Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids

• DOI: 10.1128/mbio.01987-16
• Publication Date: 2016-12-07T01:40:21Z
• Authors: Susu He; Michael Chandler; Alessandro M. Varani; Alison B. Hickman; John P. Dekker; Fred Dyda
• Keywords: Recombination, Genetic; 0301 basic medicine; 610; Microbiology; QR1-502; 3. Good health; Evolution, Molecular; Interspersed Repetitive Sequences; 03 medical and health sciences; Enterobacteriaceae; Drug Resistance, Bacterial; Selection, Genetic; Research Article; Plasmids

ABSTRACT The dissemination of resistance among bacteria has been facilitated by the fact that genes are usually located on a diverse and evolving set transmissible plasmids. However, mechanisms generating diversity enabling adaptation within highly successful plasmids have remained obscure, despite their profound clinical significance. To understand these mechanisms, we performed detailed analysis mobilome (the entire mobile genetic element content) previously sequenced carbapenemase-producing Enterobacteriaceae (CPE) from National Institutes Health Clinical Center. This revealed plasmid reorganizations occurring in natural context colonization human hosts were overwhelmingly driven rearrangements carried out replicative transposons working concert with process homologous recombination. A more complete understanding molecular evolutionary forces driving may lead to fundamentally new strategies address problem antibiotic resistance. IMPORTANCE spread Gram-negative is serious public health threat, as it can critically limit types drugs be used treat infected patients. In particular, carbapenem-resistant members family responsible for significant growing burden morbidity mortality. Here, report underlying evolution several isolates Center (NIH CC). Our ability track occurred was dependent accurate annotation elements plasmids, which greatly aided access long-read DNA sequencing data knowledge mechanisms. Mobile such integrons strongly associated rapid Understanding consequences actions allowed us establish unambiguous relationships between set.