Work

Penicillin binding protein 4: an emerging Staphylococcus aureus therapeutic target

Year: 2026

Type: review

Abstract: Staphylococcus aureus penicillin-binding protein 4 (PBP4) is a non-essential, low-molecular-weight transpeptidase that contributes to peptidoglycan maintenance under conventional laboratory growth conditions. Several recent studies have suggested that the protein’s cellular functions have far-reaching consequences, directly affecting S. aureus success as a human pathogen. Herein, we review recent work implicating PBP4 as a modulator of a noncanonical PBP2A-independent methicillin-resistant S. aureus (MRSA) phenotype that extends to the most recently developed fifth-generation cephalosporins. Furthermore, we review emerging studies indicating that PBP4 is a previously unappreciated virulence factor that governs an essential step in osteomyelitis pathogenesis, namely the invasion of osteocyte lacuna-canalicular networks (OLCNs). Given the protein’s involvement in these two disease-related processes, we discuss PBP4’s potential as a non-traditional antimicrobial therapeutic target.

Source: Frontiers in Cellular and Infection Microbiology

DOI: 10.3389/fcimb.2026.1940058

Authors: Vijay Singh Gondil, Monica A. Stefaniak, Christian Melander, Paul M. Dunman

Institutions: University of Rochester Medicine, University of Rochester, University of Notre Dame

Language: English

Topic: Antimicrobial Resistance in Staphylococcus

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801