Characterization of a bovine lactoferrin binding protein of Streptococcus uberis

Moshynskyy, Igor; Jiang, Min; Fontaine, Michaël C.; Perez-Casal, José; Babiuk, Lorne A.; Potter, Andrew

doi:10.1016/s0882-4010(03)00150-5

Cited by 31 publications

(28 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This M-like protein gene is identical to the recently published simA gene sequences from S. iniae strains QMA0076 and QMA0131 [29]. BLAST (tblastn) analysis groups SiMA closest to the S. uberis lactoferrin binding protein, Lbp (32% identity, 49% positive) [30] and the S. dysgalactiae subsp. dysgalactiae (GCS) M-like protein, DemA (31% identity, 51% positive) [31], though SiMA has near comparable similarity to a number of other streptococcal M family proteins (Fig.…”

Section: Resultssupporting

confidence: 67%

Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development

et al. 2008

View full text Add to dashboard Cite

Background Streptococcus iniae is a significant pathogen in finfish aquaculture, though knowledge of virulence determinants is lacking. Through pyrosequencing of the S. iniae genome we have identified two gene homologues to classical surface-anchored streptococcal virulence factors: M-like protein (simA) and C5a peptidase (scpI).Methodology/Principal Findings S. iniae possesses a Mga-like locus containing simA and a divergently transcribed putative mga-like regulatory gene, mgx. In contrast to the Mga locus of group A Streptococcus (GAS, S. pyogenes), scpI is located distally in the chromosome. Comparative sequence analysis of the Mgx locus revealed only one significant variant, a strain with an insertion frameshift mutation in simA and a deletion mutation in a region downstream of mgx, generating an ORF which may encode a second putative mga-like gene, mgx2. Allelic exchange mutagenesis of simA and scpI was employed to investigate the potential role of these genes in S. iniae virulence. Our hybrid striped bass (HSB) and zebrafish models of infection revealed that M-like protein contributes significantly to S. iniae pathogenesis whereas C5a peptidase-like protein does not. Further, in vitro cell-based analyses indicate that SiMA, like other M family proteins, contributes to cellular adherence and invasion and provides resistance to phagocytic killing. Attenuation in our virulence models was also observed in the S. iniae isolate possessing a natural simA mutation. Vaccination of HSB with the ΔsimA mutant provided 100% protection against subsequent challenge with a lethal dose of wild-type (WT) S. iniae after 1,400 degree days, and shows promise as a target for live attenuated vaccine development.Conclusions/SignificanceAnalysis of M-like protein and C5a peptidase through allelic replacement revealed that M-like protein plays a significant role in S. iniae virulence, and the Mga-like locus, which may regulate expression of this gene, has an unusual arrangement. The M-like protein mutant created in this research holds promise as live-attenuated vaccine.

show abstract

Section: Resultssupporting

confidence: 67%

Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The protein encoded by sub0145 has previously been identified as a possible virulence determinant of S. uberis and at least one allelic variant has been shown to bind bovine lactoferrin [28]. The concentration of this iron-chelating compound increases in the mammary gland during infection [17] however whilst iron limitation is known to have an anti-microbial effect on some bacteria, it appears to have little effect on the growth of S. uberis [9, 36].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2010

View full text Add to dashboard Cite

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.

show abstract

“…The ability to bind lactoferrin or use it as a source of iron for growth has been demonstrated in a variety of different bacterial species (Redhead et al 1987;Tryon and Baseman 1987;Naidu et al 1990Naidu et al , 1991Naidu et al , 1992Tigyi et al 1992;Staggs et al 1994;Alugupalli et al 1995;Dhaenens et al 1997;Moshynskyy et al 2003) but these systems are unrelated to the lactoferrin receptors in the Neisseriaceae and Moraxellaceae families and their role in iron acquisition are not well established.…”

mentioning

confidence: 99%

The lactoferrin receptor complex in gram negative bacteria

Beddek

Schryvers

2010

Biometals

View full text Add to dashboard Cite

Bacteria that inhabit the respiratory and genitourinary tracts of mammals encounter an iron-deficient environment on the mucosal surface where iron is complexed by the host iron-binding proteins transferrin and lactoferrin. Lactoferrin is also present in high concentrations at sites of inflammation where the cationic anti-microbial peptide lactoferricin is produced by proteolysis of lactoferrin. Several members of the Neisseriaceae and Moraxellaceae families express surface receptors, capable of specifically binding host lactoferrin and extracting the iron from lactoferrin as a source of iron for growth. The receptor is comprised of an integral outer membrane protein, lactoferrin binding protein A (LbpA), and a largely exposed surface lipoprotein, lactoferrin binding protein B (LbpB). LbpA is essential for mediating growth using lactoferrin as a sole iron source whereas LbpB only plays a facilitating role. LbpB, with the presence of a large tract of negatively charged residues, appears to protect the bacterial cell from the bactericidal effects of the lactoferricin. The lactoferrin receptors in these species appear to be essential for survival and thus may serve as potential vaccine targets.

show abstract

Characterization of a bovine lactoferrin binding protein of Streptococcus uberis

Cited by 31 publications

References 41 publications

Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development

Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development

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

The lactoferrin receptor complex in gram negative bacteria

Contact Info

Product

Resources

About