Human Serum Induces Streptococcal C5a Peptidase Expression

Abstract

Streptococcus agalactiae is a major pathogen in humans and animals. Virulence factors are often associated with mobile genetic elements, and their expression can be modulated by host factors. S. agalactiae harbors the genes for C5a peptidase (scpB) and Lmb on a composite transposon structure which is absent in many bovine isolates. To investigate whether these genes participate in the adaptation to human hosts, we determined the influence of human and bovine serum on the promoter activity of scpB and lmb by using fluorescence-activated cell sorter analysis. Culture in the presence of 1 to 50% human serum resulted in a dose-dependent induction of reporter gene activity for scpB but not lmb. Reporter gene activity was, however, unchanged following growth in fetal calf serum. Interestingly, a bovine strain did not display any induction of scpB by either bovine or human serum. Reverse transcription-PCR analysis was used to confirm differential induction of scpB in S. agalactiae and showed a similar induction of the Streptococcus pyogenes C5a peptidase gene scpA by human but not bovine serum. The specific induction of the streptococcal C5a peptidase by human serum corresponds to the absence of scpB in many bovine S. agalactiae isolates and underlines the importance of this virulence factor for human infections.Streptococcus agalactiae (group B streptococci [GBS]) was initially identified as the causative agent of bovine mastitis. It later emerged as the major pathogen of bacterial sepsis and meningitis in neonates and has recently been recognized as an increasingly common cause of invasive disease in immunocompromised patients (16). Like other bacterial pathogens, e.g., Streptococcus pneumoniae (27), Enterococcus faecalis (33), and Streptococcus mutans (38), it has the ability to survive and multiply in various anatomical niches and body fluids of the host, including serum, which requires the expression and coordinate regulation of multiple pathogenicity factors.Genes encoding virulence factors are often associated with mobile genetic elements and controlled by complex regulatory networks (13). The C5a peptidase of S. agalactiae is a surfaceassociated serine protease that plays an important role in virulence of S. agalactiae (6,11,12). The structure of this protein has recently been solved (9). It cleaves the chemotactic complement component C5a (4, 20, 39), binds to fibronectin, and contributes to cellular invasion (1, 11). Following the identification of the gene in Streptococcus pyogenes (44, 45), a nearly identical gene was found in S. agalactiae (12). Together with the detection of flanking mobile genetic elements, the finding suggests horizontal gene transfer of the C5a peptidase gene among pyogenic streptococci (8,17). Interestingly, all human but only some bovine S. agalactiae isolates possess the scpB gene (14, 17). Genetic polymorphisms alter the functional activity of C5a peptidase (5) but do not affect its ability to bind fibronectin (40). Overall, its conserved nucleotide sequence in several ␤-hemolytic ...

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Procession to Pediatric Bacteremia and Sepsis: Covert Operations and Failures in Diplomacy

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Virulence Gene Pool Detected in Bovine Group C Streptococcus dysgalactiae subsp. dysgalactiae Isolates by Use of a Group A S. pyogenes Virulence Microarray

“…equisimilis: lbp (encoding the adhesion Lmb, a laminin-binding protein) (62), ska (encoding the plasminogen-activating Skastreptokinase A protein) (37), slo (encoding the cytolytic streptolysin O toxin) (54), emm (encoding the M protein), as well as scpA (encoding a C5a peptidase), with the latter two genes acting on the complement pathway of the host, inhibiting bacterial opsonization and phagocytosis (8,20). Both the lbp and scpA genes have been found in human GBS isolates and are usually absent in bovine GBS isolates (14). These latter two genes and also ska are known to be carried by a bovine pathogen, S. uberis, although Lmb is not required for the attachment of S. uberis to host epithelial cells, and the Ska locus is devoid of plasminogen activator coding sequences (70).…”