Inhibition of the D-alanine:D-alanyl carrier protein ligase from Bacillus subtilis increases the bacterium's susceptibility to antibiotics that target the cell wall - PubMed (original) (raw)

Inhibition of the D-alanine:D-alanyl carrier protein ligase from Bacillus subtilis increases the bacterium's susceptibility to antibiotics that target the cell wall

Juergen J May et al. FEBS J. 2005 Jun.

Free article

Abstract

The surface charge as well as the electrochemical properties and ligand binding abilities of the Gram-positive cell wall is controlled by the D-alanylation of the lipoteichoic acid. The incorporation of D-Ala into lipoteichoic acid requires the D-alanine:D-alanyl carrier protein ligase (DltA) and the carrier protein (DltC). We have heterologously expressed, purified, and assayed the substrate selectivity of the recombinant proteins DltA with its substrate DltC. We found that apo-DltC is recognized by both endogenous 4'-phosphopantetheinyl transferases AcpS and Sfp. After the biochemical characterization of DltA and DltC, we designed an inhibitor (D-alanylacyl-sulfamoyl-adenosine), which is able to block the D-Ala adenylation by DltA at a K(i) value of 232 nM vitro. We also performed in vivo studies and determined a significant inhibition of growth for different Bacillus subtilis strains when the inhibitor is used in combination with vancomycin.

PubMed Disclaimer

Cited by

The antibiotic CJ-15,801 is an antimetabolite that hijacks and then inhibits CoA biosynthesis.
van der Westhuyzen R, Hammons JC, Meier JL, Dahesh S, Moolman WJ, Pelly SC, Nizet V, Burkart MD, Strauss E. van der Westhuyzen R, et al. Chem Biol. 2012 May 25;19(5):559-71. doi: 10.1016/j.chembiol.2012.03.013. Chem Biol. 2012. PMID: 22633408 Free PMC article.
The absence of surface D-alanylation, localized on lipoteichoic acid, impacts the Clostridioides difficile way of life and antibiotic resistance.
Lacotte PA, Denis-Quanquin S, Chatonnat E, Le Bris J, Leparfait D, Lequeux T, Martin-Verstraete I, Candela T. Lacotte PA, et al. Front Microbiol. 2023 Oct 30;14:1267662. doi: 10.3389/fmicb.2023.1267662. eCollection 2023. Front Microbiol. 2023. PMID: 37965542 Free PMC article.
Resistance Mechanisms to Antimicrobial Peptides in Gram-Positive Bacteria.
Assoni L, Milani B, Carvalho MR, Nepomuceno LN, Waz NT, Guerra MES, Converso TR, Darrieux M. Assoni L, et al. Front Microbiol. 2020 Oct 21;11:593215. doi: 10.3389/fmicb.2020.593215. eCollection 2020. Front Microbiol. 2020. PMID: 33193264 Free PMC article. Review.
Breaking down the cell wall: Still an attractive antibacterial strategy.
Zhou J, Cai Y, Liu Y, An H, Deng K, Ashraf MA, Zou L, Wang J. Zhou J, et al. Front Microbiol. 2022 Sep 23;13:952633. doi: 10.3389/fmicb.2022.952633. eCollection 2022. Front Microbiol. 2022. PMID: 36212892 Free PMC article. Review.
Methicillin resistance in Staphylococcus aureus requires glycosylated wall teichoic acids.
Brown S, Xia G, Luhachack LG, Campbell J, Meredith TC, Chen C, Winstel V, Gekeler C, Irazoqui JE, Peschel A, Walker S. Brown S, et al. Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):18909-14. doi: 10.1073/pnas.1209126109. Epub 2012 Oct 1. Proc Natl Acad Sci U S A. 2012. PMID: 23027967 Free PMC article.

Inhibition of the D-alanine:D-alanyl carrier protein ligase from Bacillus subtilis increases the bacterium's susceptibility to antibiotics that target the cell wall - PubMed (original) (raw)