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).
Highlights
Mobile genetic elements (MGE) drive horizontal gene transfer (HGT) between bacteria, which may result in the acquisition of virulence factors and antibiotic resistance genes (ARGs) [1,2]
We reasoned that if MGEs are adapted to serotypes, genetic exchanges should be more frequent between bacteria of similar serotypes
Rarefaction curves suggest that we have extensively sampled the genetic diversity of Klebsiella pneumoniae (Kpn) genomes, its capsular locus type (CLT), plasmids, and prophages (Fig 1B)
Summary
Mobile genetic elements (MGE) drive horizontal gene transfer (HGT) between bacteria, which may result in the acquisition of virulence factors and antibiotic resistance genes (ARGs) [1,2]. DNA can be exchanged between cells via virions or conjugative systems [3,4]. Virions attach to specific cell receptors to inject their DNA into the cell, which restricts their host range [5]. Bacteriophages ( phages) may package bacterial DNA and transfer it across cells (transduction). Temperate phages may integrate into the bacterial genome as prophages, eventually changing the host phenotype [4]. DNA transfer by conjugation involves mating pair formation (MPF) between a donor and a recipient cell [6]. Even if phages and conjugative elements use very different mechanisms of DNA transport, both depend crucially on interactions with the cell envelope of the recipient bacterium. Changes in the bacterial cell envelope may affect their rates of transfer
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