Article
Susceptibility of clinical Staphylococcus aureus isolates against innate defense antimicrobial peptides
Empfindlichkeit klinischer Staphylococcus aureus-Isolate gegenüber antimikrobiellen Peptiden der Innate defense
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Published: | June 2, 2010 |
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Objectives: Antimicrobial peptides (AMPs) are ascribed to play an important role in innate immunity as first line of defense against invading pathogens. Although diverse AMP resistance mechanisms and their impact on pathogenesis in animal models have been characterised, data on AMP susceptibility of well-characterised clinical isolates are scarce. Thus, we sought to determine AMP resistance levels in clinical isolates of S. aureus with different invasive potential.
Methods: Fifty-eight S. aureus isolates of patients with S. aureus bacteremia (SAB) that were evaluated within the INvasive STaph. aureus INfectionS CohorT (INSTINCT), 15 isolates of patients suffering from recurrent skin infections (furunculosis, abscesses) and 23 colonising isolates (nares or skin) of healthy carriers were investigated. AMPs tested in our study were human cathelicidin LL-37/hCAP-18, human β-defensin hBD-3 and bovine indolicidin. AMP susceptibility was investigated by means of a modified NCCLS microbroth dilution assay. Minimum concentration for inhibition of growth in broth (MCB) of each isolate was determined in triplicate, and median values were compared by Wilcoxon rank-sum test.
Results: HBD-3 and indolicidin (MCB range, 4–16 µg/ml, respectively) revealed more potent antistaphylococcal activity than cathelicidin LL-37 (range, 12–128 µg/ml). Compared to colonising isolates, S. aureus strains isolated from recurrent abscesses/furuncles were found to have slightly higher MCBs of hBD-3 (p=0.052), LL-37 (p=0.15) and indolicidin (p=0.18). SAB isolates revealed significantly higher MCBs of hBD-3 (p<0.01) and indolicidin (p=0.04) when compared to non-invasive colonising isolates. Within the SAB group, MCB values of isolates from uncomplicated catheter-related bacteremia did not differ from those of isolates from complicated SAB with unknown portal of entry.
Conclusion: Our investigation reveals that S. aureus isolates causing recurrent skin infections and isolates involved in invasive infections (i.e. bacteremia) are moderately more resistant against selected epithelia- and/or leukocyte-derived AMPs than colonising isolates. Thus, AMP resistance may represent a distinct virulence property of invading pathogens and, as shown here, may contribute to clinical manifestations and severity of disease.