmid-borne ARGs into E. coli DH5α up to 2.02-fold. Fluorescent probes and transcript-level analyses suggest that BPS stimulated increased reactive oxygen species (ROS) production, activated the SOS response, induced membrane damage, and increased membrane fluidity, which weakened the barrier for plasmid transfer, allowing foreign DNA to be more easily absorbed. Moreover, BPS stimulates ATP supply by activating the tricarboxylic acid (TCA) cycle, which promotes flagellar motility and expands the search for foreign DNA. Overall, these findings provide important insight into the role of bisphenol compounds in facilitating the horizontal spread of ARGs and emphasize the need to monitor the residues of these environmental contaminants.202439337307
860350.9990Ketoprofen promotes the conjugative transfer of antibiotic resistance among antibiotic resistant bacteria in natural aqueous environments. The emergence and spread of antibiotic resistance in the environment pose a serious threat to global public health. It is acknowledged that non-antibiotic stresses, including disinfectants, pharmaceuticals and organic pollutants, play a crucial role in horizontal transmission of antibiotic resistance genes (ARGs). Despite the widespread presence of non-steroidal anti-inflammatory drugs (NSAIDs), notably in surface water, their contributions to the transfer of ARGs have not been systematically explored. Furthermore, previous studies have primarily concentrated on model strains to investigate whether contaminants promote the conjugative transfer of ARGs, leaving the mechanisms of ARG transmission among antibiotic resistant bacteria in natural aqueous environments under the selective pressures of non-antibiotic contaminants remains unclear. In this study, the Escherichia coli (E. coli) K12 carrying RP4 plasmid was used as the donor strain, indigenous strain Aeromonas veronii containing rifampicin resistance genes in Taihu Lake, and E. coli HB101 were used as receptor strains to establish inter-genus and intra-genus conjugative transfer systems, examining the conjugative transfer frequency under the stress of ketoprofen. The results indicated that ketoprofen accelerated the environmental spread of ARGs through several mechanisms. Ketoprofen promoted cell-to-cell contact by increasing cell surface hydrophobicity and reducing cell surface charge, thereby mitigating cell-to-cell repulsion. Furthermore, ketoprofen induced increased levels of reactive oxygen species (ROS) production, activated the DNA damage-induced response (SOS), and enhanced cell membrane permeability, facilitating ARG transmission in intra-genus and inter-genus systems. The upregulation of outer membrane proteins, oxidative stress, SOS response, mating pair formation (Mpf) system, and DNA transfer and replication (Dtr) system related genes, as well as the inhibition of global regulatory genes, all contributed to higher transfer efficiency under ketoprofen treatment. These findings served as an early warning for a comprehensive assessment of the roles of NSAIDs in the spread of antibiotic resistance in natural aqueous environments.202439103039
860460.9990Reactive chlorine species inhibiting interspecies spread of antibiotic resistance via disrupting donor - Recipient cells and regulating plasmid conjugation genes. Current drinking water treatment plant (DWTP) disinfection technologies face limitations, allowing plasmid-mediated antibiotic resistance genes (ARGs) transfer to occur among viable but nonculturable (VBNC) bacteria, heightening the risk of antibiotic-resistant infections. While UV/Chlorine has been adopted to curb ARGs abundance, its impacts on the interspecies transfer of ARG-carrying plasmids remain hardly explored. This study investigated how reactive chlorine species (RCS) in the UV/Chlorine system inhibited the transfer of antibiotic resistance from antibiotic-resistant Escherichia coli (AR E. coli) to Bacillus subtilis (B.S) by inactivating both donor and recipient strains and regulating plasmid conjugation genes. RCS reduced plasmid transfer frequencies by 2.1-log and 3.2-log compared to UV or chlorine alone. By impairing (•)OH scavenging ability, it led to ROS accumulation in AR E. coli, disrupting cellular energy metabolism and DNA repair, ultimately causing DNA degradation and membrane damage, resulting in AR E. coli inactivation rather than entering the VBNC state. Additionally, RCS induced structural and intracellular disruption in B.S, compromising its capacity for plasmid uptake and stable maintenance. Finally, RCS inhibited plasmid horizontal transfer while enhancing vertical transfer, with its damage to outer membrane proteins further restricting interspecies plasmid conjugation transfer. This study provides novel insights for DWTPs to better control ARGs interspecies transfer and improve drinking water safety.202540505407
860270.9989Beta-blocker drives the conjugative transfer of multidrug resistance genes in pure and complex biological systems. Drug resistance poses a high risk to human health. Extensive use of non-antibiotic drugs contributes to antibiotic resistance genes (ARGs) transfer. However, how they affect the spread of broad-host plasmids in complex biological systems remains unknown. This study investigated the effect of metoprolol on the transfer frequency and host range of ARGs in both intrageneric and intergeneric pure culture systems, as well as in anammox microbiome. The results showed that environmental concentrations of metoprolol significantly promoted the intrageneric and intergeneric conjugative transfer. Initially, metoprolol induced excessive oxidative stress, resulting in high cell membrane permeability and bacterial SOS response. Meanwhile, more pili formation increased the adhesion and contact between bacteria, and the abundance of conjugation-related genes also increased significantly. Activation of the electron transport chain provided more ATP for this energy-consuming process. The underlying mechanism was further verified in the complex anammox conjugative system. Metoprolol induced the enrichment of ARGs and mobile genetic elements. The enhanced bacterial interaction and energy generation facilitated the high conjugative transfer frequency of ARGs. In addition, plasmid-borne ARGs tended to transfer to opportunistic pathogens. This work raises public concerns about the health and ecological risks of non-antibiotic drugs.202439096644
924580.9989Type IV Coupling Proteins as Potential Targets to Control the Dissemination of Antibiotic Resistance. The increase of infections caused by multidrug-resistant bacteria, together with the loss of effectiveness of currently available antibiotics, represents one of the most serious threats to public health worldwide. The loss of human lives and the economic costs associated to the problem of the dissemination of antibiotic resistance require immediate action. Bacteria, known by their great genetic plasticity, are capable not only of mutating their genes to adapt to disturbances and environmental changes but also of acquiring new genes that allow them to survive in hostile environments, such as in the presence of antibiotics. One of the major mechanisms responsible for the horizontal acquisition of new genes (e.g., antibiotic resistance genes) is bacterial conjugation, a process mediated by mobile genetic elements such as conjugative plasmids and integrative conjugative elements. Conjugative plasmids harboring antibiotic resistance genes can be transferred from a donor to a recipient bacterium in a process that requires physical contact. After conjugation, the recipient bacterium not only harbors the antibiotic resistance genes but it can also transfer the acquired plasmid to other bacteria, thus contributing to the spread of antibiotic resistance. Conjugative plasmids have genes that encode all the proteins necessary for the conjugation to take place, such as the type IV coupling proteins (T4CPs) present in all conjugative plasmids. Type VI coupling proteins constitute a heterogeneous family of hexameric ATPases that use energy from the ATP hydrolysis for plasmid transfer. Taking into account their essential role in bacterial conjugation, T4CPs are attractive targets for the inhibition of bacterial conjugation and, concomitantly, the limitation of antibiotic resistance dissemination. This review aims to compile present knowledge on T4CPs as a starting point for delving into their molecular structure and functioning in future studies. Likewise, the scientific literature on bacterial conjugation inhibitors has been reviewed here, in an attempt to elucidate the possibility of designing T4CP-inhibitors as a potential solution to the dissemination of multidrug-resistant bacteria.202032903459
401790.9989Non-antibiotic compounds associated with humans and the environment can promote horizontal transfer of antimicrobial resistance genes. Horizontal gene transfer plays a key role in the global dissemination of antimicrobial resistance (AMR). AMR genes are often carried on self-transmissible plasmids, which are shared amongst bacteria primarily by conjugation. Antibiotic use has been a well-established driver of the emergence and spread of AMR. However, the impact of commonly used non-antibiotic compounds and environmental pollutants on AMR spread has been largely overlooked. Recent studies found common prescription and over-the-counter drugs, artificial sweeteners, food preservatives, and environmental pollutants, can increase the conjugative transfer of AMR plasmids. The potential mechanisms by which these compounds promote plasmid transmission include increased membrane permeability, upregulation of plasmid transfer genes, formation of reactive oxygen species, and SOS response gene induction. Many questions remain around the impact of most non-antibiotic compounds on AMR plasmid conjugation in clinical isolates and the long-term impact on AMR dissemination. By elucidating the role of routinely used pharmaceuticals, food additives, and pollutants in the dissemination of AMR, action can be taken to mitigate their impact by closely monitoring use and disposal. This review will discuss recent progress on understanding the influence of non-antibiotic compounds on plasmid transmission, the mechanisms by which they promote transfer, and the level of risk they pose.202437462915
4012100.9989Augmented dissemination of antibiotic resistance elicited by non-antibiotic factors. The emergence and rapid spread of antibiotic resistance seriously compromise the clinical efficacy of current antibiotic therapies, representing a serious public health threat worldwide. Generally, drug-susceptible bacteria can acquire antibiotic resistance through genetic mutation or gene transfer, among which horizontal gene transfer (HGT) plays a dominant role. It is widely acknowledged that the sub-inhibitory concentrations of antibiotics are the key drivers in promoting the transmission of antibiotic resistance. However, accumulating evidence in recent years has shown that in addition to antibiotics, non-antibiotics can also accelerate the horizontal transfer of antibiotic resistance genes (ARGs). Nevertheless, the roles and potential mechanisms of non-antibiotic factors in the transmission of ARGs remain largely underestimated. In this review, we depict the four pathways of HGT and their differences, including conjugation, transformation, transduction and vesiduction. We summarize non-antibiotic factors accounting for the enhanced horizontal transfer of ARGs and their underlying molecular mechanisms. Finally, we discuss the limitations and implications of current studies.202337327521
6771110.9989Triclosan at environmental concentrations can enhance the spread of extracellular antibiotic resistance genes through transformation. The dissemination of antibiotic resistance mediated by horizontal transfer of antibiotic resistance genes (ARGs) is exacerbating the global antibiotic crisis. Currently, little is known about whether non-antibiotic, anti-microbial (NAAM) chemicals are associated with the dissemination of ARGs in the environment. In this study, we aimed to evaluate whether a ubiquitous NAAM chemical, triclosan (TCS), is able to promote the transformation of plasmid-borne antibiotic resistance genes (ARGs). By using the plasmid pUC19 carrying ampicillin resistance genes as the extracellular ARG and a model microorganism Escherichia coli DH5ɑ as the recipient, we found that TCS at environmentally detected concentrations (0.2 μg/L to 20 μg/L) significantly enhanced the transformation of plasmid-borne ARGs into E. coli DH5ɑ for up to 1.4-fold. The combination of phenotypic experiments, genome-wide RNA sequencing and proteomic analyses revealed that TCS exposure stimulated the reactive oxygen species (ROS) production for 1.3- to 1.5-fold, induced bacterial membrane damage and up-regulated the translation of outer membrane porin. Moreover, general secretion system Sec (1.4-fold), twin arginine translocation system Tat (1.2-fold) and type IV pilus secretion systems (2.5-fold) were enhanced by TCS, which might contribute to the DNA searching/capture by pilus. Together, TCS might increase the transformation frequency of ARGs into E. coli DH5ɑ by ROS over-production, damaging cell membrane barrier, mediating the pilus capture of plasmid and the translocation of plasmid via cell membrane channels. This study reports that TCS could accelerate the transformation of extracellular ARGs to competent bacteria at environmentally relevant concentrations. The findings advance our understanding of the fate of ARGs in ecosystems and call for risk assessments of NAAM chemicals on disseminating antibiotic resistance.202032019018
4006120.9989Targeting 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
9934130.9989Planktonic and Biofilm-Derived Pseudomonas aeruginosa Outer Membrane Vesicles Facilitate Horizontal Gene Transfer of Plasmid DNA. Outer membrane vesicles (OMVs) produced by Gram-negative bacteria package various cargo, including DNA that can be transferred to other bacteria or to host cells. OMV-associated DNA has been implicated in mediating horizontal gene transfer (HGT) between bacteria, which includes the dissemination of antibiotic resistance genes within and between bacterial species. Despite the known ability of OMVs to mediate HGT, the mechanisms of DNA packaging into OMVs remain poorly characterized, as does the effect of bacterial growth conditions on the DNA cargo composition of OMVs and their subsequent abilities to mediate HGT. In this study, we examined the DNA content of OMVs produced by the opportunistic pathogen Pseudomonas aeruginosa grown in either planktonic or biofilm conditions. Analysis of planktonic growth-derived OMVs revealed their ability to package and protect plasmid DNA from DNase degradation and to transfer plasmid-encoded antibiotic resistance genes to recipient, antibiotic-sensitive P. aeruginosa bacteria at a greater efficiency than transformation with plasmid alone. Comparisons of planktonic and biofilm-derived P. aeruginosa OMVs demonstrated that biofilm-derived OMVs were smaller but were associated with more plasmid DNA than planktonic-derived OMVs. Additionally, biofilm-derived P. aeruginosa OMVs were more efficient in the transformation of competent P. aeruginosa bacteria, compared to transformations with an equivalent number of planktonic-derived OMVs. The findings of this study highlight the importance of bacterial growth conditions for the packaging of DNA within P. aeruginosa OMVs and their ability to facilitate HGT, thus contributing to the spread of antibiotic resistance genes between P. aeruginosa bacteria. IMPORTANCE Bacterial membrane vesicles (BMVs) mediate interbacterial communication, and their ability to package DNA specifically contributes to biofilm formation, antibiotic resistance, and HGT between bacteria. However, the ability of P. aeruginosa OMVs to mediate HGT has not yet been demonstrated. Here, we reveal that P. aeruginosa planktonic and biofilm-derived OMVs can deliver plasmid-encoded antibiotic resistance to recipient P. aeruginosa. Additionally, we demonstrated that P. aeruginosa biofilm-derived OMVs were associated with more plasmid DNA compared to planktonic-derived OMVs and were more efficient in the transfer of plasmid DNA to recipient bacteria. Overall, this demonstrated the ability of P. aeruginosa OMVs to facilitate the dissemination of antibiotic resistance genes, thereby enabling the survival of susceptible bacteria during antibiotic treatment. Investigating the roles of biofilm-derived BMVs may contribute to furthering our understanding of the role of BMVs in HGT and the spread of antibiotic resistance in the environment.202336946779
3780140.9989Is 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
9264150.9989Nanoalumina promotes the horizontal transfer of multiresistance genes mediated by plasmids across genera. Antibiotic resistance is a worldwide public health concern. Conjugative transfer between closely related strains or species of bacteria is an important method for the horizontal transfer of multidrug-resistance genes. The extent to which nanomaterials are able to cause an increase in antibiotic resistance by the regulation of the conjugative transfer of antibiotic-resistance genes in bacteria, especially across genera, is still unknown. Here we show that nanomaterials in water can significantly promote the horizontal conjugative transfer of multidrug-resistance genes mediated by the RP4, RK2, and pCF10 plasmids. Nanoalumina can promote the conjugative transfer of the RP4 plasmid from Escherichia coli to Salmonella spp. by up to 200-fold compared with untreated cells. We also explored the mechanisms behind this phenomenon and demonstrate that nanoalumina is able to induce oxidative stress, damage bacterial cell membranes, enhance the expression of mating pair formation genes and DNA transfer and replication genes, and depress the expression of global regulatory genes that regulate the conjugative transfer of RP4. These findings are important in assessing the risk of nanomaterials to the environment, particularly from water and wastewater treatment systems, and in the estimation of the effect of manufacture and use of nanomaterials on the environment.201222411796
6776160.9989Natural sphalerite nanoparticles can accelerate horizontal transfer of plasmid-mediated antibiotic-resistance genes. Minerals and microorganisms are integral parts of natural environments, and they inevitably interact. Antibiotic-resistance genes (ARGs) significantly threaten modern healthcare. However, the effects of natural minerals on ARG propagation in aquatic systems are not fully understood. The present work studied the effects of natural sphalerite (NS) nanoparticles on the horizontal transfer of ARGs from Escherichia coli DH5α (CTX) (donor) to E. coli C600 (Sm) (recipient), and from E. coli DH5α (MCR) (donor) to E. coli C600 (Sm), and their underlying mechanisms. NS particles (0.5-50 mg L(-1)) induced an NS-concentration-dependent increase in conjugative transfer frequency. The underlying mechanisms associated with the facilitated ARG transfer included the production of intracellular reactive oxygen species, the SOS response, changes in bacterial cell morphology, and alteration of mRNA levels of bacterial cell membrane protein-related genes and genes associated with conjugative ARG transfer. The information herein offers new mechanistic understanding of risks of bacterial resistance resulting from NS.202031999971
6770170.9989Triclosan at environmentally relevant concentrations promotes horizontal transfer of multidrug resistance genes within and across bacterial genera. BACKGROUND: Antibiotic resistance poses an increasing threat to public health. Horizontal gene transfer (HGT) promoted by antibiotics is recognized as a significant pathway to disseminate antibiotic resistance genes (ARGs). However, it is unclear whether non-antibiotic, anti-microbial (NAAM) chemicals can directly promote HGT of ARGs in the environment. OBJECTIVES: We aimed to investigate whether triclosan (TCS), a widely-used NAAM chemical in personal care products, is able to stimulate the conjugative transfer of antibiotic multi-resistance genes carried by plasmid within and across bacterial genera. METHODS: We established two model mating systems, to investigate intra-genera transfer and inter-genera transfer. Escherichia coli K-12 LE392 carrying IncP-α plasmid RP4 was used as the donor, and E. coli K-12 MG1655 or Pseudomonas putida KT2440 were the intra- and inter-genera recipients, respectively. The mechanisms of the HGT promoted by TCS were unveiled by detecting oxidative stress and cell membrane permeability, in combination with Nanopore sequencing, genome-wide RNA sequencing and proteomic analyses. RESULTS: Exposure of the bacteria to environmentally relevant concentrations of TCS (from 0.02 μg/L to 20 μg/L) significantly stimulated the conjugative transfer of plasmid-encoded multi-resistance genes within and across genera. The TCS exposure promoted ROS generation and damaged bacterial membrane, and caused increased expression of the SOS response regulatory genes umuC, dinB and dinD in the donor. In addition, higher expression levels of ATP synthesis encoding genes in E. coli and P. putida were found with increased TCS dosage. CONCLUSIONS: TCS could enhance the conjugative ARGs transfer between bacteria by triggering ROS overproduction at environmentally relevant concentrations. These findings improve our awareness of the hidden risks of NAAM chemicals on the spread of antibiotic resistance.201830389380
4013180.9989Correlation 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
9260190.9989The Evolution of Plasmid Transfer Rate in Bacteria and Its Effect on Plasmid Persistence. AbstractPlasmids are extrachromosomal segments of DNA that can transfer genes between bacterial cells. Many plasmid genes benefit bacteria but cause harm to human health by granting antibiotic resistance to pathogens. Transfer rate is a key parameter for predicting plasmid dynamics, but observed rates are highly variable, and the effects of selective forces on their evolution are unclear. We apply evolutionary analysis to plasmid conjugation models to investigate selective pressures affecting plasmid transfer rate, emphasizing host versus plasmid control, the costs of plasmid transfer, and the role of recipient cells. Our analyses show that plasmid-determined transfer rates can be predicted with three parameters (host growth rate, plasmid loss rate, and the cost of plasmid transfer on growth) under some conditions. We also show that low-frequency genetic variation in transfer rate can accumulate, facilitating rapid adaptation to changing conditions. Furthermore, reduced transfer rates due to host control have limited effects on plasmid prevalence until low enough to prevent plasmid persistence. These results provide a framework to predict plasmid transfer rate evolution in different environments and demonstrate the limited impact of host mechanisms to control the costs incurred when plasmids are present.202134559608