Surface-Exposed Histone-Like Protein A Modulates Adherence of Streptococcus gallolyticus to Colon Adenocarcinoma Cells

Abstract

Streptococcus gallolyticus (formerly known as Streptococcus bovis biotype I) is a low-grade opportunistic pathogen which is considered to be associated with colon cancer. It is thought that colon polyps or tumors are the main portal of entry for this bacterium and that heparan sulfate proteoglycans (HSPGs) at the colon tumor cell surface are involved in bacterial adherence during the first stages of infection. In this study, we have shown that the histone-like protein A (HlpA) of S. gallolyticus is a genuine anchorless bacterial surface protein that binds to lipoteichoic acid (LTA) of the gram-positive cell wall in a growth phase-dependent manner. In addition, HlpA was shown to be one of the major heparin-binding proteins of S. gallolyticus able to bind to the HSPG-expressing colon tumor cell lines HCT116 and HT-29. Strikingly, although wild-type levels of HlpA appeared to contribute to adherence, coating of additional HlpA at the bacterial surface resulted in reduced binding to colon tumor cells. This may be explained by the fact that heparan sulfate and LTA compete for the same binding site in HlpA. Altogether, this study implies that HlpA serves as a fine-tuning factor for bacterial adherence.

An Adhesin-Like Protein, Lam29, fromLactobacillus mucosaeME-340 Binds to Histone H3 and Blood Group Antigens in Human Colonic Mucus

“…In the former case, the binding of surfaceassociated histone-like protein (HlpA) from Streptococcus gallolyticus to colon adenocarcinoma cells 29) and the binding of Hlp/LBP from Mycobacterium leprae to the extracellular matrix, 30) and in the latter case, the adhesion of 987P fimbriae from enterotoxigenic E. coli to histone H1 receptor 23) were reported. This indicates that histone proteins may be important factors in establishing infections by pathogenic bacteria in the human gastrointestinal tract.…”

Genomics, evolution, and molecular epidemiology of the Streptococcus bovis / Streptococcus equinus complex (SBSEC)

“…General adherence characteristics of streptococci were related to histone-like protein A (HlpA), a bacterial surface protein enabling adherence to certain colon tumour cell lines (Boleij et al, 2009), fibrinogen binding factor B (FimB), glucosyltransferase, and pilus subunit PilB (Hinse et al, 2008;Vollmer et al, 2010). FimB and PilB belong to streptococcal adhesins such as FimA, SsaB, ScaA, PsaA and in the case of PilB contribute to the adhesion to endothelial cells and promote phagocyte resistance in group B and other streptococci (Burnette-Curley et al, 1995;Maisey et al, 2007;Maisey et al, 2008).…”

Intestinal Host-Microbiome Interactions

“…Besides the ECM components, also other structures at the epithelial surface may play a role in the initial adhesion to enterocytes. For example, Henry-Stanley et al (2003) reported binding of S. bovis strains to heparan sulfate proteoglycans, which may be mediated by surface-associated HlpA (Boleij et al, 2009). In an in vitro trans-well model containing a differentiated intestinal monolayer, the paracellular translocation efficiency of S. gallolyticus was shown to be significantly higher than that of other S. bovis biotypes.…”