title: Increased survival of experimentally evolved antimicrobial peptide-resistant Staphylococcus aureus in an animal host.
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.
authors.affiliation: Animal & Plant Sciences, University of Sheffield, Western Bank Sheffield, UK ; Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London London, UK.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Dobson
authors.affiliation: Animal & Plant Sciences, University of Sheffield, Western Bank Sheffield, UK ; School of Life Sciences, Centre for Biomolecular Science, University of Nottingham Nottingham, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Purves
authors.affiliation: Animal & Plant Sciences, University of Sheffield, Western Bank Sheffield, UK ; Institute of Biology, Free University Berlin Berlin, Germany ; Berlin-Brandenburg Institute of Advanced Biodiversity Research (BBIB) Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Rolff
keywords: experimental evolution; immunity; pathogenecity; resistance evolution.