title: The impact of fatty acids on the antibacterial properties of N-thiolated β-lactams.
abstract: Bacterial fatty acid synthesis (FAS) is a potentially important, albeit controversial, target for antimicrobial therapy. Recent studies have suggested that the addition of exogenous fatty acids (FAs) to growth media can circumvent the effects of FAS-targeting compounds on bacterial growth. Consequently, such agents may have limited in vivo applicability for the treatment of human disease, as free FAs are abundant within the body. Our group has previously developed N-thiolated β-lactams and found they function by interfering with FAS in select pathogenic bacteria, including MRSA. To determine if the FAS targeting activity of N-thiolated β-lactams can be abrogated by exogenous fatty acids, we performed MIC determinations for MRSA strains cultured with the fatty acids oleic acid and Tween 80. We find that, whilst the activity of the known FAS inhibitor triclosan is severely compromised by the addition of both oleic acid and Tween 80, exogenous FAs do not mitigate the antibacterial activity of N-thiolated β-lactams towards MRSA. Consequently, we propose that N-thiolated β-lactams are unique amongst FAS-inhibiting antimicrobials, as their effects are unimpeded by exogenous FAs.
authors.affiliation: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Prosen
authors.forename: Ronan K
authors.initials: RK
authors.lastname: Carroll
authors.forename: Whittney N
authors.initials: WN
authors.lastname: Burda
authors.forename: Christina N
authors.initials: CN
authors.lastname: Krute
authors.forename: Biplob
authors.initials: B
authors.lastname: Bhattacharya
authors.forename: My Lien
authors.initials: ML
authors.lastname: Dao
authors.forename: Edward
authors.initials: E
authors.lastname: Turos
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Shaw
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D005227:Fatty Acids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016106:Methicillin Resistance / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D047090:beta-Lactams / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D047090:beta-Lactams