Inhibitors of bacterial H 2 S biogenesis targeting antibiotic resistance and tolerance
Abstract
Persister cells, which are found in abundance in biofilms, adopt a quiescent state and survive antimicrobial treatments, seeding disease recurrence and incubating new resistance mutations. Building on work implicating the reactive small-molecule hydrogen sulfide in bacterial defense against antibiotics, Shatalin et al. conducted a structure-based screen for inhibitors of a bacterial hydrogen sulfide–producing enzyme and found a group of inhibitors that act through an allosteric mechanism (see the Perspective by Mah). These inhibitors potentiated bactericidal antibiotics in vitro and in mouse infection models. They also suppressed persister bacteria and disrupted biofilm formation. This strategy of taking out persister cells may be promising for treating recalcitrant infections and holding the line against drug-resistant bacteria.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 11, 2021
- Source ID
- 10.1126/science.abd8377
Entities
People
- Abhishek Kaushik
- Alexander Mironov
- Alexander Serganov
- Alla Peselis
- Ashok Nuthanakanti
- Bibhusita Pani
- Dmitri Rebatchouk
- Dmitry Shishov
- Elena Shatalina
- Evgeny Nudler
- Ilya Shamovsky
- Konstantin Shatalin
- Mirna Lechpammer
- Nikita Vasilyev
- Peter Fedichev
Organizations
- Engelhardt Institute of Molecular Biology
- Grossman School of Medicine
- Howard Hughes Medical Institute
- New York University
- United States Department of Defense