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.
Highlights
Pseudomonas aeruginosa is a typical opportunistic human pathogen which colonizes the lungs of cystic fibrosis patients and causes serious infections in immuno-compromised hosts [1]
In previous inhibitor screening studies, we reported that 2-bromooctanoic acid (2-BrOA) inhibits MCL-polyhydroxyalkanoic acid (PHA) synthesis by Pseudomonas fluorescens BM07 from fructose, without any influence on cell growth [32,33]
Similar decreases in production depending on the type of inhibitor were observed for P. aeruginosa PAO1 grown on 70 mM fructose medium with 2 mM 2-bromo-compounds: from 13 wt% and 1.82 g/l to 1.4 wt% and 0.19 g/l for 2-BrHA, 3.8 wt% and 0.55 g/l for 2-BrOA and 9.5 wt% and 1.80 g/l for 2-bromodecanoic acid (2-BrDA), respectively (Table 1, Figure 2E and F)
Summary
Pseudomonas aeruginosa is a typical opportunistic human pathogen which colonizes the lungs of cystic fibrosis patients and causes serious infections in immuno-compromised hosts [1]. The effect of the three 2-bromo-compounds (2-BrHA, 2-BrOA and 2-BrDA) on the PHA and rhamnolipid synthesis in P. aeruginosa strains PA14 and PAO1 was investigated (Table 1).
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