Potential associations between severity of infection and the presence of virulence-associated genes in clinical strains of Staphylococcus aureus

Abstract

Background: The clinical spectrum of Staphylococcus aureus infection ranges from asymptomatic nasal carriage to osteomyelitis, infective endocarditis (IE) and death. In this study, we evaluate potential association between the presence of specific genes in a collection of prospectively characterized S. aureus clinical isolates and clinical outcome.

Methodology/principal findings: Two hundred thirty-nine S. aureus isolates (121 methicillin-resistant S. aureus [MRSA] and 118 methicillin-susceptible S. aureus [MSSA]) were screened by array comparative genomic hybridization (aCGH) to identify genes implicated in complicated infections. After adjustment for multiple tests, 226 genes were significantly associated with severity of infection. Of these 226 genes, 185 were not in the SCCmec element. Within the 185 non-SCCmec genes, 171 were less common and 14 more common in the complicated infection group. Among the 41 genes in the SCCmec element, 37 were more common and 4 were less common in the complicated group. A total of 51 of the 2014 sequences evaluated, 14 non-SCCmec and 37 SCCmec, were identified as genes of interest.

Conclusions/significance: Of the 171 genes less common in complicated infections, 152 are of unknown function and may contribute to attenuation of virulence. The 14 non-SCCmec genes more common in complicated infections include bacteriophage-encoded genes such as regulatory factors and autolysins with potential roles in tissue adhesion or biofilm formation.

Figure 1. Disposition of 4544 aCGH probes.

This figure illustrates how we arrived at our candidate genes of interest. Of the 2014 sequences and 239 isolates, a total of 226 sequences were statistically significant after multiple comparisons adjustment. Of these 226 sequences, 185 were not and 41 were in the SCCmec element. Most of the 185 non-SCCmec genes-171-were significantly less common in the complicated infection group. The remaining 14 genes were significantly more common in isolates from the complicated infection group. Among the 41 SCCmec element genes, 37 were significantly more common in the complicated group and 4 were significantly less common in the complicated group. Therefore, a total of 51 of the 2014 sequences, 14 non-mec associated and 37 mec associated, were identified as genes of interest.

Figure 2. Distribution of 14 genes associated with complicated infections across clonal complexes.

Proportion of isolates that have the 14 genes in each clonal complex shown on a color gradient with 1 being bright red and 0 being bright blue. All 14 genes are more abundant in CC5 and 30, the clonal complexes previously shown to exhibit a significant trend toward increasing levels of hematogenous complications.