AUTHOR=Song Xin , Li Fengjiao , Zhang Mingshu , Xia Yongjun , Ai Lianzhong , Wang Guangqiang 

TITLE=Effect of D-Ala-Ended Peptidoglycan Precursors on the Immune Regulation of Lactobacillus plantarum Strains

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.825825

DOI=10.3389/fimmu.2021.825825

ISSN=1664-3224

ABSTRACT=<p>The resistance of <italic>Lactobacillus plantarum</italic> to vancomycin depends on its peptidoglycan composition. Vancomycin has poor binding affinity with peptidoglycan precursors ending in D-alanyl-D-lactate (D-Ala-D-Lac) but binds strongly to peptidoglycan precursors ending in D-alanyl-D-alanine (D-Ala-D-Ala), resulting in resistance and sensitivity, respectively. The ligase Ddl, which generates D-Ala-D-Lac or D-Ala-D-Ala incorporated into the peptidoglycan precursor chain, is responsible for this specificity. To study the effect of peptidoglycan precursors on immunity, we constructed several strains of <italic>L. plantarum</italic> expressing the <italic>ddl</italic> gene of <italic>Lactococcus lactis</italic> to change their peptidoglycan precursors. The change in the termini of the peptidoglycan precursors was determined by the sensitivity of the strains to vancomycin. The overexpression of <italic>ddl</italic> increased the susceptibility of the strains to vancomycin. We further explored the regulation of the macrophage inflammatory response pathway by the wild-type and constructed strains, and found that these strains induced the MyD88-dependent TRAF6/MAPK pathway, and the increase in D-Ala <italic>L. plantarum</italic> peptidoglycan precursors increased the secretion of the inflammatory factors IL-6, IL-1β and TNF-α. These results indicate that D-Ala-ended peptidoglycan precursors play a central role in the variable immunomodulatory ability of <italic>L. plantarum</italic>.</p>