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

Abstract

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).

The bacterial capsule is a gatekeeper for mobile DNA

“…https://doi.org/10.1371/journal. pbio.3001308 elegant study from the Microbial Evolutionary Genomics group (Institut Pasteur, Paris), Haudiquet and colleagues combined sophisticated in silico and in vitro approaches to shed new light on this topic [5]. After comprehensively analyzing ca.…”

IntegronFinder 2.0: identification and analysis of integrons across Bacteria, with a focus on antibiotic resistance in Klebsiella

“…We computed the species phylogenetic tree with IQ-TREE, as explained in [31]. Briefly, the 1,431 protein families of the persistent genome (gene families present in more than 99% of the strains in a single copy) were aligned with Mafft (v7.407) [32], back-translated to DNA and concatenated.…”

“…Klebsiella data. The Klebsiella genomes were downloaded and annotated with PanACoTA [28] as explained in [31]. Briefly, we downloaded all the 5805 genome assemblies labelled as Klebsiella pneumoniae sensu stricto (Kpn) from NCBI RefSeq (accessed on October 10 th 2018).…”

Plasmid co-infection: linking biological mechanisms to ecological and evolutionary dynamics

“…R. Soc. B 377: 20200478 associated systems) [63,79,80], or by affecting cell envelope composition [81].…”

“…Plasmids can also affect the entry and establishment of other variants into a cell ‘in trans ’, for example via restriction modification (RM) systems and CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR associated systems) [ 63 , 79 , 80 ], or by affecting cell envelope composition [ 81 ].…”