Interaction with a phage gene underlie costs of a β-lactamase. - Related Documents




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382801.0000Interaction with a phage gene underlie costs of a β-lactamase. The fitness cost of an antibiotic resistance gene (ARG) can differ across host strains, creating refuges that allow the maintenance of an ARG in the absence of direct selection for its resistance phenotype. Despite the importance of such ARG-host interactions for predicting ARG dynamics, the basis of ARG fitness costs and their variability between hosts are not well understood. We determined the genetic basis of a host-dependent cost of a β-lactamase, bla(TEM-116*), that conferred a significant cost in one Escherichia coli strain but was close to neutral in 11 other Escherichia spp. strains. Selection of a bla(TEM-116*)-encoding plasmid in the strain in which it initially had a high cost resulted in rapid and parallel compensation for that cost through mutations in a P1-like phage gene, relA(P1). When the wild-type relA(P1) gene was added to a strain in which it was not present and in which bla(TEM-116*) was neutral, it caused the ARG to become costly. Thus, relA(P1) is both necessary and sufficient to explain bla(TEM-116*) costs in at least some host backgrounds. To our knowledge, these findings represent the first demonstrated case of the cost of an ARG being influenced by a genetic interaction with a phage gene. The interaction between a phage gene and a plasmid-borne ARG highlights the complexity of selective forces determining the maintenance and spread of ARGs and, by extension, encoding phage and plasmids in natural bacterial communities.IMPORTANCEAntibiotic resistance genes (ARGs) play a major role in the increasing problem of antibiotic resistance in clinically relevant bacteria. Selection of these genes occurs in the presence of antibiotics, but their eventual success also depends on the sometimes substantial costs they impose on host bacteria in antibiotic-free environments. We evolved an ARG that confers resistance to penicillin-type antibiotics in one host in which it did confer a cost and in one host in which it did not. We found that costs were rapidly and consistently reduced through parallel genetic changes in a gene encoded by a phage that was infecting the costly host. The unmutated version of this gene was sufficient to cause the ARG to confer a cost in a host in which it was originally neutral, demonstrating an antagonism between the two genetic elements and underlining the range and complexity of pressures determining ARG dynamics in natural populations.202438194254
383010.9999Resistance Gene Carriage Predicts Growth of Natural and Clinical Escherichia coli Isolates in the Absence of Antibiotics. Bacterial pathogens that carry antibiotic resistance alleles sometimes pay a cost in the form of impaired growth in antibiotic-free conditions. This cost of resistance is expected to be a key parameter for understanding how resistance spreads and persists in pathogen populations. Analysis of individual resistance alleles from laboratory evolution and natural isolates has shown they are typically costly, but these costs are highly variable and influenced by genetic variation at other loci. It therefore remains unclear how strongly resistance is linked to impaired antibiotic-free growth in bacteria from natural and clinical scenarios, where resistance alleles are likely to coincide with other types of genetic variation. To investigate this, we measured the growth of 92 natural and clinical Escherichia coli isolates across three antibiotic-free environments. We then tested whether variation of antibiotic-free growth among isolates was predicted by their resistance to 10 antibiotics, while accounting for the phylogenetic structure of the data. We found that isolates with similar resistance profiles had similar antibiotic-free growth profiles, but it was not simply that higher average resistance was associated with impaired growth. Next, we used whole-genome sequences to identify antibiotic resistance genes and found that isolates carrying a greater number of resistance gene types grew relatively poorly in antibiotic-free conditions, even when the resistance genes they carried were different. This suggests that the resistance of bacterial pathogens is linked to growth costs in nature, but it is the total genetic burden and multivariate resistance phenotype that predict these costs, rather than individual alleles or mean resistance across antibiotics.IMPORTANCE Managing the spread of antibiotic resistance in bacterial pathogens is a major challenge for global public health. Central to this challenge is understanding whether resistance is linked to impaired bacterial growth in the absence of antibiotics, because this determines whether resistance declines when bacteria are no longer exposed to antibiotics. We studied 92 isolates of the key bacterial pathogen Escherichia coli; these isolates varied in both their antibiotic resistance genes and other parts of the genome. Taking this approach, rather than focusing on individual genetic changes associated with resistance as in much previous work, revealed that growth without antibiotics was linked to the number of specialized resistance genes carried and the combination of antibiotics to which isolates were resistant but was not linked to average antibiotic resistance. This approach provides new insights into the genetic factors driving the long-term persistence of antibiotic-resistant bacteria, which is important for future efforts to predict and manage resistance.201930530714
382720.9999The fitness cost of horizontally transferred and mutational antimicrobial resistance in Escherichia coli. Antimicrobial resistance (AMR) in bacteria implies a tradeoff between the benefit of resistance under antimicrobial selection pressure and the incurred fitness cost in the absence of antimicrobials. The fitness cost of a resistance determinant is expected to depend on its genetic support, such as a chromosomal mutation or a plasmid acquisition, and on its impact on cell metabolism, such as an alteration in an essential metabolic pathway or the production of a new enzyme. To provide a global picture of the factors that influence AMR fitness cost, we conducted a systematic review and meta-analysis focused on a single species, Escherichia coli. By combining results from 46 high-quality studies in a multilevel meta-analysis framework, we find that the fitness cost of AMR is smaller when provided by horizontally transferable genes such as those encoding beta-lactamases, compared to mutations in core genes such as those involved in fluoroquinolone and rifampicin resistance. We observe that the accumulation of acquired AMR genes imposes a much smaller burden on the host cell than the accumulation of AMR mutations, and we provide quantitative estimates of the additional cost of a new gene or mutation. These findings highlight that gene acquisition is more efficient than the accumulation of mutations to evolve multidrug resistance, which can contribute to the observed dominance of horizontally transferred genes in the current AMR epidemic.202337455716
382630.9999Co-resistance: an opportunity for the bacteria and resistance genes. Co-resistance involves transfer of several genes into the same bacteria and/or the acquisition of mutations in different genetic loci affecting different antimicrobials whereas pleiotropic resistance implies the same genetic event affecting several antimicrobials. There is an increasing prevalence of isolates with co-resistance which are over-represented within the so-called high-risk clones. Compensatory events avoid fitness cost of co-resistance, even in the absence of antimicrobials. Nevertheless, they might be selected by different antimicrobials and a single agent might select co-resistant isolates. This process, named as co-selection, is not avoided with cycling or mixing strategies of antimicrobial use. Co-resistance and co-selection processes increase the opportunity for persistence of the bacteria and resistance genes and should be considered when designing strategies for decreasing antimicrobial resistance.201121840259
379640.9999The presence of plasmids in bacterial hosts alters phage isolation and infectivity. Antibiotic resistance genes are often carried by plasmids, which spread intra- and inter genera bacterial populations, and also play a critical role in bacteria conferring phage resistance. However, it remains unknown about the influence of plasmids present in bacterial hosts on phage isolation and subsequent infectivity. In this study, using both Escherichia coli and Pseudomonas putida bacteria containing different plasmids, eight phages were isolated and characterized in terms of phage morphology and host range analysis, in conjunction with DNA and protein sequencing. We found that plasmids can influence both the phage isolation process and phage infectivity. In particular, the isolated phages exhibited different phage plaquing infectivity towards the same bacterial species containing different plasmids. Furthermore, the presence of plasmids was found to alter the expression of bacteria membrane protein, which correlates with bacterial cell surface receptors recognized by phages, thus affecting phage isolation and infectivity. Given the diverse and ubiquitous nature of plasmids, our findings highlight the need to consider plasmids as factors that can influence both phage isolation and infectivity.202237938681
381150.9999Minor fitness costs in an experimental model of horizontal gene transfer in bacteria. Genes introduced by horizontal gene transfer (HGT) from other species constitute a significant portion of many bacterial genomes, and the evolutionary dynamics of HGTs are important for understanding the spread of antibiotic resistance and the emergence of new pathogenic strains of bacteria. The fitness effects of the transferred genes largely determine the fixation rates and the amount of neutral diversity of newly acquired genes in bacterial populations. Comparative analysis of bacterial genomes provides insight into what genes are commonly transferred, but direct experimental tests of the fitness constraints on HGT are scarce. Here, we address this paucity of experimental studies by introducing 98 random DNA fragments varying in size from 0.45 to 5 kb from Bacteroides, Proteus, and human intestinal phage into a defined position in the Salmonella chromosome and measuring the effects on fitness. Using highly sensitive competition assays, we found that eight inserts were deleterious with selection coefficients (s) ranging from ≈ -0.007 to -0.02 and 90 did not have significant fitness effects. When inducing transcription from a PBAD promoter located at one end of the insert, 16 transfers were deleterious and 82 were not significantly different from the control. In conclusion, a major fraction of the inserts had minor effects on fitness implying that extra DNA transferred by HGT, even though it does not confer an immediate selective advantage, could be maintained at selection-transfer balance and serve as raw material for the evolution of novel beneficial functions.201424536043
965560.9999High genomic diversity of multi-drug resistant wastewater Escherichia coli. Wastewater treatment plants play an important role in the emergence of antibiotic resistance. They provide a hot spot for exchange of resistance within and between species. Here, we analyse and quantify the genomic diversity of the indicator Escherichia coli in a German wastewater treatment plant and we relate it to isolates' antibiotic resistance. Our results show a surprisingly large pan-genome, which mirrors how rich an environment a treatment plant is. We link the genomic analysis to a phenotypic resistance screen and pinpoint genomic hot spots, which correlate with a resistance phenotype. Besides well-known resistance genes, this forward genomics approach generates many novel genes, which correlated with resistance and which are partly completely unknown. A surprising overall finding of our analyses is that we do not see any difference in resistance and pan genome size between isolates taken from the inflow of the treatment plant and from the outflow. This means that while treatment plants reduce the amount of bacteria released into the environment, they do not reduce the potential for antibiotic resistance of these bacteria.201829895899
383270.9999A population genomics approach to exploiting the accessory 'resistome' of Escherichia coli. The emergence of antibiotic resistance is a defining challenge, and Escherichia coli is recognized as one of the leading species resistant to the antimicrobials used in human or veterinary medicine. Here, we analyse the distribution of 2172 antimicrobial-resistance (AMR) genes in 4022 E. coli to provide a population-level view of resistance in this species. By separating the resistance determinants into 'core' (those found in all strains) and 'accessory' (those variably present) determinants, we have found that, surprisingly, almost half of all E. coli do not encode any accessory resistance determinants. However, those strains that do encode accessory resistance are significantly more likely to be resistant to multiple antibiotic classes than would be expected by chance. Furthermore, by studying the available date of isolation for the E. coli genomes, we have visualized an expanding, highly interconnected network that describes how resistances to antimicrobials have co-associated within genomes over time. These data can be exploited to reveal antimicrobial combinations that are less likely to be found together, and so if used in combination may present an increased chance of suppressing the growth of bacteria and reduce the rate at which resistance factors are spread. Our study provides a complex picture of AMR in the E. coli population. Although the incidence of resistance to all studied antibiotic classes has increased dramatically over time, there exist combinations of antibiotics that could, in theory, attack the entirety of E. coli, effectively removing the possibility that discrete AMR genes will increase in frequency in the population.201728785420
382980.9999Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical Escherichia coli Isolates. The spread of antibiotic resistance is driving interest in new approaches to control bacterial pathogens. This includes applying multiple antibiotics strategically, using bacteriophages against antibiotic-resistant bacteria, and combining both types of antibacterial agents. All these approaches rely on or are impacted by associations among resistance phenotypes (where bacteria resistant to one antibacterial agent are also relatively susceptible or resistant to others). Experiments with laboratory strains have shown strong associations between some resistance phenotypes, but we lack a quantitative understanding of associations among antibiotic and phage resistance phenotypes in natural and clinical populations. To address this, we measured resistance to various antibiotics and bacteriophages for 94 natural and clinical Escherichia coli isolates. We found several positive associations between resistance phenotypes across isolates. Associations were on average stronger for antibacterial agents of the same type (antibiotic-antibiotic or phage-phage) than different types (antibiotic-phage). Plasmid profiles and genetic knockouts suggested that such associations can result from both colocalization of resistance genes and pleiotropic effects of individual resistance mechanisms, including one case of antibiotic-phage cross-resistance. Antibiotic resistance was predicted by core genome phylogeny and plasmid profile, but phage resistance was predicted only by core genome phylogeny. Finally, we used observed associations to predict genes involved in a previously uncharacterized phage resistance mechanism, which we verified using experimental evolution. Our data suggest that susceptibility to phages and antibiotics are evolving largely independently, and unlike in experiments with lab strains, negative associations between antibiotic resistance phenotypes in nature are rare. This is relevant for treatment scenarios where bacteria encounter multiple antibacterial agents.IMPORTANCE Rising antibiotic resistance is making it harder to treat bacterial infections. Whether resistance to a given antibiotic spreads or declines is influenced by whether it is associated with altered susceptibility to other antibiotics or other stressors that bacteria encounter in nature, such as bacteriophages (viruses that infect bacteria). We used natural and clinical isolates of Escherichia coli, an abundant species and key pathogen, to characterize associations among resistance phenotypes to various antibiotics and bacteriophages. We found associations between some resistance phenotypes, and in contrast to past work with laboratory strains, they were exclusively positive. Analysis of bacterial genome sequences and horizontally transferred genetic elements (plasmids) helped to explain this, as well as our finding that there was no overall association between antibiotic resistance and bacteriophage resistance profiles across isolates. This improves our understanding of resistance evolution in nature, potentially informing new rational therapies that combine different antibacterials, including bacteriophages.201729089428
383190.9999The distribution of fitness effects of plasmid pOXA-48 in clinical enterobacteria. Antimicrobial resistance (AMR) in bacteria is a major public health problem. The main route for AMR acquisition in clinically important bacteria is the horizontal transfer of plasmids carrying resistance genes. AMR plasmids allow bacteria to survive antibiotics, but they also entail physiological alterations in the host cell. Multiple studies over the last few years have indicated that these alterations can translate into a fitness cost when antibiotics are absent. However, due to technical limitations, most of these studies are based on analysing new associations between plasmids and bacteria generated in vitro, and we know very little about the effects of plasmids in their native bacterial hosts. In this study, we used a CRISPR-Cas9-tool to selectively cure plasmids from clinical enterobacteria to overcome this limitation. Using this approach, we were able to study the fitness effects of the carbapenem resistance plasmid pOXA-48 in 35 pOXA-48-carrying isolates recovered from hospitalized patients. Our results revealed that pOXA-48 produces variable effects across the collection of wild-type enterobacterial strains naturally carrying the plasmid, ranging from fitness costs to fitness benefits. Importantly, the plasmid was only associated with a significant fitness reduction in four out of 35 clones, and produced no significant changes in fitness in the great majority of isolates. Our results suggest that plasmids produce neutral fitness effects in most native bacterial hosts, helping to explain the great prevalence of plasmids in natural microbial communities.202337505800
3836100.9999Bacterial recombination promotes the evolution of multi-drug-resistance in functionally diverse populations. Bacterial recombination is believed to be a major factor explaining the prevalence of multi-drug-resistance (MDR) among pathogenic bacteria. Despite extensive evidence for exchange of resistance genes from retrospective sequence analyses, experimental evidence for the evolutionary benefits of bacterial recombination is scarce. We compared the evolution of MDR between populations of Acinetobacter baylyi in which we manipulated both the recombination rate and the initial diversity of strains with resistance to single drugs. In populations lacking recombination, the initial presence of multiple strains resistant to different antibiotics inhibits the evolution of MDR. However, in populations with recombination, the inhibitory effect of standing diversity is alleviated and MDR evolves rapidly. Moreover, only the presence of DNA harbouring resistance genes promotes the evolution of resistance, ruling out other proposed benefits for recombination. Together, these results provide direct evidence for the fitness benefits of bacterial recombination and show that this occurs by mitigation of functional interference between genotypes resistant to single antibiotics. Although analogous to previously described mechanisms of clonal interference among alternative beneficial mutations, our results actually highlight a different mechanism by which interactions among co-occurring strains determine the benefits of recombination for bacterial evolution.201222048956
3835110.9999Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria. The rise of antibiotic resistance is a critical public health concern, requiring an understanding of mechanisms that enable bacteria to tolerate antimicrobial agents. Bacteria use diverse strategies, including the amplification of drug-resistance genes. In this paper, we showed that multicopy plasmids, often carrying antibiotic resistance genes in clinical bacteria, can rapidly amplify genes, leading to plasmid-mediated phenotypic noise and transient antibiotic resistance. By combining stochastic simulations of a computational model with high-throughput single-cell measurements of bla(TEM-1) expression in Escherichia coli MG1655, we showed that plasmid copy number variability stably maintains populations composed of cells with both low and high plasmid copy numbers. This diversity in plasmid copy number enhances the probability of bacterial survival in the presence of antibiotics, while also rapidly reducing the burden of carrying multiple plasmids in drug-free environments. Our results further support the tenet that multicopy plasmids not only act as vehicles for the horizontal transfer of genetic information between cells but also as drivers of bacterial adaptation, enabling rapid modulation of gene copy numbers. Understanding the role of multicopy plasmids in antibiotic resistance is critical, and our study provides insights into how bacteria can transiently survive lethal concentrations of antibiotics.202438521779
9629120.9999Costs of antibiotic resistance genes depend on host strain and environment and can influence community composition. Antibiotic resistance genes (ARGs) benefit host bacteria in environments containing corresponding antibiotics, but it is less clear how they are maintained in environments where antibiotic selection is weak or sporadic. In particular, few studies have measured if the direct effect of ARGs on host fitness is fixed or if it depends on the host strain, perhaps marking some ARG-host combinations as selective refuges that can maintain ARGs in the absence of antibiotic selection. We quantified the fitness effects of six ARGs in 11 diverse Escherichia spp. strains. Three ARGs (bla(TEM-116), cat and dfrA5, encoding resistance to β-lactams, chloramphenicol, and trimethoprim, respectively) imposed an overall cost, but all ARGs had an effect in at least one host strain, reflecting a significant strain interaction effect. A simulation predicts these interactions can cause the success of ARGs to depend on available host strains, and, to a lesser extent, can cause host strain success to depend on the ARGs present in a community. These results indicate the importance of considering ARG effects across different host strains, and especially the potential of refuge strains to allow resistance to persist in the absence of direct selection, in efforts to understand resistance dynamics.202438889784
3837130.9999Evolutionary Paths That Expand Plasmid Host-Range: Implications for Spread of Antibiotic Resistance. The World Health Organization has declared the emergence of antibiotic resistance to be a global threat to human health. Broad-host-range plasmids have a key role in causing this health crisis because they transfer multiple resistance genes to a wide range of bacteria. To limit the spread of antibiotic resistance, we need to gain insight into the mechanisms by which the host range of plasmids evolves. Although initially unstable plasmids have been shown to improve their persistence through evolution of the plasmid, the host, or both, the means by which this occurs are poorly understood. Here, we sought to identify the underlying genetic basis of expanded plasmid host-range and increased persistence of an antibiotic resistance plasmid using a combined experimental-modeling approach that included whole-genome resequencing, molecular genetics and a plasmid population dynamics model. In nine of the ten previously evolved clones, changes in host and plasmid each slightly improved plasmid persistence, but their combination resulted in a much larger improvement, which indicated positive epistasis. The only genetic change in the plasmid was the acquisition of a transposable element from a plasmid native to the Pseudomonas host used in these studies. The analysis of genetic deletions showed that the critical genes on this transposon encode a putative toxin-antitoxin (TA) and a cointegrate resolution system. As evolved plasmids were able to persist longer in multiple naïve hosts, acquisition of this transposon also expanded the plasmid's host range, which has important implications for the spread of antibiotic resistance.201626668183
3797140.9999Human intestinal cells modulate conjugational transfer of multidrug resistance plasmids between clinical Escherichia coli isolates. Bacterial conjugation in the human gut microbiota is believed to play a major role in the dissemination of antibiotic resistance genes and virulence plasmids. However, the modulation of bacterial conjugation by the human host remains poorly understood and there is a need for controlled systems to study this process. We established an in vitro co-culture system to study the interaction between human intestinal cells and bacteria. We show that the conjugation efficiency of a plasmid encoding an extended spectrum beta-lactamase is reduced when clinical isolates of Escherichia coli are co-cultured with human intestinal cells. We show that filtered media from co-cultures contain a factor that reduces conjugation efficiency. Protease treatment of the filtered media eliminates this inhibition of conjugation. This data suggests that a peptide or protein based factor is secreted on the apical side of the intestinal cells exposed to bacteria leading to a two-fold reduction in conjugation efficiency. These results show that human gut epithelial cells can modulate bacterial conjugation and may have relevance to gene exchange in the gut.201424955767
4167150.9999Lateral Antimicrobial Resistance Genetic Transfer is active in the open environment. Historically, the environment has been viewed as a passive deposit of antimicrobial resistance mechanisms, where bacteria show biological cost for maintenance of these genes. Thus, in the absence of antimicrobial pressure, it is expected that they disappear from environmental bacterial communities. To test this scenario, we studied native IntI1 functionality of 11 class 1 integron-positive environmental strains of distant genera collected in cold and subtropical forests of Argentina. We found natural competence and successful site-specific insertion with no significant fitness cost of both aadB and bla (VIM-2) antimicrobial resistance gene cassettes, in a model system without antibiotic pressure. A bidirectional flow of antimicrobial resistance gene cassettes between natural and nosocomial habitats is proposed, which implies an active role of the open environment as a reservoir, recipient and source of antimicrobial resistance mechanisms, outlining an environmental threat where novel concepts of rational use of antibiotics are extremely urgent and mandatory.201728364120
3799160.9999Antibiotic Degradation by Commensal Microbes Shields Pathogens. The complex bacterial populations that constitute the gut microbiota can harbor antibiotic resistance genes (ARGs), including those encoding β-lactamase enzymes (BLA), which degrade commonly prescribed antibiotics such as ampicillin. The prevalence of such genes in commensal bacteria has been increased in recent years by the wide use of antibiotics in human populations and in livestock. While transfer of ARGs between bacterial species has well-established dramatic public health implications, these genes can also function in trans within bacterial consortia, where antibiotic-resistant bacteria can provide antibiotic-sensitive neighbors with leaky protection from drugs, as shown both in vitro and in vivo, in models of lung and subcutaneous coinfection. However, whether the expression of ARGs by harmless commensal bacterial species can destroy antibiotics in the intestinal lumen and shield antibiotic-sensitive pathogens is unknown. To address this question, we colonized germfree or wild-type mice with a model intestinal commensal strain of Escherichia coli that produces either functional or defective BLA. Mice were subsequently infected with Listeria monocytogenes or Clostridioides difficile, followed by treatment with oral ampicillin. The production of functional BLA by commensal E. coli markedly reduced clearance of these pathogens and enhanced systemic dissemination during ampicillin treatment. Pathogen resistance was independent of ARG acquisition via horizontal gene transfer but instead relied on antibiotic degradation in the intestinal lumen by BLA. We conclude that commensal bacteria that have acquired ARGs can mediate shielding of pathogens from the bactericidal effects of antibiotics.202031964746
9258170.9999Plasmid Viability Depends on the Ecological Setting of Hosts within a Multiplasmid Community. Plasmids are extrachromosomal genetic elements, some of which disperse horizontally between different strains and species of bacteria. They are a major factor in the dissemination of virulence factors and antibiotic resistance. Understanding the ecology of plasmids has a notable anthropocentric value, and therefore, the interactions between bacterial hosts and individual plasmids have been studied in detail. However, bacterial systems often carry multiple genetically distinct plasmids, but dynamics within these multiplasmid communities have remained unstudied. Here, we set to investigate the survival of 11 mobilizable or conjugative plasmids under five different conditions where the hosts had a differing ecological status in comparison to other bacteria in the system. The key incentive was to determine whether plasmid dynamics are reproducible and whether there are tradeoffs in plasmid fitness that stem from the ecological situation of their initial hosts. Growth rates and maximum population densities increased in all communities and treatments over the 42-day evolution experiment, although plasmid contents at the end varied notably. Large multiresistance-conferring plasmids were unfit when the community also contained smaller plasmids with fewer resistance genes. This suggests that restraining the use of a few antibiotics can make bacterial communities sensitive to others. In general, the presence or absence of antibiotic selection and plasmid-free hosts (of various fitnesses) has a notable influence on which plasmids survive. These tradeoffs in different settings can help explain, for example, why some resistance plasmids have an advantage during a rapid proliferation of antibiotic-sensitive pathogens whereas others dominate in alternative situations. IMPORTANCE Conjugative and mobilizable plasmids are ubiquitous in bacterial systems. Several different plasmids can compete within a single bacterial community. We here show that the ecological setting of the host bacteria has a notable effect on the survival of individual plasmids. Selection for opportunistic genes such as antibiotic resistance genes and the presence of plasmid-free hosts can determine which plasmids survive in the system. Host bacteria appear to adapt specifically to a situation where there are multiple plasmids present instead of alleviating the plasmid-associated fitness costs of individual plasmids. Plasmids providing antibiotic resistance survived under all conditions even if there was a constant migration of higher-fitness plasmid-free hosts and no selection via antibiotics. This study is one of the first to observe the behavior of multiple genetically different plasmids as a part of a single system.202235416702
4169180.9999Impact of Natural Transformation on the Acquisition of Novel Genes in Bacteria. Natural transformation is the only process of gene exchange under the exclusive control of the recipient bacteria. It has often been considered as a source of novel genes, but quantitative assessments of this claim are lacking. To investigate the potential role of natural transformation in gene acquisition, we analyzed a large collection of genomes of Acinetobacter baumannii (Ab) and Legionella pneumophila (Lp) for which transformation rates were experimentally determined. Natural transformation rates are weakly correlated with genome size. But they are negatively associated with gene turnover in both species. This might result from a negative balance between the transformation's ability to cure the chromosome from mobile genetic elements (MGEs), resulting in gene loss, and its facilitation of gene acquisition. By comparing gene gains by transformation and MGEs, we found that transformation was associated with the acquisition of small sets of genes per event, which were also spread more evenly in the chromosome. We estimated the contribution of natural transformation to gene gains by comparing recombination-driven gene acquisition rates between transformable and non-transformable strains, finding that it facilitated the acquisition of ca. 6.4% (Ab) and 1.1% (Lp) of the novel genes. This moderate contribution of natural transformation to gene acquisition implies that most novel genes are acquired by other means. Yet, 15% of the recently acquired antibiotic resistance genes in A. baumannii may have been acquired by transformation. Hence, natural transformation may drive the acquisition of relatively few novel genes, but these may have a high fitness impact.202540794765
9651190.9999Host- plasmid network structure in wastewater is linked to antimicrobial resistance genes. As mobile genetic elements, plasmids are central for our understanding of antimicrobial resistance spread in microbial communities. Plasmids can have varying fitness effects on their host bacteria, which will markedly impact their role as antimicrobial resistance vectors. Using a plasmid population model, we first show that beneficial plasmids interact with a higher number of hosts than costly plasmids when embedded in a community with multiple hosts and plasmids. We then analyse the network of a natural host-plasmid wastewater community from a Hi-C metagenomics dataset. As predicted by the model, we find that antimicrobial resistance encoding plasmids, which are likely to have positive fitness effects on their hosts in wastewater, interact with more bacterial taxa than non-antimicrobial resistance plasmids and are disproportionally important for connecting the entire network compared to non- antimicrobial resistance plasmids. This highlights the role of antimicrobials in restructuring host-plasmid networks by increasing the benefits of antimicrobial resistance carrying plasmids, which can have consequences for the spread of antimicrobial resistance genes through microbial networks. Furthermore, that antimicrobial resistance encoding plasmids are associated with a broader range of hosts implies that they will be more robust to turnover of bacterial strains.202438228585