In the current investigation we used a collection of clinically well-characterized S. aureus isolates from patients with same type of infection (cSSSI) from different regions of the globe to evaluate potential associations between bacterial genotype and clinical outcome. Our investigation yielded several key observations.
First, our results demonstrated the impact of geography on the genetic composition of S. aureus
, even among isolates associated with the same form of infection. In the current study, strains of MSSA causing skin and soft tissue infections in South Africa were significantly more likely to contain a variety of toxins or leukocidins, including pvl
, than MSSA isolates causing similar infections in the United States. Interestingly, these genes are known to be contained on mobile genetic elements, such as pathogenicity islands and bacteriophages (23
). Thus, this observation could be due to regional dissemination of S. aureus
clones containing these mobile genetic elements. In addition, the PFGE patterns of the South African and U.S. isolates were largely distinct. While our report is the first to compare detailed genotypic characteristics of S. aureus
isolates causing soft tissue infections in different regions of the globe, our findings are consistent with prior observations (3
Over 90% of the S. aureus
isolates in this investigation contained the pvl
gene. Although numerous studies have described the high rates of the pvl
gene among strains of MRSA causing skin and soft tissue infections (5
), its prevalence in the current study was higher than previously reported. There are two potential explanations for this observation. First, the investigation focused exclusively on S. aureus
isolated from skin and soft tissue infections, a clinical condition in which pvl
has been strongly associated. By contrast, many previous investigations included S. aureus
from other sites of infection in which pvl
is less frequently encountered. Second, the investigation was contemporary. As a result, the microbiology of the current investigation more accurately reflected the emergence of the USA 300 clone as the predominant cause of soft tissue infections (21
). Interestingly, the role of the pvl
product, a bi-component of leukocidin, in the pathogenesis of these infections is still a subject of debate. For example, one group of investigators concluded that pvl
was not a major virulence factor in a murine model of S. aureus
), while another group concluded that pvl
plays a critical role in the pathogenesis of S. aureus
necrotizing pneumonia (15
). In the current study, a high prevalence of pvl
was seen in both MSSA and MRSA isolates, providing further epidemiological evidence linking the presence of this gene and the occurrence of skin and soft tissue infections.
Interestingly, in the current study the presence of pvl
was significantly associated with better cure rates than infections caused by S. aureus
not containing the pvl
gene. This observation may be due in part to the high frequency of abscesses among infections caused by the pvl
-constituitive isolates (7
), as these lesions may often be treated with surgical drainage alone (16
). Patients infected with pvl
-constitutive strains of community-associated MRSA (CA-MRSA) have been shown to experience similar hospitalization rates (6
) and outcomes (18
) as patients infected with strains of MRSA not containing this gene. Finally, skin and soft tissue infections produced by CA-MRSA and CA-MSSA are not clinically distinguishable (20
). Taken together, these observations suggest that the presence of pvl
, per se, does not confer a worse clinical course in skin and soft tissue infections caused by S. aureus
in general and MRSA in particular.
Our results are consistent with a growing number of reports documenting the emerging importance of the USA 300 clone as a predominant cause of community-acquired skin and soft tissue infections in the United States (7
). All of the MRSA isolates in this study were from the United States, and most (>80%) were strain USA 300.
This investigation was designed to evaluate potential associations between the presence of putative virulence genes in S. aureus
and the outcome of skin and soft tissue infections caused by this bacteria. Our findings are consistent with prior studies. For example, Peacock and colleagues found that seven genes (fnbA
, and ica
) were significantly more common in S. aureus
isolates associated with invasive infection than in nasal carriage isolates. (26
). However, it is possible that our results may simply reflect the clonal nature of strains associated with these infections, or the genes identified in our analyses may be in linkage disequilibrium with other genes not tested in this analysis that influence the pathogenesis of these infections. Future studies should therefore focus on validating these findings using other collections of S. aureus
isolates and on evaluating the biological relevance of these associations in vivo.
This study was limited by its relatively small sample size. These isolates were collected from a clinical trial and may not necessarily be representative of the epidemiology of infections in the study area. Additionally, at least in part due to the small sample size, there were no MRSA isolates within the South African subset of our collection, while more than three-quarters of the U.S. isolates were MRSA. For this reason, it was necessary to limit the evaluation of geographical differences in virulence factors to the MSSA subset in order to minimize the confounded effects of geography and MRSA/MSSA status in our sample. Other investigations currently under way using larger international collections of S. aureus
isolates from soft tissue infections (4
) and endocarditis (10
) may be able to more fully characterize the geographical distribution of virulence factors and potentially validate the observations made in the current study. The current investigation evaluated only the presence or absence of particular genes based on PCR. Thus, it was not designed to evaluate expression of these genes or the presence of single nucleotide polymorphisms, which can influence the function of the gene products (33
). Finally, this evaluation focused by design only upon infections in which the causative organism was available for culture. As a result, these observations cannot be generalized to soft tissue infections if the pathogen cannot be cultured.
Despite these limitations, however, the results of the current investigation offer several important observations. Although the pvl gene was found in the majority of MSSA and MRSA strains causing soft tissue infection in this study, its presence was associated with a better clinical outcome. The relative distribution of virulence genes differs significantly among S. aureus strains from different parts of the world—even when these bacteria are associated with same type of infection. The genetic variation in these clinical S. aureus isolates emphasizes the diversity of this emerging cause of human infections.