A Collagen-Binding Adhesin, Acb, and Ten Other Putative MSCRAMM and Pilus Family Proteins of Streptococcus gallolyticus subsp. gallolyticus ( Streptococcus bovis Group, Biotype I)

Abstract

Members of the Streptococcus bovis group are important causes of endocarditis. However, factors associated with their pathogenicity, such as adhesins, remain uncharacterized. We recently demonstrated that endocarditis-derived Streptococcus gallolyticus subsp. gallolyticus isolates frequently adhere to extracellular matrix (ECM) proteins. Here, we generated a draft genome sequence of an ECM protein-adherent S. gallolyticus subsp. gallolyticus strain and found, by genome-wide analyses, 11 predicted LPXTG-type cell wall-anchored proteins with characteristics of MSCRAMMs, including a modular architecture of domains predicted to adopt immunoglobulin (Ig)-like folding. A recombinant segment of one of these, Acb, showed high-affinity binding to immobilized collagen, and cell surface expression of Acb correlated with the presence of acb and collagen adherence of isolates. Three of the 11 proteins have similarities to major pilus subunits and are organized in separate clusters, each including a second Ig-fold-containing MSCRAMM and a class C sortase, suggesting that the sequenced strain encodes three distinct types of pili. Reverse transcription-PCR demonstrated that all three genes of one cluster, acb-sbs7-srtC1, are cotranscribed, consistent with pilus operons of other grampositive bacteria. Further analysis detected expression of all 11 genes in cells grown to mid to late exponential growth phases. Wide distribution of 9 of the 11 genes was observed among S. gallolyticus subsp. gallolyticus isolates with fewer genes present in other S. bovis group species/subspecies. The high prevalence of genes encoding putative MSCRAMMs and pili, including a collagen-binding MSCRAMM, among S. gallolyticus subsp. gallolyticus isolates may play an important role in the predominance of this subspecies in S. bovis endocarditis.Members of the Streptococcus bovis group have long been regarded as opportunistic pathogens and are important causes of endocarditis in humans. These organisms are the most frequently encountered clinical isolates among group D streptococci and the second-most important streptococcal cause of endocarditis after "oral streptococci" (4, 15, 55) which, however, are now classified into many different species and even different genera (16, 28). S. bovis group isolates are considered to be commensals in the intestinal tract, but they have been found only in ϳ2.5% to 15% of the human population (9,24,38,58). Surprisingly, there is a clear correlation-for unknown reasons-between the isolation of S. bovis group organisms as the causative agent of endocarditis and the presence of cancerous lesions and polyps in the intestinal tracts of patients (3,20,24,57), with the first suggestion of this association dating back to 1951 (36). Among patients with carcinoma of the colon, an increased S. bovis carriage rate of 56% was found (24). Whether this increased occurrence is a cause or effect of colon cancer is unclear. However, the association of S. bovis bacteremia or endocarditis with colon cancer raises the intriguing hypothesis...

Genome Sequence ofStreptococcus gallolyticus: Insights into Its Adaptation to the Bovine Rumen and Its Ability To Cause Endocarditis

“…In S. gallolyticus UCN34, two of these pilus operons express a protein similar to collagen binding proteins (Gallo_1570 and Gallo_2179), predicted to be adhesins. Similarly, it was recently described for S. gallolyticus strain TX20005 that it encodes three pilus operons and also collagen binding proteins (54). The locus gallo_2179-2177 is identical to the acb locus of strain TX20005, and the locus gallo_2040-2038 is identical to the sbs15 locus.…”

“…S. gallolyticus isolates responsible for endocarditis exhibited heterogeneous patterns of adherence to extracellular matrix (ECM) proteins, which suggests that they produce different surface components (55). Recently, a collagen binding adhesin together with 10 putative ECM binding proteins were identified in the draft genome sequence of a human isolate of S. gallolyticus (54).…”

Development and Application of a Multilocus Sequence Typing Scheme for Streptococcus gallolyticus subsp. gallolyticus

“…gallolyticus subsp. gallolyticus, a commensal of the gastrointestinal tract, is found in 2.5 to 15% of healthy humans (2). The organism can also act as a pathogen.…”

Streptococcus bovis/gallolyticus Induce the Development of Colorectal Cancer

“…However, their ability to adhere to and colonize host tissues is largely unknown. It was found that S. bovis/gallolyticus bacteria possess collagenbinding proteins and pili that are responsible for adhesion to colorectal mucosa as well as to endocardium (Sillanpaa et al, 2009). On the other hand, another study (Boleij et al, 2009b) found a histone-like protein A on the surface of S. bovis/gallolyticus able to bind heparan sulfate proteoglycans at the colon tumor cell surface during the first stages of infection; this cell surface protein in S. gallolyticus acts as one of the main heparin-binding proteins that is largely responsible for bacteria selective adhesive potential as well as entry to the blood circulation.…”