4.6 Article

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

Journal

PLOS BIOLOGY
Volume 19, Issue 7, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.3001276

Keywords

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Funding

  1. ANR JCJC (Agence national de recherche) [ANR 18 CE12 0001 01]
  2. Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' grant [ANR-10-LABX-62-IBEID]
  3. INCEPTION program [PIA/ANR-16-CONV-0005]
  4. FRM [EQU201903007835]
  5. FIRE Doctoral School (Centre de Recherche Interdisciplinaire, programme Bettencourt)
  6. Agence Nationale de la Recherche (ANR) [ANR-18-CE12-0001] Funding Source: Agence Nationale de la Recherche (ANR)

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Mobile genetic elements (MGEs) facilitate genetic transfer between bacteria by interacting with the cellular envelope, with capsules acting as the first barrier in some cases. Capsules drive gene flow among related serotypes, with phage predation leading to frequent capsule gene inactivation. Acquisition of conjugative plasmids is higher in isolates lacking functional capsules, and capsule inactivation by phage pressure may facilitate subsequent reacquisition by conjugation. This process of loss and regain rewires gene flow, particularly between chemically related serotypes, impacting the fitness of strains and potentially facilitating acquisition of antibiotic resistance genes.
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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