Genome sequence of Streptococcus gallolyticus: insights into its adaptation to the bovine rumen and its ability to cause endocarditis

Abstract

Streptococcus gallolyticus (formerly known as Streptococcus bovis biotype I) is an increasing cause of endocarditis among streptococci and frequently associated with colon cancer. S. gallolyticus is part of the rumen flora but also a cause of disease in ruminants as well as in birds. Here we report the complete nucleotide sequence of strain UCN34, responsible for endocarditis in a patient also suffering from colon cancer. Analysis of the 2,239 proteins encoded by its 2,350-kb-long genome revealed unique features among streptococci, probably related to its adaptation to the rumen environment and its capacity to cause endocarditis. S. gallolyticus has the capacity to use a broad range of carbohydrates of plant origin, in particular to degrade polysaccharides derived from the plant cell wall. Its genome encodes a large repertoire of transporters and catalytic activities, like tannase, phenolic compounds decarboxylase, and bile salt hydrolase, that should contribute to the detoxification of the gut environment. Furthermore, S. gallolyticus synthesizes all 20 amino acids and more vitamins than any other sequenced Streptococcus species. Many of the genes encoding these specific functions were likely acquired by lateral gene transfer from other bacterial species present in the rumen. The surface properties of strain UCN34 may also contribute to its virulence. A polysaccharide capsule might be implicated in resistance to innate immunity defenses, and glucan mucopolysaccharides, three types of pili, and collagen binding proteins may play a role in adhesion to tissues in the course of endocarditis.

FIG. 1.

Circular genome map of S. gallolyticus UCN34 showing the position and orientation of predicted genes. From outside to inside, circle 1, protein coding genes on the + and − strands, with genes with nonstreptococcal best BlastP hit in black; circle 2, G/C bias (G+C/G−C); circle 3: G+C content, with <30.9% G+C in yellow, between 30.9% and 44.4% G+C in orange, and with >44.4% G+C in red; circle 4, stable RNA coding genes. Numbers in blue on the external circle correspond to genes discussed in the text: polysaccharide utilization (1, gallo_0112; 2, gallo_0162; 3, gallo_0189; 4, gallo_0330; 5, gallo_0757; 6, gallo_1462; 7, gallo_1577-1578; 8, amyE), vitamin biosynthesis (9, panBCD; 10, panE; 11, ribDEAH; 12, bioBDY), polysaccharide biosynthesis (13, gallo_0364-0367; 14, cps operon; 15, gallo_1052-1057), pilus operons (16, gallo_1568-1570; 17, gallo_2040-2038; 18, gallo_2179-2177), and detoxification (19, bsh; 20, gallo_0906; 21, tanA; 22, gallo_1609; 23, gallo_2106). The scale in kb is indicated outside the genome, with the predicted origin of replication being at position 0.

FIG. 2.

Distribution of best BlastP hits. Blue, pyogenic streptococci; purple, viridans group streptococci; green, other streptococci; orange, other Firmicutes; black, others.

FIG. 3.

Loci involved in the synthesis of extracellular polysaccharides. (A) The 12-gene operon responsible for the synthesis of the capsular polysaccharides. cpsA (gallo_0944) encodes a regulator of the LytR family, cpsE (gallo_0948) an undecaprenyl-phosphate glycosyl-1-phosphate transferase, cpsF (gallo_0949) a rhamosyl transferase, cpsH (gallo_0950) a polymerase, cpsI and cpsJ (gallo_0951) sugar transferases, cpsK (gallo_0953) the transporter or flippase, cpsL (gallo_0954) a CDP-glycerol:polyglycerol phosphate glycero-phosphotransferase, and cpsM (gallo_0955) a glycerol-3-phosphate cytidylyltransferase. The color of the arrow indicates the species encoding the best BlastP hit: red, S. pneumoniae; blue, S. agalactiae; orange, S. thermophilus; and black, other. (B) Putative locus involved in mucopolysaccharide biosynthesis. Genes encoding glycosytransferases are in blue and regulators in red. (C) S. gallolyticus UCN34 grown on TH medium supplemented with 1% glucose or sucrose. (D) Operon putatively involved in the biosynthesis of a hemicellulose-like molecule. gallo_0364 encodes a putative diguanylate cyclase, gallo_0365 and gallo_0366 encode two putative glycosyl transferases, and gallo_0367 encodes a 12-transmembrane domain protein.

FIG. 4.

Phylogenetic relationship of sortase A protein sequences with representative sequences from Firmicutes. The three sortase A encoded by strain UCN34 are boxed. Gallo_0299 is expressed by TnGallo1 and Gallo_1651 by ICESgal1. SrtA is the S. gallolyticus housekeeping sortase encoded by the srtA gene located downstream of the gyrA gene. The scale bar represents 0.2 substitutions per site. The numbers at the branches are posterior probabilities indicating the support for the branch. GI numbers for sequences are given in parentheses.