In vitro resistance to thrombin-induced platelet microbicidal protein is associated with enhanced progression and hematogenous dissemination in experimental Staphylococcus aureus infective endocarditis

Abstract

We examined the influence of thrombin-induced platelet microbicidal protein 1 (tPMP-1) on the progression and hematogenous dissemination of experimental endocarditis caused by isogenic Staphylococcus aureus strains differing in tPMP susceptibility (tPMPs) or resistance (tPMPr) in vitro. Following simultaneous challenge of animals with both strains, significantly higher tPMPr bacterial densities were present in vegetations (P < 0.0001), kidneys (P < 0. 0001), and spleens (P < 0.0001) compared with those for the tPMPs strain. These data indicate that tPMP-1 limits the intravegetation proliferation and hematogenous dissemination of a tPMPs strain in experimental endocarditis, while the tPMPr phenotype confers a selective advantage associated with the enhanced progression of this infection.

FIG. 1

Comparison of S. aureus ISP479C and ISP479R growth kinetics in vitro. Log-phase organisms were dually inoculated (10³ CFU of each strain) into 10 ml of BHI broth, and the cultures were incubated on a rotary shaker (for aeration) at 37°C. At selected time points, aliquots were quantitatively cultured on BHI agar with or without erythromycin (10 μg/ml; as described in Materials and Methods). Data points represent the mean values from two independent experiments performed in duplicate. In no case was the deviation from the mean greater than 0.2 log CFU/ml; error bars were intentionally excluded to improve clarity. These results mirrored those of identical dual-culture experiments performed with nutrient or Trypticase soy broth (see Materials and Methods). These results were not significantly different from those for either organism cultured alone (data not shown).