Penicillin-binding protein 2 (Cutibacterium acnes) (PBP2)

Penicillin-binding protein 2 (PBP2) is an essential enzyme in the bacterium Cutibacterium acnes (formerly Propionibacterium acnes) that is vital for maintaining bacterial cell wall integrity. It functions as a transpeptidase, facilitating the cross-linking of peptidoglycan polymers, which allows the bacterium to survive environmental osmotic pressure [1, 2]. PBP2 is a member of the high-molecular-weight PBP family and serves as a critical target for beta-lactam antibiotics [3]. These drugs, including penicillins and cephalosporins, mimic the D-alanyl-D-alanine substrate and bind covalently to the enzyme's active site, permanently disabling its function [3, 4]. The resulting failure in cell wall synthesis triggers bacterial autolysis and cell death [3]. While C. acnes is a ubiquitous skin commensal, its overproliferation and biofilm formation are central to the pathogenesis of acne vulgaris [5]. Beyond dermatology, the organism is increasingly recognized as a cause of deep-tissue infections, such as prosthetic joint infections and endocarditis, where PBP2 remains a therapeutic focus [5, 6]. Therapeutic challenges include the rising prevalence of antibiotic-resistant C. acnes strains, which may involve structural modifications to PBPs that reduce drug affinity [4, 6]. Understanding the structural biology of PBP2 is therefore essential for developing next-generation antibiotics to combat resistant acne-causing bacteria. Sources: [1] UniProt Consortium. UniProtKB - Q6A7G1 (PBP2_CUTAC). https://www.uniprot.org/uniprotkb/Q6A7G1/entry [2] Scholz, C. F., & Kilian, M. (2016). Int J Syst Evol Microbiol. https://pubmed.ncbi.nlm.nih.gov/27424062/ [3] Bush, K., & Bradford, P. A. (2016). Cold Spring Harb Perspect Med. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971038/ [4] Dréno, B., et al. (2018). JEADV. https://onlinelibrary.wiley.com/doi/full/10.1111/jdv.15043 [5] Achermann, Y., et al. (2014). Clin Microbiol Rev. https://pubmed.ncbi.nlm.nih.gov/25278577/ [6] McDowell, A., et al. (2013). J Clin Microbiol. https://pubmed.ncbi.nlm.nih.gov/22162554/

Other names

PBP2mrdAPeptidoglycan glycosyltransferase/transpeptidase PBP2Propionibacterium acnes PBP2

Covalent inhibition of the transpeptidase domain, preventing peptidoglycan cross-linking and leading to bacterial cell wall lysis.