Resistance to nonribosomal peptide antibiotics mediated by D-stereospecific peptidases.

Abstract:

:Nonribosomal peptide antibiotics, including polymyxin, vancomycin, and teixobactin, most of which contain D-amino acids, are highly effective against multidrug-resistant bacteria. However, overusing antibiotics while ignoring the risk of resistance arising has inexorably led to widespread emergence of resistant bacteria. Therefore, elucidation of the emerging mechanisms of resistance to nonribosomal peptide antibiotics is critical to their implementation. Here we describe a networking-associated genome-mining platform for linking biosynthetic building blocks to resistance components associated with biosynthetic gene clusters. By applying this approach to 5,585 complete bacterial genomes spanning the entire domain of bacteria, with subsequent chemical and enzymatic analyses, we demonstrate a mechanism of resistance toward nonribosomal peptide antibiotics that is based on hydrolytic cleavage by D-stereospecific peptidases. Our finding reveals both the widespread distribution and broad-spectrum resistance potential of D-stereospecific peptidases, providing a potential early indicator of antibiotic resistance to nonribosomal peptide antibiotics.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Li YX,Zhong Z,Hou P,Zhang WP,Qian PY

doi

10.1038/s41589-018-0009-4

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

381-387

issue

4

eissn

1552-4450

issn

1552-4469

pii

10.1038/s41589-018-0009-4

journal_volume

14

pub_type

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