title: Simultaneous inhibition of rhamnolipid and polyhydroxyalkanoic acid synthesis and biofilm formation in Pseudomonas aeruginosa by 2-bromoalkanoic acids: effect of inhibitor alkyl-chain-length.
abstract: Pseudomonas aeruginosa, an opportunistic human pathogen is known to synthesize rhamnolipid and polyhydroxyalkanoic acid (PHA) of which the acyl-group precursors (e.g., (R)-3-hydroxydecanoic acid) are provided through RhlA and PhaG enzyme, respectively, which have 57% gene sequence homology. The inhibitory effect of three 2-bromo-fatty acids of 2-bromohexanoic acid (2-BrHA), 2-bromooctanoic acid (2-BrOA) and 2-bromodecanoic acid (2-BrDA) was compared to get an insight into the biochemical nature of their probable dual inhibition against the two enzymes. The 2-bromo-compounds were found to inhibit rhamnolipid and PHA synthesis simultaneously in alkyl-chain-length dependent manner at several millimolar concentrations. The separate and dual inhibition of the RhlA and PhaG pathway by the 2-bromo-compounds in the wild-type cells was verified by investigating their inhibitory effects on the rhamnolipid and PHA synthesis in P. aeruginosa ΔphaG and ΔrhlA mutants. Unexpectedly, the order of inhibition strength was found 2-BrHA (≥90% at 2 mM) > 2-BrOA > 2-BrDA, equally for all of the rhamnolipids and PHA synthesis, swarming motility and biofilm formation. We suggest that the novel strongest inhibitor 2-BrHA could be potentially exploited to control the rhamnolipid-associated group behaviors of this pathogen as well as for its utilization as a lead compound in screening for antimicrobial agents based on new antimicrobial targets.
authors.affiliation: Nano-Biomaterials Science Laboratory, Division of Applied Life Sciences, Graduate School, Gyeongsang National University, Jinju, Republic of Korea ; National Research Foundation Funded Pioneer Research Center for Alzheimer Disease Control, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Merced
authors.initials: M
authors.lastname: Gutierrez
authors.forename: Mun Hwan
authors.initials: MH
authors.lastname: Choi
authors.forename: Baoxia
authors.initials: B
authors.lastname: Tian
authors.forename: Ju
authors.initials: J
authors.lastname: Xu
authors.forename: Jong Kook
authors.initials: JK
authors.lastname: Rho
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: You-Hee
authors.initials: YH
authors.lastname: Cho
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Yoon
mesh_terms: D000123:Acetyltransferases / Q000037:antagonists & inhibitors; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development*; D002264:Carboxylic Acids / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006017:Glycolipids / Q000096:biosynthesis*; D008190:Lyases / Q000037:antagonists & inhibitors; D009068:Movement / Q000187:drug effects; D054813:Polyhydroxyalkanoates / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D002264:Carboxylic Acids; D005227:Fatty Acids; D006017:Glycolipids; D054813:Polyhydroxyalkanoates; C418382:rhamnolipid; D000123:Acetyltransferases; D008190:Lyases
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