The multiple antibiotic resistance operon of enteric bacteria controls DNA repair and outer membrane integrity

Prateek Sharma, James Haycocks, Alistair Middlemiss, Rachel Kettles, Laura Sellars, Vito Ricci, Laura Piddock, David Grainger

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)
164 Downloads (Pure)

Abstract

The multiple antibiotic resistance (mar) operon of Escherichia coli is a paradigm for chromosomally encoded antibiotic resistance in enteric bacteria. The locus is recognised for its ability to modulate efflux pump and porin expression via two encoded transcription factors, MarR and MarA. Here we map binding of these regulators across the E. coli genome and identify an extensive mar regulon. Most notably, MarA activates expression of genes required for DNA repair and lipid trafficking. Consequently, the mar locus reduces quinolone-induced DNA damage and the ability of tetracyclines to traverse the outer membrane. These previously unrecognised mar pathways reside within a core regulon, shared by most enteric bacteria. Hence, we provide a framework for understanding multidrug resistance, mediated by analogous systems, across the Enterobacteriaceae.
Original languageEnglish
Article number1444 (2017)
JournalNature Communications
Volume8
Issue number1
Early online date13 Nov 2017
DOIs
Publication statusE-pub ahead of print - 13 Nov 2017

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