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

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.

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

PLoS Biology ◽

10.1371/journal.pbio.3001276 ◽

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).

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Gene flow, mobile genetic elements and the recruitment of antibiotic resistance genes into Gram-negative pathogens

FEMS Microbiology Reviews ◽

10.1111/j.1574-6976.2011.00273.x ◽

2011 ◽

Vol 35 (5) ◽

pp. 790-819 ◽

Cited By ~ 298

Author(s):

Hatch W. Stokes ◽

Michael R. Gillings

Keyword(s):

Antibiotic Resistance ◽

Gene Flow ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Mobile Genetic Elements ◽

Gram Negative ◽

Genetic Elements

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Shotgun metagenomic analysis reveals the prevalence of antibiotic resistance genes and mobile genetic elements in full scale hospital wastewater treatment plants

Journal of Environmental Management ◽

10.1016/j.jenvman.2021.113270 ◽

2021 ◽

Vol 296 ◽

pp. 113270

Author(s):

Ranjith Kumar Manoharan ◽

Sathiyaraj Srinivasan ◽

Gnanendra Shanmugam ◽

Young-Ho Ahn

Keyword(s):

Antibiotic Resistance ◽

Wastewater Treatment ◽

Resistance Genes ◽

Wastewater Treatment Plants ◽

Antibiotic Resistance Genes ◽

Mobile Genetic Elements ◽

Full Scale ◽

Metagenomic Analysis ◽

Hospital Wastewater ◽

Genetic Elements

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

Water ◽

10.3390/w13111461 ◽

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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