2. Academic Validation
  3. Environmental fatty acids enable emergence of infectious Staphylococcus aureus resistant to FASII-targeted antimicrobials

Environmental fatty acids enable emergence of infectious Staphylococcus aureus resistant to FASII-targeted antimicrobials

  • Nat Commun. 2016 Oct 5;7:12944. doi: 10.1038/ncomms12944.
Claire Morvan 1,  David Halpern 1,  Gérald Kénanian 1,  Constantin Hays 2 3 4 5,  Jamila Anba-Mondoloni 1,  Sophie Brinster 2 3 4,  Sean Kennedy 6,  Patrick Trieu-Cuot 7 8,  Claire Poyart 2 3 4 5,  Gilles Lamberet 1,  Karine Gloux 1,  Alexandra Gruss 1
Affiliations

Affiliations

  • 1 Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas 78350, France.
  • 2 'Barriers and Pathogens' Team, INSERM U 1016, Institut Cochin, Paris F-75014, France.
  • 3 CNRS UMR 8104, Paris F-75014, France.
  • 4 Université Paris Descartes, Sorbonne Paris Cité, Paris F-75014, France.
  • 5 Hôpitaux Universitaires Paris Centre Cochin-Hôtel Dieu-Broca, Assistance Publique Hôpitaux de Paris, Paris F-75014, France.
  • 6 Metagenopolis-Micalis UMR 1319, Jouy en Josas 78352, France.
  • 7 Biology of Gram-positive Pathogens Unit. Institut Pasteur 25-28 rue du docteur Roux, Paris 75015, France.
  • 8 CNRS ERL3526, Paris 75015, France.
PMID: 27703138 DOI: 10.1038/ncomms12944
Abstract

The Bacterial pathway for fatty acid biosynthesis, FASII, is a target for development of new anti-staphylococcal drugs. This strategy is based on previous reports indicating that self-synthesized fatty acids appear to be indispensable for Staphylococcus aureus growth and virulence, although other bacteria can use exogenous fatty acids to compensate FASII inhibition. Here we report that staphylococci can become resistant to the FASII-targeted inhibitor triclosan via high frequency mutations in fabD, one of the FASII genes. The fabD mutants can be conditional for FASII and not require exogenous fatty acids for normal growth, and can use diverse fatty acid combinations (including host fatty acids) when FASII is blocked. These mutants show cross-resistance to inhibitors of other FASII Enzymes and are infectious in mice. Clinical isolates bearing fabD polymorphisms also bypass FASII inhibition. We propose that fatty acid-rich environments within the host, in the presence of FASII inhibitors, might favour the emergence of staphylococcal strains displaying resistance to multiple FASII inhibitors.

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