Ruiz-Garbajosa, P. | bioRxiv Science

bioRxiv2020

The distribution of plasmid fitness effects explains plasmid persistence in bacterial communities

Introductory paragraphPlasmid persistence in bacterial populations is strongly influenced by the fitness effects associated with plasmid carriage. However, plasmid fitness effects in wild-type bacterial hosts remain largely unexplored. In this study, we determined the distribution of fitness effects (DFE) for the major antibiotic resistance plasmid pOXA-48 in wild-type, ecologically compatible enterobacterial isolates from the human gut microbiota. Our results show that although pOXA-48 produced an overall reduction in bacterial fitness, the DFE was dominated by quasi-neutral effects, and beneficial effects were observed in several isolates. Incorporating these data into a simple population dynamics model revealed a new set of conditions for plasmid stability in bacterial communities, with plasmid persistence increasing with bacterial diversity and becoming less dependent on conjugation. Moreover, genomic results showed a link between plasmid fitness effects and bacterial phylogeny, helping to explain pOXA-48 epidemiology. Our results provide a simple and general explanation for plasmid persistence in natural bacterial communities.

microbiology↗

bioRxiv2020

Dissemination routes of the carbapenem resistance plasmid pOXA-48 in a hospital setting

Introductory paragraphInfections caused by carbapenemase-producing enterobacteria (CPE) are a major concern in clinical settings worldwide. Two fundamentally different processes shape the epidemiology of CPE in hospitals: the dissemination of CPE clones from patient to patient (between-patient transfer), and the transfer of carbapenemase-encoding plasmids between enterobacteria in the gut microbiota of individual patients (within-patient transfer). The relative contribution of each process to the overall dissemination of carbapenem resistance in hospitals remains poorly understood. Here, we used mechanistic models combining epidemiological data from more than 9,000 patients with whole genome sequence information from 250 enterobacteria clones to characterise the dissemination routes of the carbapenemase-encoding plasmid pOXA-48 in a hospital setting over a two-year period. Our results revealed frequent between-patient transmission of high-risk pOXA-48-carrying clones, mostly of Klebsiella pneumoniae and sporadically Escherichia coli. The results also identified pOXA-48 dissemination hotspots within the hospital, such as specific wards and individual rooms within wards. Using high-resolution plasmid sequence analysis, we uncovered the pervasive within-patient transfer of pOXA-48, suggesting that horizontal plasmid transfer occurs in the gut of virtually every colonised patient. The complex and multifaceted epidemiological scenario exposed by this study provides new insights for the development of intervention strategies to control the in-hospital spread of CPE.

microbiology↗