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 Bioljournal_title
Nature chemical biologyauthors
Li YX,Zhong Z,Hou P,Zhang WP,Qian PYdoi
10.1038/s41589-018-0009-4subject
Has Abstractpub_date
2018-04-01 00:00:00pages
381-387issue
4eissn
1552-4450issn
1552-4469pii
10.1038/s41589-018-0009-4journal_volume
14pub_type
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