Rapid evolutionary turnover of mobile genetic elements drives microbial resistance to viruses

AbstractAlthough it is generally accepted that viruses (phages) drive bacterial evolution, how these dynamics play out in the wild remains poorly understood. Here we show that the arms race between phages and their hosts is mediated by large and highly diverse mobile genetic elements. These phage-defense elements display exceedingly fast evolutionary turnover, resulting in differential phage susceptibility among clonal bacterial strains while phage receptors remain invariant. Protection afforded by multiple elements is cumulative, and a single bacterial genome can harbor as many as 18 putative phage-defense elements. Overall, elements account for 90% of the flexible genome amongst closely related strains. The rapid turnover of these elements demonstrates that phage resistance is unlinked from other genomic features and that resistance to phage therapy might be as easily acquired as antibiotic resistance.

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Similarity in the Structure of tetD-Carrying Mobile Genetic Elements in Bacterial Strains of Different Genera Isolated from Cultured Yellowtail

Biocontrol Science ◽

10.4265/bio.21.183 ◽

2016 ◽

Vol 21 (3) ◽

pp. 183-186 ◽

Cited By ~ 1

Author(s):

MANABU FURUSHITA ◽

HIROSHI AKAGI ◽

AZUSA KANEOKA ◽

TOSHIMICHI MAEDA ◽

TSUBASA FUKUDA ◽

...

Keyword(s):

Mobile Genetic Elements ◽

Bacterial Strains ◽

Genetic Elements

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Properties of genes encoding transfer RNAs as integration sites for genomic islands and prophages in Klebsiella pneumoniae

10.1101/2020.11.02.365908 ◽

2020 ◽

Author(s):

Camilo Berríos-Pastén ◽

Rodolfo Acevedo ◽

Patricio Arros ◽

Macarena A. Varas ◽

Kelly L. Wyres ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Integration Site ◽

Phylogenetic Analyses ◽

Bacterial Genome ◽

Mobile Genetic Elements ◽

Genomic Islands ◽

Genomic Context ◽

Genetic Elements ◽

Genes Encoding ◽

Integration Sites

ABSTRACTThe evolution of traits including antibiotic resistance, virulence, and increased fitness in Klebsiella pneumoniae and related species has been linked to the acquisition of mobile genetic elements through horizontal transfer. Among them, genomic islands (GIs) preferentially integrating at genes encoding tRNAs and the tmRNA (t(m)DNAs) would be significant in promoting chromosomal diversity. Here, we studied the whole set of t(m)DNAs present in 66 Klebsiella chromosomes, investigating their usage as integration sites and the properties of the integrated GIs. A total of 5,624 t(m)DNAs were classified based on their sequence conservation, genomic context, and prevalence. 161 different GIs and prophages were found at these sites, hosting 3,540 gene families including various related to virulence and drug resistance. Phylogenetic analyses supported the acquisition of several of these elements through horizontal gene transfer, likely mediated by a highly diverse set of encoded integrases targeting specific t(m)DNAs and sublocations inside them. Only a subset of the t(m)DNAs had integrated GIs and even identical tDNA copies showed dissimilar usage frequencies, suggesting that the genomic context would influence the integration site selection. This usage bias, likely towards avoiding disruption of polycistronic transcriptional units, would be conserved across Gammaproteobacteria. The systematic comparison of the t(m)DNAs across different strains allowed us to discover an unprecedented number of K. pneumoniae GIs and prophages and to raise important questions and clues regarding the fundamental properties of t(m)DNAs as targets for the integration of mobile genetic elements and drivers of bacterial genome evolution and pathogen emergence.

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Prediction of prophages and their host ranges in pathogenic and commensal Neisseria species

10.1101/2021.12.16.473053 ◽

2021 ◽

Author(s):

Giulia Orazi ◽

Alan J Collins ◽

Rachel J Whitaker

Keyword(s):

Gene Transfer ◽

Horizontal Gene Transfer ◽

Bacterial Genome ◽

Mobile Genetic Elements ◽

Pathogenic Species ◽

Chromosomal Dna ◽

Bacterial Physiology ◽

Neisseria Species ◽

Genetic Elements ◽

Commensal Neisseria

The genus Neisseria includes two pathogenic species, N. gonorrhoeae and N. meningitidis, and numerous commensal species. Neisseria species frequently exchange DNA with one other, primarily via transformation and homologous recombination, and via multiple types of mobile genetic elements (MGEs). Few Neisseria bacteriophages (phages) have been identified and their impact on bacterial physiology is poorly understood. Furthermore, little is known about the range of species that Neisseria phages can infect. In this study, we used three virus prediction tools to scan 248 genomes of 21 different Neisseria species and identified 1302 unique predicted prophages. Using comparative genomics, we found that many predictions are dissimilar from other prophages and MGEs previously described to infect Neisseria species. We also identified similar predicted prophages in genomes of different Neisseria species. Additionally, we examined CRISPR-Cas targeting of each Neisseria genome and predicted prophage. While CRISPR targeting of chromosomal DNA appears to be common among several Neisseria species, we found that 20% of the prophages we predicted are targeted significantly more than the rest of the bacterial genome in which they were identified (i.e., backbone). Furthermore, many predicted prophages are targeted by CRISPR spacers encoded by other species. We then used these results to infer additional host species of known Neisseria prophages and predictions that are highly targeted relative to the backbone. Together, our results suggest that we have identified novel Neisseria prophages, several of which may infect multiple Neisseria species. These findings have important implications for understanding horizontal gene transfer between members of this genus. IMPORTANCE: Drug-resistant N. gonorrhoeae is a major threat to human health. Commensal Neisseria species are thought to serve as reservoirs of antibiotic resistance and virulence genes for the pathogenic species N. gonorrhoeae and N. meningitidis. Therefore, it is important to understand both the diversity of mobile genetic elements (MGEs) that can mediate horizontal gene transfer within this genus, and the breadth of species these MGEs can infect. In particular, few bacteriophages (phages) have been identified and characterized in Neisseria species. In this study, we identified a large number of candidate phages integrated within the genomes of commensal and pathogenic Neisseria species, many of which appear to be novel phages. Importantly, we discovered extensive interspecies targeting of predicted phages by Neisseria CRISPR-Cas systems, which may reflect their movement between different species. Uncovering the diversity and host range of phages is essential for understanding how they influence the evolution of their microbial hosts.

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Bacterial transformation buffers environmental fluctuations through the reversible integration of mobile genetic elements

10.1101/557462 ◽

2019 ◽

Author(s):

Gabriel Carvalho ◽

David Fouchet ◽

Gonché Danesh ◽

Anne-Sophie Godeux ◽

Maria-Halima Laaberki ◽

...

Keyword(s):

Resistance Genes ◽

Bacterial Genome ◽

Antibiotic Resistance Genes ◽

Mobile Genetic Elements ◽

Host Cells ◽

Transformation Rate ◽

Bacterial Cells ◽

Bacterial Populations ◽

Genetic Elements ◽

Intermediate Transformation

AbstractHorizontal gene transfer (HGT) is known to promote the spread of genes in bacterial communities, which is of primary importance to human health when these genes provide resistance to antibiotics. Among the main HGT mechanisms, natural transformation stands out as being widespread and encoded by the bacterial core genome. From an evolutionary perspective, transformation is often viewed as a mean to generate genetic diversity and mixing within bacterial populations. However, another recent paradigm proposes that its main evolutionary function would be to cure bacterial genomes from their parasitic mobile genetic elements (MGEs). Here, we propose to combine these two seemingly opposing points of view because MGEs, although costly for bacterial cells, can carry functions that are point-in-time beneficial to bacteria under stressful conditions (e.g. antibiotic resistance genes under antibiotic exposure). Using computational modeling, we show that, in stochastic environments (unpredictable stress exposure), an intermediate transformation rate maximizes bacterial fitness by allowing the reversible integration of MGEs carrying resistance genes but costly for the replication of host cells. By ensuring such reversible genetic diversification (acquisition then removal of MGEs), transformation would be a key mechanism for stabilizing the bacterial genome in the long term, which would explain its striking conservation.

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Discovering complete quasispecies in bacterial genomes

10.1101/119743 ◽

2017 ◽

Author(s):

Frederic Bertels ◽

Chaitanya S. Gokhale ◽

Arne Traulsen

Keyword(s):

Natural Populations ◽

Mobile Genetic Elements ◽

Small Range ◽

Mutational Load ◽

Bacterial Strains ◽

Bacterial Genomes ◽

Genetic Elements ◽

Quasispecies Model ◽

A Genome ◽

Almost All

ABSTRACTMobile genetic elements can be found in almost all genomes. Possibly the most common non-autonomous mobile genetic elements in bacteria are REPINs that can occur hundreds of times within a genome. The sum of all REPINs within a genome are an evolving populations because they replicate and mutate. We know the exact composition of this population and the sequence of each member of a REPIN population, in contrast to most other biological populations. Here, we model the evolution of REPINs as quasispecies. We fit our quasispecies model to ten different REPIN populations from ten different bacterial strains and estimate duplication rates. We find that our estimated duplication rates range from about 5 × 10−9to 37 × 10−9duplications per generation per genome. The small range and the low level of the REPIN duplication rates suggest a universal trade-off between the survival of the REPIN population and the reduction of the mutational load for the host genome. The REPIN populations we investigated also possess features typical of other natural populations. One population shows hallmarks of a population that is going extinct, another population seems to be growing in size and we also see an example of competition between two REPIN populations.

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The novel macrolide resistance genes mef(F) and msr(G) are located on a plasmid in Macrococcus canis and a transposon in Macrococcus caseolyticus

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa405 ◽

2020 ◽

Vol 76 (1) ◽

pp. 48-54

Author(s):

Javier Eduardo Fernandez ◽

Vincent Perreten ◽

Sybille Schwendener

Keyword(s):

Resistance Genes ◽

Resistance Mechanism ◽

Mobile Genetic Elements ◽

Bioinformatic Analysis ◽

Membered Ring ◽

Macrolide Resistance ◽

The Novel ◽

Bacterial Strains ◽

Chloramphenicol Resistance ◽

Genetic Elements

Abstract Objectives To analyse macrolide resistance in a Macrococcus canis strain isolated from a dog with an ear infection, and determine whether the resistance mechanism is also present in other bacteria, and associated with mobile genetic elements. Methods The whole genome of M. canis Epi0082 was sequenced using PacBio and Illumina technologies. Novel macrolide resistance determinants were identified through bioinformatic analysis, and functionality was demonstrated by expression in Staphylococcus aureus. Mobile genetic elements containing the novel genes were analysed in silico for strain Epi0082 as well as in other bacterial strains deposited in GenBank. Results M. canis Epi0082 contained a 3212 bp operon with the novel macrolide resistance genes mef(F) and msr(G) encoding a efflux protein and an ABC-F ribosomal protection protein, respectively. Cloning in S. aureus confirmed that both genes individually confer resistance to the 14- and 15-membered ring macrolides erythromycin and azithromycin, but not the 16-membered ring macrolide tylosin. A reduced susceptibility to the streptogramin B pristinamycin IA was additionally observed when msr(G) was expressed in S. aureus under erythromycin induction. Epi0082 carried the mef(F)–msr(G) operon together with the chloramphenicol resistance gene fexB in a novel 39 302 bp plasmid pMiCAN82a. The mef(F)–msr(G) operon was also found in macrolide-resistant Macrococcus caseolyticus strains in the GenBank database, but was situated in the chromosome as part of a novel 13 820 bp or 13 894 bp transposon Tn6776. Conclusions The identification of mef(F) and msr(G) on different mobile genetic elements in Macrococcus species indicates that these genes hold potential for further dissemination of resistance to the clinically important macrolides in the bacterial population.

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Bacterial Transformation Buffers Environmental Fluctuations through the Reversible Integration of Mobile Genetic Elements

mBio ◽

10.1128/mbio.02443-19 ◽

2020 ◽

Vol 11 (2) ◽

Cited By ~ 2

Author(s):

Gabriel Carvalho ◽

David Fouchet ◽

Gonché Danesh ◽

Anne-Sophie Godeux ◽

Maria-Halima Laaberki ◽

...

Keyword(s):

Horizontal Gene Transfer ◽

Resistance Genes ◽

Natural Transformation ◽

Bacterial Genome ◽

Mobile Genetic Elements ◽

Bacterial Populations ◽

Genetic Elements ◽

Intermediate Transformation ◽

Bacterial Fitness

ABSTRACT Horizontal gene transfer (HGT) promotes the spread of genes within bacterial communities. Among the HGT mechanisms, natural transformation stands out as being encoded by the bacterial core genome. Natural transformation is often viewed as a way to acquire new genes and to generate genetic mixing within bacterial populations. Another recently proposed function is the curing of bacterial genomes of their infectious parasitic mobile genetic elements (MGEs). Here, we propose that these seemingly opposing theoretical points of view can be unified. Although costly for bacterial cells, MGEs can carry functions that are at points in time beneficial to bacteria under stressful conditions (e.g., antibiotic resistance genes). Using computational modeling, we show that, in stochastic environments, an intermediate transformation rate maximizes bacterial fitness by allowing the reversible integration of MGEs carrying resistance genes, although these MGEs are costly for host cell replication. Based on this dual function (MGE acquisition and removal), transformation would be a key mechanism for stabilizing the bacterial genome in the long term, and this would explain its striking conservation. IMPORTANCE Natural transformation is the acquisition, controlled by bacteria, of extracellular DNA and is one of the most common mechanisms of horizontal gene transfer, promoting the spread of resistance genes. However, its evolutionary function remains elusive, and two main roles have been proposed: (i) the new gene acquisition and genetic mixing within bacterial populations and (ii) the removal of infectious parasitic mobile genetic elements (MGEs). While the first one promotes genetic diversification, the other one promotes the removal of foreign DNA and thus genome stability, making these two functions apparently antagonistic. Using a computational model, we show that intermediate transformation rates, commonly observed in bacteria, allow the acquisition then removal of MGEs. The transient acquisition of costly MGEs with resistance genes maximizes bacterial fitness in environments with stochastic stress exposure. Thus, transformation would ensure both a strong dynamic of the bacterial genome in the short term and its long-term stabilization.

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