The expression of a putative exotoxin and an ABC transporter during bovine intramammary infection contributes to the virulence of Staphylococcus aureus

Allard, Marie-Julie; Ster, Céline; Jacob, Christian L.; Scholl, Daniel; Diarra, Moussa S.; Lacasse, P.; Malouin, François

doi:10.1016/j.vetmic.2012.09.029

Cited by 16 publications

(29 citation statements)

References 29 publications

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“…S . aureus ATCC 29213 and its isogenic mutant Δ720 were previously described [19]. Strain Δ720 is an intron insertion mutant of gene vraG that was renamed in this study Δ vraG for clarity.…”

Section: Methodsmentioning

confidence: 99%

“…aureus spa types found in Canadian dairy herds and elsewhere in the world [13,34]. Strain SHY97-3906 ( spa t529) was isolated from a case of clinical bovine mastitis that occurred during the lactation period, and CLJ08-3 ( spa t359) was originally isolated from a cow with persistent mastitis at dry-off [19]. Strains Sa3151 ( spa t13401) and Sa3181 ( spa t267) were obtained from the Canadian Bovine Mastitis and Milk Quality Research Network (CBMMQRN) Mastitis Pathogen Culture Collection, and were isolated from cases of subclinical IMIs.…”

Section: Methodsmentioning

confidence: 99%

“…aureus genes that were highly expressed during bovine IMIs [19]. One gene ( guaA ) was shown to be a good target for a new drug therapy [20], and other genes were further investigated as vaccine candidates.…”

Section: Introductionmentioning

confidence: 99%

“…The importance of gene vraG in S . aureus virulence was also demonstrated by the significant attenuation of growth observed for the gene inactivation mutant during bovine IMI [19]. …”

Section: Introductionmentioning

confidence: 99%

“…Inactivation of gene vraG , should prevent cationic peptide resistance [30–32] and reduce virulence [19], while inactivation of gene hemB creates a stable SCV and prevents reversion to the invasive phenotype, a phenomenon normally seen during S . aureus infections [33].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of a vraG Mutant in a Genetically Stable Staphylococcus aureus Small-Colony Variant and Preliminary Assessment for Use as a Live-Attenuated Vaccine against Intrammamary Infections

et al. 2016

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Staphylococcus aureus is a leading cause of bovine intramammary infections (IMIs) that can evolve into difficult-to-treat chronic mastitis. To date, no vaccine formulation has shown high protective efficacy against S. aureus IMI, partly because this bacterium can efficiently evade the immune system. For instance, S. aureus small colony variants (SCVs) have intracellular abilities and can persist without producing invasive infections. As a first step towards the development of a live vaccine, this study describes the elaboration of a novel attenuated mutant of S. aureus taking advantage of the SCV phenotype. A genetically stable SCV was created through the deletion of the hemB gene, impairing its ability to adapt and revert to the invasive phenotype. Further attenuation was obtained through inactivation of gene vraG (SACOL0720) which we previously showed to be important for full virulence during bovine IMIs. After infection of bovine mammary epithelial cells (MAC-T), the double mutant (ΔvraGΔhemB) was less internalized and caused less cell destruction than that seen with ΔhemB and ΔvraG, respectively. In a murine IMI model, the ΔvraGΔhemB mutant was strongly attenuated, with a reduction of viable counts of up to 5-log10 CFU/g of mammary gland when compared to the parental strain. A complete clearance of ΔvraGΔhemB from glands was observed whereas mortality rapidly (48h) occurred with the wild-type strain. Immunization of mice using subcutaneous injections of live ΔvraGΔhemB raised a strong immune response as judged by the high total IgG titers measured against bacterial cell extracts and by the high IgG2a/IgG1 ratio observed against the IsdH protein. Also, ΔvraGΔhemB had sufficient common features with bovine mastitis strains so that the antibody response also strongly recognized strains from a variety of mastitis associated spa types. This double mutant could serve as a live-attenuated component in vaccines to improve cell-mediated immune responses against S. aureus IMIs.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The importance of gene vraG in S . aureus virulence was also demonstrated by the significant attenuation of growth observed for the gene inactivation mutant during bovine IMI [19]. …”

Section: Introductionmentioning

confidence: 99%