Expression profiling in a mammalian host reveals the strong induction of genes encoding LysM domain-containing proteins in Enterococcus faecium

Abstract

Enterococcus faecium is an important health care-associated pathogen that is difficult to treat due to the high level of antibiotic resistance of clinical isolates. The identification of new potential therapeutic targets or vaccination strategies is therefore urgently needed. In this regard, we carried out a transcriptomic analysis of the E. faecium vancomycin-resistant strain AUS0004, comparing the gene expression of bacteria grown under laboratory conditions and bacteria isolated from an infection site. This analysis highlighted more than 360 genes potentially induced under infection conditions. Owing to their expression profiles, four LysM domain-containing proteins were characterized in more detail. The EFAU004_01059, 1150 and 494 proteins are highly homologous, whereas EFAU004_01209 has a unique domain-architecture and sequence. The analysis of corresponding mutants showed that all LysM proteins played relevant roles in the infection process of E. faecium in mice. The EFAU004_01209 mutant also displayed profound morphological modifications, suggesting it has a role in cell wall synthesis or cell division. Furthermore, the adhesion to kidney cells and growth of the mutant was affected in human urine. All these phenotypes and the surface exposure of EFAU004_01209 identify this protein as an interesting new drug target in E. faecium.

Use of Cell Envelope Targeting Antibiotics and Antimicrobial Agents as a Powerful Tool to Select for Lactic Acid Bacteria Strains With Improved Texturizing Ability in Milk Fermentations

“…Only the first two of these five genes have previously been associated with vancomycin resistance and texturizing properties; the PBP1A family penicillin-binding protein and LysM peptidoglycan-binding domain-containing protein. Both proteins are involved in cell wall biosynthesis and are induced in the vancomycin resistant Enterococcus faecium strain AUS0004 ( Cacaci et al, 2018 ). Furthermore, disruption of the gene encoding penicillin-binding protein 2b was resulted in reduction of EPS production in S. thermophilu s Sfi6 ( Stingele and Mollet, 1996 ).…”

Gene Duplications in the Genomes of Staphylococci and Enterococci

“…Expression of GlsB proteins has been associated with virulence and bile salt stress (Choudhury et al, 2011;Zhang et al, 2013a). Proteins containing a LysM domain have been shown to be induced under infection conditions of a mammalian host (Cacaci et al, 2018). Although the proteins of the lactose/cellobiose PTS system IIA and IIB have not been hitherto described as relevant elements in E. faecium virulence, the relevance of the PTS system for the ability of E. faecium to colonize the host has been previously reported.…”

Advances and Prospects in Vaccine Development against Enterococci

“…On the other hand, a peptidoglycan-binding protein LysM, a d-alanyl-d-alanine carboxypeptidase (DdcP), a peptidyl-prolyl cis-trans isomerase (PpiC), and a low-affinity penicillin-binding protein 5 (PBP5) are surface-exposed proteins, which are associated with peptidoglycan [107]. Although the function of these proteins has not been completely elucidated, these four proteins have been associated with resistance to ampicillin and high salt concentrations, and there are indications for their involvement in bacterial virulence and infection [33,[108][109][110][111]. Finally, several of these proteins have been identified in membrane vesicles (MVs) of E. faecium, conferring immunogenic properties to the MVs and making them interesting vaccine candidates [107].…”