scholarly journals Interplay between the cell envelope and mobile genetic elements shapes gene flow in populations of the nosocomial pathogen Klebsiella pneumoniae

PLoS Biology ◽  
2021 ◽  
Vol 19 (7) ◽  
pp. e3001276
Author(s):  
Matthieu Haudiquet ◽  
Amandine Buffet ◽  
Olaya Rendueles ◽  
Eduardo P. C. Rocha
Keyword(s):  
Gene Flow ◽  
Klebsiella Pneumoniae ◽  
Cell Envelope ◽  
Antibiotic Resistance Genes ◽  
Mobile Genetic Elements ◽  
Multidrug Resistant ◽  
Physical Interaction ◽  
Apparent Contradiction ◽  
Genetic Elements ◽  
Trade Offs

Mobile genetic elements (MGEs) drive genetic transfers between bacteria using mechanisms that require a physical interaction with the cellular envelope. In the high-priority multidrug-resistant nosocomial pathogens (ESKAPE), the first point of contact between the cell and virions or conjugative pili is the capsule. While the capsule can be a barrier to MGEs, it also evolves rapidly by horizontal gene transfer (HGT). Here, we aim at understanding this apparent contradiction by studying the covariation between the repertoire of capsule genes and MGEs in approximately 4,000 genomes of Klebsiella pneumoniae (Kpn). We show that capsules drive phage-mediated gene flow between closely related serotypes. Such serotype-specific phage predation also explains the frequent inactivation of capsule genes, observed in more than 3% of the genomes. Inactivation is strongly epistatic, recapitulating the capsule biosynthetic pathway. We show that conjugative plasmids are acquired at higher rates in natural isolates lacking a functional capsular locus and confirmed experimentally this result in capsule mutants. This suggests that capsule inactivation by phage pressure facilitates its subsequent reacquisition by conjugation. Accordingly, capsule reacquisition leaves long recombination tracts around the capsular locus. The loss and regain process rewires gene flow toward other lineages whenever it leads to serotype swaps. Such changes happen preferentially between chemically related serotypes, hinting that the fitness of serotype-swapped strains depends on the host genetic background. These results enlighten the bases of trade-offs between the evolution of virulence and multidrug resistance and caution that some alternatives to antibiotics by selecting for capsule inactivation may facilitate the acquisition of antibiotic resistance genes (ARGs).

scholarly journals Interplay between the cell envelope and mobile genetic elements shapes gene flow in populations of a nosocomial pathogen

2020 ◽  
Author(s):  
Matthieu Haudiquet ◽  
Amandine Buffet ◽  
Olaya Rendueles ◽  
Eduardo P.C. Rocha
Keyword(s):  
Gene Flow ◽  
Biosynthetic Pathway ◽  
Cell Envelope ◽  
Antibiotic Resistance Genes ◽  
Mobile Genetic Elements ◽  
Nosocomial Pathogen ◽  
Genetic Elements ◽  
Specific Phage ◽  
Trade Offs ◽  
Evolution Of Virulence

ABSTRACTMobile genetic elements (MGEs) drive genetic transfers between bacteria using mechanisms that are affected by the cell envelope composition, notably the capsule. Here, we show that capsules constrain phage-mediated gene flow between closely related serotypes in Klebsiella pneumoniae, a high-priority nosocomial enterobacteria. Serotype-specific phage pressure may also explain the inactivation of capsule genes, which occur frequently and recapitulate the capsule biosynthetic pathway. We show that plasmid conjugation is increased upon capsule inactivation and that capsule re-acquisition leaves long recombination tracts around the capsular locus. This suggests that capsule inactivation by phage pressure facilitates its subsequent re-acquisition by conjugation, a process re-wiring gene flow towards novel lineages whenever it leads to serotype swaps. These results reveal the basis of trade-offs between the evolution of virulence and multidrug resistance. They also caution that some alternatives to antibiotic therapy may select for capsule inactivation, thus decreasing virulence but facilitating antibiotic resistance genes acquisition.

scholarly journals Antibiotic Resistance and Mobile Genetic Elements in Extensively Drug-Resistant Klebsiella pneumoniae Sequence Type 147 Recovered from Germany

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 675
Author(s):  
Kyriaki Xanthopoulou ◽  
Alessandra Carattoli ◽  
Julia Wille ◽  
Lena M. Biehl ◽  
Holger Rohde ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Mobile Genetic Elements ◽  
Multidrug Resistant ◽  
Genetic Variations ◽  
Drug Resistant ◽  
Genetic Elements ◽  
Resistance Determinants ◽  
Extensively Drug Resistant

Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms followed by core-genome multi-locus sequence typing (MLST). The plasmid content is analysed by conjugation, S1-pulsed-field gel electrophoresis (S1-PFGE) and Southern blot experiments. The K. pneumoniae isolates belong to the international high-risk clone ST147 and form a cluster of closely related isolates. They harbour the blaOXA-181 carbapenemase on a ColKP3 plasmid, and 12 antibiotic resistance determinants on an multidrug-resistant (MDR) IncR plasmid with a recombinogenic nature and encoding a large number of insertion elements. The IncR plasmids within the three isolates share a high degree of homology, but present also genetic variations, such as inversion or deletion of genetic regions in close proximity to MGEs. In addition, six plasmids not harbouring any antibiotic resistance determinants are present in each isolate. Our study indicates that genetic variations can be observed within a cluster of closely related isolates, due to the dynamic nature of MGEs. The mobilome of the K. pneumoniae isolates combined with the emergence of the XDR ST147 high-risk clone have the potential to become a major challenge for global healthcare.

scholarly journals CRISPR-Cas is associated with fewer antibiotic resistance genes in bacterial pathogens

2021 ◽  
Vol 377 (1842) ◽  
Author(s):  
Elizabeth Pursey ◽  
Tatiana Dimitriu ◽  
Fernanda L. Paganelli ◽  
Edze R. Westra ◽  
Stineke van Houte
Keyword(s):  
Antibiotic Resistance ◽  
System Analysis ◽  
Bacterial Pathogens ◽  
Genetic Material ◽  
Antibiotic Resistance Genes ◽  
Mobile Genetic Elements ◽  
Multidrug Resistant ◽  
Human Pathogens ◽  
Genetic Elements ◽  
Defence System

The acquisition of antibiotic resistance (ABR) genes via horizontal gene transfer (HGT) is a key driver of the rise in multidrug resistance amongst bacterial pathogens. Bacterial defence systems per definition restrict the influx of foreign genetic material, and may therefore limit the acquisition of ABR. CRISPR-Cas adaptive immune systems are one of the most prevalent defences in bacteria, found in roughly half of bacterial genomes, but it has remained unclear if and how much they contribute to restricting the spread of ABR. We analysed approximately 40 000 whole genomes comprising the full RefSeq dataset for 11 species of clinically important genera of human pathogens, including Enterococcus , Staphylococcus , Acinetobacter and Pseudomonas . We modelled the association between CRISPR-Cas and indicators of HGT, and found that pathogens with a CRISPR-Cas system were less likely to carry ABR genes than those lacking this defence system. Analysis of the mobile genetic elements (MGEs) targeted by CRISPR-Cas supports a model where this host defence system blocks important vectors of ABR. These results suggest a potential ‘immunocompromised’ state for multidrug-resistant strains that may be exploited in tailored interventions that rely on MGEs, such as phages or phagemids, to treat infections caused by bacterial pathogens. This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.

scholarly journals Mobile Genetic Elements Drive the Antibiotic Resistome Alteration in Freshwater Shrimp Aquaculture

Water ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1461
Author(s):  
Hao Fang ◽  
Nan Ye ◽  
Kailong Huang ◽  
Junnan Yu ◽  
Shuai Zhang
Keyword(s):  
Bacterial Communities ◽  
High Throughput Sequencing ◽  
Procambarus Clarkii ◽  
Variation Partitioning ◽  
Antibiotic Resistance Genes ◽  
Mobile Genetic Elements ◽  
Shrimp Aquaculture ◽  
Sediment Samples ◽  
Genetic Elements ◽  
Freshwater Aquaculture

Shrimp aquaculture environments are a natural reservoir of multiple antibiotic resistance genes (ARGs) due to the overuse of antibiotics. Nowadays, the prevalence of these kinds of emerging contaminants in shrimp aquaculture environments is still unclear. In this study, high-throughput sequencing techniques were used to analyze the distribution of ARGs and mobile genetic elements (MGEs), bacterial communities, and their correlations in water and sediment samples in two types of typical shrimp (Procambarus clarkii and Macrobrachium rosenbergii) freshwater aquaculture environments. A total of 318 ARG subtypes within 19 ARG types were detected in all the samples. The biodiversity and relative abundance of ARGs in sediment samples showed much higher levels compared to water samples from all ponds in the study area. Bacitracin (17.44–82.82%) and multidrug (8.57–49.70%) were dominant ARG types in P. clarkii ponds, while sulfonamide (26.33–39.59%) and bacitracin (12.75–37.11%) were dominant ARG types in M. rosenbergii ponds. Network analysis underlined the complex co-occurrence patterns between bacterial communities and ARGs. Proteobacteria, Cyanobacteria, and Actinobacteria exhibited a high abundance in all samples, in which C39 (OTU25355) and Hydrogenophaga (OTU162961) played important roles in the dissemination of and variation in ARGs based on their strong connections between ARGs and bacterial communities. Furthermore, pathogens (e.g., Aeromonadaceae (OTU195200) and Microbacteriaceae (OTU16033)), which were potential hosts for various ARGs, may accelerate the propagation of ARGs and be harmful to human health via horizontal gene transfer mediated by MGEs. Variation partitioning analysis further confirmed that MGEs were the most crucial contributor (74.76%) driving the resistome alteration. This study may help us to understand the non-ignorable correlations among ARGs, bacterial diversity, and MGEs in the shrimp freshwater aquaculture environments.

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