Penicillin binding protein 4: an emerging Staphylococcus aureus therapeutic target
- 1Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
- 2Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, United States
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.
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BibTeX
@article{gondil2026penicillin,
title = {{Penicillin binding protein 4: an emerging Staphylococcus aureus therapeutic target}},
author = {Vijay Singh Gondil and Monica A. Stefaniak and Christian Melander and Paul M. Dunman},
journal = {Frontiers in Cellular and Infection Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1940058},
url = {https://doi.org/10.3389/fcimb.2026.1940058},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Penicillin binding protein 4: an emerging Staphylococcus aureus therapeutic target
AU - Vijay Singh Gondil
AU - Monica A. Stefaniak
AU - Christian Melander
AU - Paul M. Dunman
PY - 2026
DA - 2026/10/22
JO - Frontiers in Cellular and Infection Microbiology
DO - 10.3389/fcimb.2026.1940058
UR - https://doi.org/10.3389/fcimb.2026.1940058
AB - 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.
SN - 2235-2988
ER -