Altered Virulence of a Pleiotropic <i>Staphylococcus aureus</i> Mutant with a Low Producibility of Coagulase and Other Factors in Mice

Seki, Kazuhiko; Ogasawara, Masahito; Sakurada, Junji; Murai, Miyo; Masuda, Shōgo

doi:10.1111/j.1348-0421.1989.tb03156.x

Cited by 15 publications

(14 citation statements)

References 18 publications

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“…Coagulase activity from each strain was determined on PAF200RP plate (5 was performed by a convenient method (6) devised by our group using a commercially available set of type-specific antisera (Denka Seiken). Statistical analyses were made using the x2 test.…”

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confidence: 99%

Occurrence of Coagulase Serotype among Staphylococcus aureus Strains Isolated from Healthy Individuals —Special Reference to Correlation with Size of Protein‐A Gene—

Seki

Sakurada

Seong

et al. 1998

Microbiology and Immunology

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One-hundred-and-nineteen strains of Staphylococcus aureus isolated from healthy individuals for 3 years between 1991 and 1993 were subjected to an investigation on the producibility of proteins including protein A, coagulase, enterotoxins and toxic-shock syndrome toxin-1. Especially, protein A was the center of our interest. Among these strains, 69, 43, 3 and 1 strains were found to have the protein-A gene containing 5, 4, 3 and 2 IgG-binding domains, respectively. On the other hand, only one strain was devoid of the protein-A gene. There were some differences in the profile of the coagulase serotype between the group with 4 IgG-binding domains and that with 5 IgG-binding domains. Differences in the profile of toxin production were also observed between the two groups.

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confidence: 99%

Occurrence of Coagulase Serotype among Staphylococcus aureus Strains Isolated from Healthy Individuals —Special Reference to Correlation with Size of Protein‐A Gene—

Seki

Sakurada

Seong

et al. 1998

Microbiology and Immunology

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“…Although staphylocoagulase is classically considered to be a virulence factor, the available evidence from animal infection models is conflicting. Some studies showed decreased virulence of coagulase-negative mutants (1,7,8,12,20), but these mutant strains arose from nonspecific increased mutagenesis and probably had inherently reduced virulence compared to the nonmutant parent strain. Coagulase-negative mutants obtained by site-specific mutagenesis showed reduced virulence in a murine hematogenous pulmonary infection model (18), and inhibition of coagulase activity using inhibitory RNA reduced bacterial loads in an animal S. aureus bacteremia model (24), showing the potential of coagulase inhibition strategies in these settings.…”

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Dabigatran Inhibits Staphylococcus aureus Coagulase Activity

et al. 2010

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The ability of Staphylococcus aureus to clot plasma through conformational activation of prothrombin by staphylocoagulase is used to distinguish S. aureus from coagulase-negative staphylococci. We show that while the direct thrombin inhibitor dabigatran inhibits staphylocoagulase activity, the clinical use of dabigatran etexilate is not expected to interfere with direct tube coagulase testing.Since the early notion, developed more than a century ago, that the ability to clot plasma correlates with the pathogenic potential of staphylococci (3,14), this phenomenon has been used to distinguish Staphylococcus aureus from less virulent, coagulase-negative staphylococci. Although the use of new molecular methods for rapid identification of S. aureus from blood culture bottles is expanding (15, 17), detection of coagulase activity by direct tube coagulase (DTC) testing remains a costeffective, easy to perform, and reliable method for early detection of S. aureus in blood culture broth with a Gram stain result suggestive of staphylococci (10,13,16,23). Since false-negative results increase the therapeutic delay, the carryover of contaminants from either the culture broth or the patient's plasma that interfere with the tube test clotting reaction has to be avoided (23).Clotting occurs when fibrinogen is converted into fibrin by thrombin. Under physiological conditions, the proteolytic activation of the inactive precursor prothrombin into thrombin is the final step in the tightly regulated coagulation cascade. Staphylocoagulase secreted by S. aureus directly binds to prothrombin to form the staphylothrombin complex and thus bypasses the coagulation cascade and its physiological regulation (6). As a consequence of this unique nonproteolytic direct thrombin activation, treatment with heparins, vitamin K antagonists, or the thrombin inhibitor hirudin does not interfere with staphylothrombin function (9) and is of no concern for DTC testing.In view of the recent availability and increasing clinical use of the new direct thrombin inhibitor dabigatran etexilate, we studied whether dabigatran inhibits staphylocoagulase and whether clinical use of dabigatran etexilate is expected to interfere with DTC testing.To test these possibilities, we measured coagulation of citrated human plasma as the change in absorbance at 405 nm (A 405 ) after the addition of purified staphylocoagulase (3 nM) in the presence of increasing concentrations (0, 0.625, 1.25, 2.5, 5, and 10 nM) of dabigatran (Boehringer Ingelheim

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“…and i.p. LD 50 infections, and murine mastitis [112, 126–129]. However the mode of mutagenesis and mutant selection may have also led to additional mutations, for example in important virulence regulatory genes.…”

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Exploring Staphylococcus aureus pathways to disease for vaccine development

et al. 2011

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Staphylococcus aureus is a commensal of the human skin or nares and a pathogen that frequently causes skin and soft tissue infections as well as bacteremia and sepsis. Recent efforts in understanding the molecular mechanisms of pathogenesis revealed key virulence strategies of S. aureus in host tissues: bacterial scavenging of iron, induction of coagulation pathways to promote staphylococcal agglutination in the vasculature, and suppression of innate and adaptive immune responses. Advances in all three areas have been explored for opportunities in vaccine design in an effort to identify the critical protective antigens of S. aureus. Human clinical trials with specific subunit vaccines have failed, yet provide important insights for the design of future trials that must address the current epidemic of S. aureus infections with drug-resistant isolates (MRSA, methicillin-resistant S. aureus).

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Altered Virulence of a Pleiotropic Staphylococcus aureus Mutant with a Low Producibility of Coagulase and Other Factors in Mice

Cited by 15 publications

References 18 publications

Occurrence of Coagulase Serotype among Staphylococcus aureus Strains Isolated from Healthy Individuals —Special Reference to Correlation with Size of Protein‐A Gene—

Occurrence of Coagulase Serotype among Staphylococcus aureus Strains Isolated from Healthy Individuals —Special Reference to Correlation with Size of Protein‐A Gene—

Dabigatran Inhibits Staphylococcus aureus Coagulase Activity

Exploring Staphylococcus aureus pathways to disease for vaccine development

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