PBP4 Mediates β-Lactam Resistance by Altered Function

Som S Chatterjee; Liang Chen; Aubre Gilbert; Thaina M da Costa; Vinod Nair; Sandip K Datta; Barry N Kreiswirth; Henry F Chambers

doi:10.1128/AAC.00932-17

PBP4 Mediates β-Lactam Resistance by Altered Function

Antimicrob Agents Chemother. 2017 Oct 24;61(11):e00932-17. doi: 10.1128/AAC.00932-17. Print 2017 Nov.

Authors

Som S Chatterjee¹, Liang Chen², Aubre Gilbert³, Thaina M da Costa³, Vinod Nair⁴, Sandip K Datta⁵, Barry N Kreiswirth², Henry F Chambers³

Affiliations

¹ Division of HIV/AIDS, Infectious Diseases and Global Health, Department of Medicine, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA som.chatterjee@ucsf.edu.
² Public Health Research Institute Tuberculosis Center, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
³ Division of HIV/AIDS, Infectious Diseases and Global Health, Department of Medicine, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.
⁴ Microscopy Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
⁵ Bacterial Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Abstract

Penicillin binding protein 4 (PBP4) can provide high-level β-lactam resistance in Staphylococcus aureus A series of missense and promoter mutations associated with pbp4 were detected in strains that displayed high-level resistance. We show here that the missense mutations facilitate the β-lactam resistance mediated by PBP4 and the promoter mutations lead to overexpression of pbp4 Our results also suggest a cooperative interplay among PBPs for β-lactam resistance.

Keywords: PBP4; Staphylococcus aureus; β-lactam resistance.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

MeSH terms

Anti-Bacterial Agents / pharmacology
Genome, Bacterial / genetics
Mutation, Missense / genetics
Penicillin-Binding Proteins / biosynthesis
Penicillin-Binding Proteins / genetics*
Penicillins / metabolism
Penicillins / pharmacology
Promoter Regions, Genetic / genetics*
Staphylococcus aureus / drug effects*
Staphylococcus aureus / genetics*
beta-Lactam Resistance / genetics*

Substances

Anti-Bacterial Agents
Penicillin-Binding Proteins
Penicillins

Grants and funding

R01 AI100291/AI/NIAID NIH HHS/United States