Characterization of Posttranslationally Modified Multidrug Efflux Pumps Reveals an Unexpected Link between Glycosylation and Antimicrobial Resistance.

MBio
Sherif AbouelhadidBrendan W Wren

Abstract

The substantial rise in multidrug-resistant bacterial infections is a current global imperative. Cumulative efforts to characterize antimicrobial resistance in bacteria has demonstrated the spread of six families of multidrug efflux pumps, of which resistance-nodulation-cell division (RND) is the major mechanism of multidrug resistance in Gram-negative bacteria. RND is composed of a tripartite protein assembly and confers resistance to a range of unrelated compounds. In the major enteric pathogen Campylobacter jejuni, the three protein components of RND are posttranslationally modified with N-linked glycans. The direct role of N-linked glycans in C. jejuni and other bacteria has long been elusive. Here, we present the first detailed account of the role of N-linked glycans and the link between N-glycosylation and antimicrobial resistance in C. jejuni We demonstrate the multifunctional role of N-linked glycans in enhancing protein thermostability, stabilizing protein complexes and the promotion of protein-protein interaction, thus mediating antimicrobial resistance via enhancing multidrug efflux pump activity. This affirms that glycosylation is critical for multidrug efflux pump assembly. We present a generalized strategy that co...Continue Reading

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Citations

Dec 3, 2020·Nature Reviews. Microbiology·Andrea Du Toit
Feb 23, 2021·Frontiers in Cellular and Infection Microbiology·Abdi ElmiOzan Gundogdu
Aug 11, 2021·Biochemical Society Transactions·Lok ManStuart J Cordwell
Oct 4, 2021·Microbial Cell Factories·Marta MauriUNKNOWN Glycoengineering of Veterinary Vaccines Consortium

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Methods Mentioned

BETA
glycosylation
circular dichroism
chip
chips
PCR
reversed-phase chromatography

Software Mentioned

TASSER
Sequest
BESTSEL
CLUSTAL Omega
BIAevaluation
Proteome Discoverer
Mascot
Image

Related Concepts

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Campylobacteriosis (ASM)

Campylobacteriosis is caused by the bacteria Campylobacter jejuni and is a common cause of gastroenteritis in humans. Discover the latest research on Campylobacteriosis here.