Survival and evolution of a large multidrug resistance plasmid in new clinical bacterial hosts
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PROVIDER: PRJEB14458 | ENA |
REPOSITORIES: ENA
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Project description:Large conjugative plasmids are important drivers of bacterial evolution and contribute significantly to the dissemination of antibiotic resistance. Although plasmid borne multidrug resistance is recognized as one of the main challenges in modern medicine, the adaptive forces shaping the evolution of these plasmids within pathogenic hosts are poorly understood. Here we study plasmid-host adaptations following transfer of a 73 kb conjugative multidrug resistance plasmid to naïve clinical isolates of Klebsiella pneumoniae and Escherichia coli. We use experimental evolution, mathematical modelling and population sequencing to show that the long-term persistence and molecular integrity of the plasmid is highly influenced by multiple factors within a 25 kb plasmid region constituting a host-dependent burden. In the E. coli hosts investigated here, improved plasmid stability readily evolves via IS26 mediated deletions of costly regions from the plasmid backbone, effectively expanding the host-range of the plasmid. Although these adaptations were also beneficial to plasmid persistence in a naïve K. pneumoniae host, they were never observed in this species, indicating that differential evolvability can limit opportunities of plasmid adaptation. While insertion sequences are well known to supply plasmids with adaptive traits, our findings suggest that they also play an important role in plasmid evolution by maintaining the plasticity necessary to alleviate plasmid-host constrains. Further, the observed evolutionary strategy consistently followed by all evolved E. coli lineages exposes a trade-off between horizontal and vertical transmission that may ultimately limit the dissemination potential of clinical multidrug resistance plasmids in these hosts.
| S-EPMC5062321 | biostudies-literature
Project description:Conjugative plasmids are the main vehicle for the horizontal spread of antimicrobial resistance (AMR). Although AMR plasmids provide advantages to their hosts under antibiotic pressure, they can also disrupt the cell’s regulatory network, impacting the fitness of their hosts. Despite the importance of plasmid-bacteria interactions on the evolution of AMR, the effects of plasmid carriage on host physiology has remained underexplored, and most studies have focused on model bacteria and plasmids that lack clinical relevance. Here, we analyzed the transcriptional response of 11 clinical enterobacterial strains (2 Escherichia coli, 1 Citrobacter freundii and 8 Klebsiella spp.) and the laboratory-adapted E. coli MG1655 to carriage of pOXA-48, one of the most widely spread carbapenem-resistance plasmids. Our analyses revealed that pOXA-48 produces variable responses on their hosts, but commonly affects processes related to metabolism, transport, response to stimulus, cellular organization and motility. More notably, the presence of pOXA-48 caused an increase in the expression of a small chromosomal operon of unknown function in Klebsiella spp. and C. freundii, which is not present in E. coli. Phylogenetic analysis suggested that this operon has been horizontally mobilized across different Proteobacteria species. We demonstrate that a pOXA-48-encoded LysR transcriptional regulator controls the expression of the operon in Klebsiella spp. and C. freundii. In summary, our results highlight a crosstalk between pOXA-48 and the chromosome of its natural hosts.
2024-07-16 | GSE269852 | GEO
Project description:Plasmid maintenance costs to bacterial hosts is closely linked to the mechanisms that underlie plasmid fitness and how these costs are resolved. Herein, we performed multiple (63) serial passage to explore the compensatory mechanisms of co-evolution of multidrug-resistant IncHI2 plasmid pJXP9 and S. Typhimurium strain ATCC 14028 with or without antibiotic selection. pJXP9 could be maintained at for hundreds of generations even without drug exposure. Decreased lag times and higher competitive advantages were observed in end-point evolved strains bearing pJXP9 compared to ancestral strains. Genomic and transcriptomic analyses revealed that the fitness costs of pJXP9 in ATCC 14028 were derived from not only specific plasmid genes, particularly the multidrug-resistant region and conjugation transfer region I, but also the conflicts resulting from chromosomal gene interactions. Correspondingly, plasmid-borne deletions of these regions could compensate the fitness cost due to the presence of the plasmid. Furthermore, mutations and mRNA alterations in chromosomal genes involved in physiological functions were also adaptative. These functions included decreased flagellar motility, oxidative stress resistance and fumaric acid synthesis, and increased Cu resistance. Our findings suggest that plasmid maintenance through plasmid-bacteria co-evolution is a trade-off between increasing plasmid vertical transmission and impairing its horizontal transmission and bacterial physiological phenotypes.
2022-03-02 | GSE197475 | GEO
Project description:<p>Gut environments harbour dense microbial ecosystems in which plasmids are widely distributed. Plasmids facilitate the exchange of genetic material among microorganisms while enabling the transfer of a diverse array of accessory functions. However, their precise impact on microbial community composition and function remains largely unexplored. Here we identify a prevalent bacterial toxin and a plasmid-encoded resistance mechanism that mediates the interaction between Lactobacilli and Enterococci. This plasmid is widespread across ecosystems, including the rumen and human gut microbiota. Biochemical characterization of the plasmid revealed a defence mechanism against reuterin, a toxin produced by various gut microbes, such as Limosilactobacillus reuteri. Using a targeted metabolomic approach, we find reuterin to be prevalent across rumen ecosystems with impacts on microbial community structure. Enterococcus strains carrying the protective plasmid were isolated and their interactions with L. reuteri, the toxin producer, were studied in vitro. Interestingly, we found that by conferring resistance against reuterin, the plasmid mediates metabolic exchange between the defending and the attacking microbial species, resulting in a beneficial relationship or mutualism. Hence, we reveal here an ecological role for a plasmid-coded defence system in mediating a beneficial interaction. </p>
2023-08-10 | MTBLS7248 | MetaboLights
Project description:Tracking of antibiotic resistance transfer and rapid plasmid evolution in a hospital setting by Nanopore sequencing.
| PRJEB31907 | ENA
Project description:Plasmids facilitate the vertical and horizontal spread of antimicrobial resistance genes between bacteria. The host range and adaptation of plasmids to new hosts determine their impact on the spread of resistance. In this work, we explore the mechanisms driving plasmid adaptation to novel hosts in experimental evolution. Using the small multicopy plasmid pB1000, usually found in Pasteurellaceae, we studied its adaptation to a host from a different bacterial family, Escherichia coli. We observed two different mechanisms of adaptation. One mechanism is single nucleotide polymorphisms (SNPs) in the origin of replication (oriV) of the plasmid, which increase the copy number in E. coli cells, elevating the stability, and resistance profile. The second mechanism consists of two insertion sequences (ISs), IS1 and IS10, which decrease the fitness cost of the plasmid by disrupting an uncharacterized gene on pB1000 that is harmful to E. coli. Both mechanisms increase the stability of pB1000 independently, but only their combination allows long-term maintenance. Crucially, we show that the mechanisms have a different impact on the host range of the plasmid. SNPs in oriV prevent the replication in the original host, resulting in a shift of the host range. In contrast, the introduction of ISs either shifts or expands the host range, depending on the IS. While IS1 leads to expansion, IS10 cannot be reintroduced into the original host. This study gives new insights into the relevance of ISs in plasmid-host adaptation to understand the success in spreading resistance. IMPORTANCE ColE1-like plasmids are small, mobilizable plasmids that can be found across at least four orders of Gammaproteobacteria and are strongly associated with antimicrobial resistance genes. Plasmid pB1000 carries the gene blaROB-1, conferring high-level resistance to penicillins and cefaclor. pB1000 has been described in various species of the family Pasteurellaceae, for example, in Haemophilus influenzae, which can cause diseases such as otitis media, meningitis, and pneumonia. To understand the resistance spread through horizontal transfer, it is essential to study the mechanisms of plasmid adaptation to novel hosts. In this work we identify that a gene from pB1000, which encodes a peptide that is toxic for E. coli, and the low plasmid copy number (PCN) of pB1000 in E. coli cells are essential targets in the described plasmid-host adaptation and therefore limit the spread of pB1000-encoded blaROB-1. Furthermore, we show how the interplay of two adaptation mechanisms leads to successful plasmid maintenance in a different bacterial family.
| S-EPMC10294622 | biostudies-literature
Project description:The type VI secretion system (T6SS) is a highly sophisticated nanomachine widely used by bacteria to achieve competitive advantage and to potentiate horizontal gene transfer. Plasmid conjugation plays crucial roles in bacterial evolution by driving adaptation to environmental stimuli and pathogenicity. The lethal effect mediated by T6SS is detrimental to horizontal gene transfer by conjugation, while bacteria have evolved T6SS repression mechanisms regulated by plasmid to accomplish conjugative transfer. Two TetR family regulators encoded by large conjugative plasmid (LCP) in Acinetobacter baumannii have been proved similar in T6SS restriction, which seems redundant in function. Here, the global regulation roles and multiple DNA binding sites of two plasmid-sourced TetRs were identified. The two TetRs showed distinct preferences in similar roles of T6SS inhibition and binding with DNA probes. Crystal structures of TetRs were solved for illuminating the regulatory mechanism and possible reasons for difference in functions. In addition, plasmid-sourced TetRs also significantly downregulated biofilm formation and bacterial colonization, as well as influenced bacterial virulence in cultured cells and murine pneumonia infection models. Taken together, this work comprehensively elucidates the roles and regulatory mechanisms of TetRs and clarifies their similarity and difference in function, providing insights into plasmid encoded chromosome regulation pathways.
2025-08-16 | GSE277926 | GEO
Project description:The type VI secretion system (T6SS) is a highly sophisticated nanomachine widely used by bacteria to achieve competitive advantage and to potentiate horizontal gene transfer. Plasmid conjugation plays crucial roles in bacterial evolution by driving adaptation to environmental stimuli and pathogenicity. The lethal effect mediated by T6SS is detrimental to horizontal gene transfer by conjugation, while bacteria have evolved T6SS repression mechanisms regulated by plasmid to accomplish conjugative transfer. Two TetR family regulators encoded by large conjugative plasmid (LCP) in Acinetobacter baumannii have been proved similar in T6SS restriction, which seems redundant in function. Here, the global regulation roles and multiple DNA binding sites of two plasmid-sourced TetRs were identified. The two TetRs showed distinct preferences in similar roles of T6SS inhibition and binding with DNA probes. Crystal structures of TetRs were solved for illuminating the regulatory mechanism and possible reasons for difference in functions. In addition, plasmid-sourced TetRs also significantly downregulated biofilm formation and bacterial colonization, as well as influenced bacterial virulence in cultured cells and murine pneumonia infection models. Taken together, this work comprehensively elucidates the roles and regulatory mechanisms of TetRs and clarifies their similarity and difference in function, providing insights into plasmid encoded chromosome regulation pathways.
2025-08-16 | GSE277925 | GEO