Sortase anchored proteins ofStreptococcus uberisplay major roles in the pathogenesis of bovine mastitis in dairy cattle

Abstract

Streptococcus uberis, strain 0140J, contains a single copy sortase A (srtA), encoding a transamidase capable of covalently anchoring specific proteins to peptidoglycan. Unlike the wild-type, an isogenic mutant carrying an inactivating ISS1 insertion within srtA was only able to infect the bovine mammary gland in a transient fashion. For the first 24 h post challenge, the srtA mutant colonised at a similar rate and number to the wild type strain, but unlike the wild type did not subsequently colonise in higher numbers. Similar levels of host cell infiltration were detected in response to infection with both strains, but only in those mammary quarters infected with the wild type strain were clinical signs of disease evident. Mutants that failed to express individual sortase substrate proteins (sub0135, sub0145, sub0207, sub0241, sub0826, sub0888, sub1095, sub1154, sub1370, and sub1730) were isolated and their virulence determined in the same challenge model. This revealed that mutants lacking sub0145, sub1095 and sub1154 were attenuated in cattle. These data demonstrate that a number of sortase anchored proteins each play a distinct, non-redundant and important role in pathogenesis of S. uberis infection within the lactating bovine mammary gland.

Role of Streptococcus uberis adhesion molecule in the pathogenesis of Streptococcus uberis mastitis

“…Work conducted by others and our research team showed the expression of virulence factors other than SUAM (Fontaine et al, 2002;Leigh et al, 2010;Eagan et al, 2012). These reports raise the concept that pathogenic events leading to S. uberis IMI cannot be attributed only to SUAM.…”

“…Leigh et al (2010) reported a gene for sortase A (srtA) with role in the anchoring of putative virulence proteins to the cell wall and further research resulted on the identification of Vru a gene with regulatory activity on gene expression (Eagan et al, 2011). Although these reports are of great value to understand how S. uberis regulates the expression of surface proteins, they do not provide information about their specific role in the pathogenic process.…”

Comparative genomics and the role of lateral gene transfer in the evolution of bovine adapted Streptococcus agalactiae

“…Proteins with this motif are usually covalently linked to the cell surface and are implicated in pathogen survival within the host (Navarre and Schneewind, 1999; Schneewind et al, 1995). In the case of mastitis caused by S. uberis , experimental challenge studies have demonstrated a role for sortase and sortase anchored proteins in virulence, most of which carry the LPXTG anchoring motive (Leigh et al, 2010). Consequently, each of the four copies of FSL S3-026-S20 may contribute to virulence of the bovine S. agalactiae strain, and given the nature of the repeat sequence, these potential virulence factors may have been exchanged with other bacteria via LGT.…”

Differential Protein Expression in Streptococcus uberis under Planktonic and Biofilm Growth Conditions

“…2c) and decrease in glyC (Ͼ9-fold). Mutation of SUB0145 has recently been shown to impair virulence for the bovine lactating gland (11). In addition to iron, lactoferrin (Lf) is also capable of binding other divalent metal ions (such as manganese, which has been shown to be involved in S. uberis virulence via the mtu operon [20]).…”