Intra- and interpopulation transposition of mobile genetic elements driven by antibiotic selection

Yao, Yi; Maddamsetti, Rohan; Weiss, Andrea; Ha, Yuanchi; Wang, Teng; Wang, Shangying; Li, You

doi:10.1038/s41559-022-01705-2

Cited by 52 publications

(32 citation statements)

References 74 publications

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“…Plasmids are known to contain many transposable elements and integrons that facilitate the translocation of ARGs within and between replicons (9). In contrast, phages typically have very few if any such elements (73).…”

Section: Discussionmentioning

confidence: 99%

“…Numbers indicated above non-homologous cassettes represent different types of ARGs: [1,14]:ant(2'')-Ia, [2]:aac(6')-33, [3,13,19]:qacEΔ1, [4]:aac(3)-Ib, [5]:dfrA15, [6]:arr-2, [7]:group II intron reverse transcriptase/maturase, [8]:aac(6')-Ib, [9]:blaCARB-2, [10,17,25]:aadA2, [11]:cmlA6, [12]:catB11, [15,20]:dfrA12, [16,21,24]:DUF1010 protein, [18]:aac(3)-VIa, [22]:blaGES-1, [23]:arr-6.…”

Section: Antibiotic Resistance Genes Are Common In Phage-plasmids But...mentioning

confidence: 99%

“…Transfer is also facilitated by the presence of mobile genetic elements (MGEs) translocating genetic information between replicons (8). Notably, ARGs are often flanked by transposable elements that facilitate their translocation between plasmids or between plasmids and the chromosome (9). Integrons can also facilitate the translocation of ARG cassettes (10).…”

Section: Introductionmentioning

confidence: 99%

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Phage-plasmids spread antibiotic resistance genes through infection and lysogenic conversion

Pfeifer

Bonnin

Rocha

2022

Preprint

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Antibiotic resistance is rapidly spreading by horizontal transfer of resistance genes in mobile genetic elements. While plasmids are key drivers of this process, very few integrative phages encode antibiotic resistance genes. Here, we find that phage-plasmids, elements that are both phages and plasmids, often carry antibiotic resistance genes. We found 60 phage-plasmids with 184 antibiotic resistance genes, including broad-spectrum-cephalosporins, carbapenems, aminoglycosides, fluoroquinolones and colistin. These genes are in a few hotspots, seem to have been co-translocated with transposable elements, and are often in class I integrons, which had not been previously found in phages. We tried to induce six phage-plasmids with resistance genes (including four with resistance integrons) and succeeded in five cases. Other phage-plasmids and integrative prophages were co-induced in these experiments. As a proof of principle, we focused on a P1-like element encoding an extended spectrum β-lactamase, blaCTX-M-55. After induction, we confirmed that it is capable to infect and convert four other E. coli strains. Its re-induction led to further conversion of a sensitive strain, confirming it is a fully functional phage. This study shows that phage-plasmids carry a large diversity of clinically relevant antibiotic resistance genes that they transfer across bacteria. As plasmids, these elements seem very plastic and capable of acquiring genes from other plasmids. As phages, they may provide novel paths of transfer for resistance genes, because they can infect bacteria distant in time and space from the original host. As a matter of alarm, they may also eventually mediate transfer to other types of phages.

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Section: Discussionmentioning

confidence: 99%

Section: Antibiotic Resistance Genes Are Common In Phage-plasmids But...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Phage-plasmids spread antibiotic resistance genes through infection and lysogenic conversion

Pfeifer

Bonnin

Rocha

2022

Preprint

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“…AMR is a dominant global health concern (Antimicrobial Resistance Collaborators 2022) that is caused by antibiotics in the environment and exacerbated by plasmid-driven AMR gene HGT (Crofts et al 2017, Yao et al 2022). HGT has been the major process shaping bacterial genome structure in E. coli , more so than gene duplication (Lercher & Pál 2008, Price et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Bacterial plasmid-associated and chromosomal proteins have fundamentally different properties in protein interaction networks

Downing

Rahm

2022

Preprint

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Plasmid-encoded genes facilitate the spread of antimicrobial resistance (AMR) though horizontal gene transfer (HGT). HGT driven by plasmids enables the diversification of pathogens into new anatomical and environmental niches, implying that plasmid-bourne genes can cooperate well with chromosomal genes. It is hypothesised that such mobile genes are functionally different to chromosomal ones due to this ability to encode non-essential functions like AMR and traverse distinct host cells. The effect of plasmid-related gene gain on protein-protein interaction network topology is an important question in this area. Moreover, the extent to which these chromosomally- and plasmid-encoded proteins interact with proteins from their own groups compared to the levels with the other group remains unclear. Here, we examined the incidence and protein-protein interactions of all known plasmid-linked genes (n=9,172) across representative specimens from all bacteria (n=4,419) using all known unique plasmids. We found that such plasmid-related genes constitute on average of 10.5% of the total number of genes per bacterial sample, and that plasmid genes preferentially associated with different species such that provide moderate taxonomical power. Surprisingly, plasmid-related proteins had both more direct and indirect protein-protein interactions compared to chromosomal proteins, countering the hypothesis that genes with higher mobility rates should have fewer protein-level interactions. Nonetheless, topological analysis and investigation of the protein-protein interaction networks’ connectivity and change in the number of independent components demonstrated that the plasmid-related proteins had limited overall impact in most bacterial samples (>94%). This paper assembled extensive data on plasmid-related proteins, their interactions and associations with diverse bacterial specimens that is available for the community to investigate in more detail.Significance as a bioresource to the communityThis paper outlines the compilation and analysis of bacterial plasmid-encoded genes and protein-level interactions that will be a useful resource for the community. All input data, output data, code and high-resolution figures is available on FigShare and Github. We extracted protein-protein interaction data for all available valid bacterial samples (n=4,419) to differentiate plasmid-related genes and PPIs from chromosomal ones. We compiled all known unique plasmids (n=18,628) to identify 9,172 unique plasmid-related genes using gene name information, which may require refinement is a useful resource for the community because we found that these had some power to resolve known taxonomic differences, suggesting host-gene co-evolution. The co-varying plasmid-related genes and samples are available for more specific testing. We used this data to identify protein-protein interactions involving plasmid proteins per sample, and showed that plasmid-related proteins tended here to have more protein-protein interactions than chromosomal ones. However, this varied across samples, and thus data allows the community to explore features of selected bacteria and/or genes. We identified a small number of samples (n=158) where the plasmid-related proteins had major effects on protein-protein interaction network structure, which is possible to explore more through this bioresource.

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“…The misuse and overuse of antibiotics, as the key driving force in the evolution and propagation of antibiotic resistance genes (ARGs), has caused ecological and human health risks, attracting the global attention (1)(2)(3). As the selection pressure posed by antibiotics was not strictly specific, long-term exposure to single or several antibiotics, especially those used widely and extensively, could accelerate the co-evolution of multiple ARGs (4)(5)(6). Amphenicol antibiotics, include chloramphenicol (CAP), its congener thiamphenicol (TAP) and florfenicol.…”

Section: Introductionmentioning

confidence: 99%

The Molecular Mechanism of Chloramphenicol and Thiamphenicol Resistance Mediated by a Novel Oxidase CmO in Sphingomonadaceae

Zhang

Ren

et al. 2022

Preprint

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Antibiotic resistance mediated by bacterial enzyme inactivation plays a mysterious and crucial role for antibiotic degradation and selection pressure reduction in the environment. The enzymatic inactivation of the antibiotic chloramphenicol (CAP) involves nitro reduction, amide bond hydrolysis and acetylation modification. However, the molecular mechanism of enzymatic oxidation of CAP remains unknown. Here, a novel oxidase gene cmO was identified and confirmed biochemically to catalyze the resistance process through the oxidative inactivation at the side chain C-3' position of CAP and thiamphenicol (TAP) in Sphingomonadaceae. The oxidase CmO is highly conservative in Sphingomonadaceae and shares the highest amino acid homology of 41.05% with the biochemically identified glucose methanol choline (GMC) oxidoreductases. Molecular docking and site-directed mutagenesis analyses demonstrated that CAP was anchored inside the protein pocket of CmO with the hydrogen bonding of key residues glycine (G)99, asparagine (N)518, methionine (M)474 and tyrosine (Y)380. CAP sensitivity test demonstrated that the acetyltransferase and CmO showed higher resistance to CAP as compared with the amide bond-hydrolyzing esterase and nitroreductase. This study provides a better theoretical basis and a novel diagnostic gene for understanding and assessing the fate and resistance risk of CAP and TAP in the environment.

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Intra- and interpopulation transposition of mobile genetic elements driven by antibiotic selection

Cited by 52 publications

References 74 publications

Phage-plasmids spread antibiotic resistance genes through infection and lysogenic conversion

Phage-plasmids spread antibiotic resistance genes through infection and lysogenic conversion

Bacterial plasmid-associated and chromosomal proteins have fundamentally different properties in protein interaction networks

The Molecular Mechanism of Chloramphenicol and Thiamphenicol Resistance Mediated by a Novel Oxidase CmO in Sphingomonadaceae

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