Influence of Platelets and Platelet Microbicidal Protein Susceptibility on the Fate of Staphylococcus aureus in an In Vitro Model of Infective Endocarditis

Abstract

Several lines of evidence indicate that platelets protect against endovascular infections such as infective endocarditis (IE). It is highly likely that a principal mechanism of this platelet host defense role is the release of platelet microbicidal proteins (PMPs) in response to agonists generated at sites of endovascular infection. We studied the ability of platelets to limit the colonization and proliferation of Staphylococcus aureus in an in vitro model of IE. Three isogenic S. aureus strains, differing in their in vitro susceptibility to thrombin-induced platelet microbicidal protein-1 (tPMP), were used: ISP479C (parental strain; highly susceptible to tPMP . The latter differences were observed despite there being no detectable differences among the three S. aureus strains in initial colonization of simulated vegetations. Collectively, these data indicate that platelets limit intravegetation proliferation of tPMP s but not tPMP r S. aureus. These findings underscore the likelihood that platelets play an important antimicrobial host defense role in preventing and/or limiting endovascular infections due to tPMP s pathogens.

Inflammatory Response in Infective Endocarditis

“…These peptides limit the progression of the disease. Staphylococcus aureus strains resistant to tPMP may grow faster in the presence oftPMP than susceptible strains, and the vegetation size rate and progression rate was higher in rabbits infected by tPMP resistant strains (14)(15)(16). tPMP susceptibility of the infective organism may affect the entire course of the disease regarding both local and systemic lesions.…”

Platelet Antistaphylococcal Responses Occur through P2X 1 and P2Y 12 Receptor-Induced Activation and Kinocidin Release

“…ISP479R exhibits reduced killing by low levels of tPMP-1 in vitro (e.g., Ն90% survival of a 10 3 CFU/ml inoculum following 2 h of exposure to 2 g of tPMP-1 at 37°C), compared with that of tPMP-1-susceptible ISP479C (Յ25% survival under identical test conditions). These strains have been described in detail previously (24,26,36).…”

In Vitro Susceptibility to Thrombin-Induced Platelet Microbicidal Protein Is Associated With Reduced Disease Progression and Complication Rates in Experimental Staphylococcus aureus Endocarditis

“…However, given our current and prior in vitro and in vivo data, 10,[12][13][14][15] it appears reasonable to hypothesize that the local secretion of tPMPs from activated platelets at sites of vegetation development may limit proliferation of tPMP-susceptible strains. This effect would likely mitigate hematogenous embolic seeding of target organs (eg, kidneys) and reduce the extent of bacteremia, key factors in ongoing microbial seeding of vegetations.…”

“…8 A compelling body of recent evidence has demonstrated that the host defense function of these peptides is particularly relevant to endovascular infections caused by S aureus. 6,[12][13][14][15]27 For example, among clinical bloodstream S aureus isolates, tPMP-susceptible strains were infrequently associated with human IE compared with tPMP-resistant strains. 28 In addition, bacteremic S aureus strains from patients with IE, resulting from an infected intravascular catheter, tended to be significantly more tPMP-resistant than strains arising from a noncatheter source.…”

“…6,7 A growing body of evidence strongly suggests that tPMPs serve an integral role in host defense by limiting the progression of endovascular infections. [11][12][13][14][15] However, the overall relationship between microbial tPMP-susceptibility phenotypes and complications in IE has not yet been addressed. In the present study, we evaluated whether microbial differences in tPMP-susceptibility phenotypes in vitro would affect key parameters related to IE severity and prognosis, including the frequency and extent of valvular and perivalvular complications.…”