Abstract
Virulence factors and biofilms constitute attractive targets for the prevention of infections caused by multidrug-resistant bacteria. Among alkyl gallates, propyl gallate (PG) and octyl gallate (OG) are used as food preservatives. Here we found that alkyl gallates differentially affect virulence, biofilm formation, and quorum sensing (QS) in Pseudomonas aeruginosa. Ethyl gallate (EG), PG, and butyl gallate (BG) inhibited biofilm formation and virulence factors including elastase, pyocyanin, and rhamnolipid, in P. aeruginosa without affecting cell viability by antagonizing the QS receptors LasR and RhlR. PG exhibited the most potent activity. Interestingly, hexyl gallate (HG) inhibited the production of rhamnolipid and pyocyanin but did not affect elastase production or biofilm formation. Notably, OG inhibited the production of rhamnolipid and pyocyanin but stimulated elastase production and biofilm formation. Analysis of QS signaling molecule production and QS gene expression suggested that HG inhibited RhlR, while OG activated LasR but inhibited PqsR. This mechanism was confirmed using QS mutants. Additionally, PG prevented the virulence of P. aeruginosa in Caenorhabditis elegans and a mouse model. This is the first report of the differential effects of alkyl gallates on QS systems and PG has great potential as an inhibitor of the virulence and biofilm formation of P. aeruginosa.
Highlights
Quorum sensing (QS) is a bacterial communication system that uses small diffusible signal molecules known as autoinducers
The effects of alkyl gallates on the production of elastase, pyocyanin, and rhamnolipid by P. aeruginosa PAO1 cells were evaluated
hexyl gallate (HG) and octyl gallate (OG) exhibited antibacterial activity within the range required for inhibition of elastase production (Fig. 1a)
Summary
Quorum sensing (QS) is a bacterial communication system that uses small diffusible signal molecules known as autoinducers. Traditional strategies for the prevention and treatment of bacterial infections are based on the use of antibacterial compounds that kill bacteria or inhibit the growth of bacteria. These strategies have resulted in substantial stress on target bacteria, causing the rapid growth of resistant populations[4]. P. aeruginosa has been shown to form biofilms in the CF lung, which increase bacterial resistance to antibiotics[7], and produce several virulence factors including elastase, rhamnolipid, and pyocyanin. The inhibition of virulence factor production and biofilm formation may be highly attractive for the prevention and treatment of P. aeruginosa infections[8]. Phenolic compounds, including methyl gallate (MG), have been reported to exhibit antibiofilm activity against Streptococcus mutans and anti-QS activity against P. aeruginosa, but the antivirulence activity of alkyl gallates, especially PG and OG, has not been studied to date[22,23,24]
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