Abstract
Antimicrobial peptides (AMPs) have been proposed as new class of antimicrobial drugs, following the increasing prevalence of bacteria resistant to antibiotics. Synthetic AMPs are functional analogues of highly evolutionarily conserved immune effectors in animals and plants, produced in response to microbial infection. Therefore, the proposed therapeutic use of AMPs bears the risk of ‘arming the enemy’: bacteria that evolve resistance to AMPs may be cross-resistant to immune effectors (AMPs) in their hosts. We used a panel of populations of Staphylococcus aureus that were experimentally selected for resistance to a suite of individual AMPs and antibiotics to investigate the ‘arming the enemy’ hypothesis. We tested whether the selected strains showed higher survival in an insect model (Tenebrio molitor) and cross-resistance against other antimicrobials in vitro. A population selected for resistance to the antimicrobial peptide iseganan showed increased in vivo survival, but was not more virulent. We suggest that increased survival of AMP-resistant bacteria almost certainly poses problems to immune-compromised hosts.
Highlights
Antimicrobial peptides (AMPs) are major components of immune defences in multicellular organisms (Tzou et al 2002; Koprivnjak and Peschel 2011)
Of the AMP-selected lines, iseganan-selected bacteria showed higher survival in the host than the ancestor, and pexiganan-selected bacteria showed a trend towards higher survival
Streptomycin-selected bacteria showed increased survival compared with the ancestral strain as well as the unselected control strain
Summary
Antimicrobial peptides (AMPs) are major components of immune defences in multicellular organisms (Tzou et al 2002; Koprivnjak and Peschel 2011). Bacterial resistance to AMPs is rarely observed in environmental or clinical isolates, leading some to suggest that these molecules are ‘resistance proof’ (Zasloff 2002). Based on these observations and the decline in effectiveness of antibiotics, AMPs have been proposed as the basis of synthetic drugs that could be used to fight human infection (Zasloff 2002; Reddy et al 2004; Giuliani et al 2007). Recent work has shown that pexiganan-resistant S. aureus can be cross-resistant to human neutrophil defensin-1, a human AMP (Habets and Brockhurst 2012)
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