Genetic Diversity of Staphylocoagulase Genes (coa): Insight into the Evolution of Variable Chromosomal Virulence Factors in Staphylococcus aureus

Abstract

BackgroundThe production of staphylocoagulase (SC) causing the plasma coagulation is one of the important characteristics of Staphylococcus aureus. Although SCs have been classified into 10 serotypes based on the differences in the antigenicity, genetic bases for their diversities and relatedness to chromosome types are poorly understood.Methodology/Principal FindingsWe compared the nucleotide sequences of 105 SC genes (coa), 59 of which were determined in this study. D1 regions, which contain prothrombin-activating and -binding domains and are presumed to be the binding site of each type-specific antiserum, were classified into twelve clusters having more than 90% nucleotide identities, resulting to create two novel SC types, XI and XII, in addition to extant 10 types. Nine of the twelve SC types were further subdivided into subtypes based on the differences of the D2 or the central regions. The phylogenetical relations of the D1 regions did not correlate exactly with either one of agr types and multilocus sequence types (STs). In addition, genetic analysis showed that recombination events have occurred in and around coa. So far tested, STs of 126 S. aureus strains correspond to the combination of SC type and agr type except for the cases of CC1 and CC8, which contained two and three different SC types, respectively.ConclusionThe data suggested that the evolution of coa was not monophyletic in the species. Chromosomal recombination had occurred at coa and agr loci, resulting in the carriage of the combinations of allotypically different important virulence determinants in staphylococcal chromosome.

Impact of rpoB Mutations on Reduced Vancomycin Susceptibility in Staphylococcus aureus

“…All of the strains were susceptible to vancomycin and rifampin, with MICs of Յ2 and Ͻ0.25 g/ml, respectively (Table 1). They belonged to the type IIA SCCmec-type II coagulase that corresponds to the most dominant Japanese hospital-associated MRSA (HA-MRSA) clone with the ST5 genotype (20,23). A total of 10 7 CFU of MRSA cells were inoculated on brain heart infusion (BHI) agar plates containing 10 g/ml rifampin, and rifampin-resistant colonies that appeared on the plates were picked after 24 h of incubation at 37°C.…”

Coagulases as Determinants of Protective Immune Responses against Staphylococcus aureus

“…In agreement with this model, the expression of coa and vwb is a universal trait of S. aureus strains (5). Of note, the coa gene of S. aureus isolates is variable (29), with a greater variation in amino acid sequence than even the tandem repeats of the protein A (spa) gene; the variation in spa is used for epidemiological typing experiments (20,43). S. aureus mutants that are unable to express coa have not yet been isolated from humans with manifest staphylococcal disease.…”

“…The latter is accomplished via multilocus sequence typing (MLST), which examines sequences from seven different genes (arc, aro, glp, gmk, pta, tpi, and yqi) (11). With the exception of CC1 and CC8 strains, which frequently harbor different coa types, most of the isolates categorized as a single CC type by MLST also harbor a single coa sequence type (43). The variation of coa sequences is likely generated via horizontal gene transfer (for example, phage transduction or DNA transformation), because coa genes of the same sequence type are found scattered across the MLST tree (43).…”

“…With the exception of CC1 and CC8 strains, which frequently harbor different coa types, most of the isolates categorized as a single CC type by MLST also harbor a single coa sequence type (43). The variation of coa sequences is likely generated via horizontal gene transfer (for example, phage transduction or DNA transformation), because coa genes of the same sequence type are found scattered across the MLST tree (43). Together with the observation that pooled human immunoglobulin neutralizes most, but not all, coagulase types (40), these analyses suggest that coa gene diversification may enable S. aureus to circumvent the humoral immune responses of hosts with prior exposure to the pathogen (43).…”

“…The variation of coa sequences is likely generated via horizontal gene transfer (for example, phage transduction or DNA transformation), because coa genes of the same sequence type are found scattered across the MLST tree (43). Together with the observation that pooled human immunoglobulin neutralizes most, but not all, coagulase types (40), these analyses suggest that coa gene diversification may enable S. aureus to circumvent the humoral immune responses of hosts with prior exposure to the pathogen (43). If so, Coa may represent a protective antigen of S. aureus and should be analyzed for its possible use as a vaccine antigen.…”