DOI: 10.1101/516872Jan 11, 2019Paper

Colistin heteroresistance in Enterobacter cloacae is mediated by PmrAB-independent 4-amino-4-deoxy-l-arabinose addition to lipid A

BioRxiv : the Preprint Server for Biology
Katie N KangJoseph M Boll

Abstract

The Enterobacter cloacae complex (ECC) consists of closely-related, but genetically distinct bacteria commonly associated with the human microbiota. ECC have been increasingly isolated from healthcare-associated infections, demonstrating that these Enterobacteriaceae are emerging nosocomial pathogens. ECC strains can rapidly acquire multidrug resistance to conventional antibiotics. Cationic antimicrobial peptides (CAMPs) have served as therapeutic alternatives because they target the highly conserved lipid A component of the Gram-negative outer membrane to lyse the bacterial cell. Many Gram-negative Enterobacteriaceae fortify their outer membrane with cationic amine-containing moieties to protect from CAMP-inflicted lysis. The PmrAB two-component system (TCS) transcriptionally activates 4-amino-4-deoxy-l-arabinose (l-Ara4N) biosynthesis to result in amine moiety addition to lipid A in many Enterobacteriaceae such as E. coli and Salmonella. In contrast, PmrAB in E. cloacae is dispensable for CAMP resistance. Instead, fitness against CAMPs presents as heteroresistance, or a subpopulation of cells that exhibit clinically significant increases in resistance levels compared to the majority population. We demonstrate that E. cloacae ...Continue Reading

Related Concepts

Antibiotics
Cations
Colistin
Enterobacteriaceae
Escherichia coli
Gram-Negative Bacteria
Lipids
4-amino-4-deoxyarabinose
Cyclophosphamide/Doxorubicin/Methotrexate/Procarbazine Protocol
Antimicrobial Cationic Peptides

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