Related Experiment Videos
In vitro resistance to thrombin-induced platelet microbicidal protein among clinical bacteremic isolates of
A S Bayer1, D Cheng, M R Yeaman
1The St. John's Cardiovascular Research Center and the Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, California 90509, USA. Bayer@HUMC.EDU
Abstract:
Platelet microbicidal proteins (PMPs), small cationic peptides released at sites of endovascular damage, kill common bloodstream pathogens in vitro. Our group previously showed that in vitro resistance of clinical staphylococcal and viridans group streptococcal bacteremic strains to PMPs correlated with the diagnosis of infective endocarditis (IE) (Wu et al., Antimicrob. Agents Chemother. 38:729-732, 1994). However, that study was limited by (i) the small number of Staphylococcus aureus isolates from IE patients, (ii) the retrospective nature of the case definitions, and (iii) the diverse geographic sources of strains. The present study evaluated the in vitro PMP susceptibility phenotype of a large number of staphylococcemic isolates (n = 60), collected at a single medical center and categorized by defined and validated clinical criteria. A significantly higher proportion of staphylococcemic strains from patients with IE was PMP resistant in vitro than the proportion of strains from patients with soft tissue sepsis (83% and 33%, respectively; P < 0.01). Moreover, the levels of PMP resistance (mean percent survival of strains after 2-h exposure to PMP in vitro) were significantly higher for isolates from patients with IE and with vascular catheter sepsis than for strains from patients with abscess sepsis (P < 0.005 and P < 0.01, respectively). These data further support the concept that bloodstream pathogens that exhibit innate or acquired PMP resistance have a survival advantage with respect to either the induction or progression of endovascular infections.
Insights
Platelet microbicidal proteins (PMPs) resist common bloodstream pathogens. PMP resistance in Staphylococcus strains is linked to infective endocarditis, suggesting a survival advantage for these pathogens in endovascular infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Biochemistry
Background:
- Platelet microbicidal proteins (PMPs) are cationic peptides that combat bloodstream pathogens.
- Previous research indicated a correlation between PMP resistance in staphylococcal and streptococcal strains and infective endocarditis (IE).
- Limitations in prior studies included small sample sizes, retrospective case definitions, and diverse strain origins.
Purpose of the Study:
- To investigate the in vitro PMP susceptibility of a larger cohort of staphylococcal isolates.
- To correlate PMP resistance phenotypes with specific clinical diagnoses, including IE, soft tissue sepsis, vascular catheter sepsis, and abscess sepsis.
- To further elucidate the role of PMP resistance in the pathogenesis of endovascular infections.
Main Methods:
- Evaluation of the in vitro PMP susceptibility phenotype of 60 staphylococcal isolates from a single medical center.
- Clinical data for isolates were categorized using defined and validated criteria.
- Statistical analysis was performed to compare PMP resistance proportions and levels across different infection types.
Main Results:
- A significantly higher proportion of staphylococcal strains from IE patients (83%) exhibited in vitro PMP resistance compared to those from soft tissue sepsis patients (33%) (P < 0.01).
- Isolates from IE and vascular catheter sepsis showed significantly higher levels of PMP resistance than those from abscess sepsis (P < 0.005 and P < 0.01, respectively).
- The mean percent survival of strains after PMP exposure was notably higher in IE and catheter sepsis groups.
Conclusions:
- In vitro PMP resistance is significantly more prevalent in staphylococcal strains causing infective endocarditis compared to other sepsis types.
- Elevated levels of PMP resistance are associated with IE and vascular catheter-associated sepsis.
- These findings support the hypothesis that PMP resistance confers a survival advantage to bloodstream pathogens, facilitating the development or progression of endovascular infections.