Penicillin-Binding Proteins (PBPs) and Bacterial Cell Wall Elongation Complexes - PubMed

Review

Penicillin-Binding Proteins (PBPs) and Bacterial Cell Wall Elongation Complexes

Mayara M Miyachiro et al. Subcell Biochem. 2019.

Abstract

The bacterial cell wall is the validated target of mainstream antimicrobials such as penicillin and vancomycin. Penicillin and other β-lactams act by targeting Penicillin-Binding Proteins (PBPs), enzymes that play key roles in the biosynthesis of the main component of the cell wall, the peptidoglycan. Despite the spread of resistance towards these drugs, the bacterial cell wall continues to be a major Achilles' heel for microbial survival, and the exploration of the cell wall formation machinery is a vast field of work that can lead to the development of novel exciting therapies. The sheer complexity of the cell wall formation process, however, has created a significant challenge for the study of the macromolecular interactions that regulate peptidoglycan biosynthesis. New developments in genetic and biochemical screens, as well as different aspects of structural biology, have shed new light on the importance of complexes formed by PBPs, notably within the cell wall elongation machinery. This chapter summarizes structural and functional details of PBP complexes involved in the periplasmic and membrane steps of peptidoglycan biosynthesis with a focus on cell wall elongation. These assemblies could represent interesting new targets for the eventual development of original antibacterials.

Keywords: Cell wall elongation; Membrane proteins; Penicillin-Binding proteins (PBPs); Peptidoglycan; Periplasm; Protein complexes.

Similar articles

• Bridging cell wall biosynthesis and bacterial morphogenesis.

  Matteï PJ, Neves D, Dessen A. Matteï PJ, et al. Curr Opin Struct Biol. 2010 Dec;20(6):749-55. doi: 10.1016/j.sbi.2010.09.014. Epub 2010 Oct 26. Curr Opin Struct Biol. 2010. PMID: 21030247 Review.

• Unipolar Peptidoglycan Synthesis in the Rhizobiales Requires an Essential Class A Penicillin-Binding Protein.

  Williams MA, Aliashkevich A, Krol E, Kuru E, Bouchier JM, Rittichier J, Brun YV, VanNieuwenhze MS, Becker A, Cava F, Brown PJB. Williams MA, et al. mBio. 2021 Oct 26;12(5):e0234621. doi: 10.1128/mBio.02346-21. Epub 2021 Sep 21. mBio. 2021. PMID: 34544272 Free PMC article.

• Class A PBPs have a distinct and unique role in the construction of the pneumococcal cell wall.

  Straume D, Piechowiak KW, Olsen S, Stamsås GA, Berg KH, Kjos M, Heggenhougen MV, Alcorlo M, Hermoso JA, Håvarstein LS. Straume D, et al. Proc Natl Acad Sci U S A. 2020 Mar 17;117(11):6129-6138. doi: 10.1073/pnas.1917820117. Epub 2020 Mar 2. Proc Natl Acad Sci U S A. 2020. PMID: 32123104 Free PMC article.

• The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis.

  Sauvage E, Kerff F, Terrak M, Ayala JA, Charlier P. Sauvage E, et al. FEMS Microbiol Rev. 2008 Mar;32(2):234-58. doi: 10.1111/j.1574-6976.2008.00105.x. Epub 2008 Feb 11. FEMS Microbiol Rev. 2008. PMID: 18266856 Review.

• Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases.

  Paradis-Bleau C, Markovski M, Uehara T, Lupoli TJ, Walker S, Kahne DE, Bernhardt TG. Paradis-Bleau C, et al. Cell. 2010 Dec 23;143(7):1110-20. doi: 10.1016/j.cell.2010.11.037. Cell. 2010. PMID: 21183074 Free PMC article.

Cited by

• Bacterial Resistance to Antimicrobial Agents.

  Varela MF, Stephen J, Lekshmi M, Ojha M, Wenzel N, Sanford LM, Hernandez AJ, Parvathi A, Kumar SH. Varela MF, et al. Antibiotics (Basel). 2021 May 17;10(5):593. doi: 10.3390/antibiotics10050593. Antibiotics (Basel). 2021. PMID: 34067579 Free PMC article. Review.

• Enhanced Antimicrobial Activity through Synergistic Effects of Cold Atmospheric Plasma and Plant Secondary Metabolites: Opportunities and Challenges.

  Prasad K, Sasi S, Weerasinghe J, Levchenko I, Bazaka K. Prasad K, et al. Molecules. 2023 Nov 8;28(22):7481. doi: 10.3390/molecules28227481. Molecules. 2023. PMID: 38005203 Free PMC article. Review.

• Live-Cell Profiling of Penicillin-Binding Protein Inhibitors in Escherichia coli MG1655.

  Shirley JD, Nauta KM, Carlson EE. Shirley JD, et al. ACS Infect Dis. 2022 Jul 8;8(7):1241-1252. doi: 10.1021/acsinfecdis.2c00004. Epub 2022 Jun 28. ACS Infect Dis. 2022. PMID: 35763562 Free PMC article.

• Cell wall thickness and the molecular mechanism of heterogeneous vancomycin-intermediate Staphylococcus aureus.

  Cui J, Zhang H, Mo Z, Yu M, Liang Z. Cui J, et al. Lett Appl Microbiol. 2021 May;72(5):604-609. doi: 10.1111/lam.13456. Epub 2021 Feb 15. Lett Appl Microbiol. 2021. PMID: 33539564 Free PMC article.

• Penicillin-binding protein (PBP) inhibitor development: A 10-year chemical perspective.

  Bertonha AF, Silva CCL, Shirakawa KT, Trindade DM, Dessen A. Bertonha AF, et al. Exp Biol Med (Maywood). 2023 Oct;248(19):1657-1670. doi: 10.1177/15353702231208407. Epub 2023 Nov 29. Exp Biol Med (Maywood). 2023. PMID: 38030964 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Springer

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal