Combined effect of linolenic acid and tobramycin on Pseudomonas aeruginosa biofilm formation and quorum sensing

Abstract

Pseudomonas aeruginosa is a ubiquitous Gram negative opportunistic pathogen capable of causing severe nosocomial infections in humans, and tobramycin is currently used to treat P. aeruginosa associated lung infections. Quorum sensing regulates biofilm formation which allows the bacterium to result in fatal infections forcing clinicians to extensively use antibiotics to manage its infections leading to emerging multiple drug resistant strains. As a result, tobramycin is also becoming resistant. Despite extensive studies on drug discovery to alleviate microbial drug resistance, the continued microbial evolution has forced researchers to focus on screening various phytochemicals and dietary compounds for antimicrobial potential. Linolenic acid (LNA) is an essential fatty acid that possesses antimicrobial actions on various microorganisms. It was hypothesized that LNA may affect the formation of biofilm on P. aeruginosa and improve the potency of tobramycin. The present study demonstrated that LNA interfered with cell-to-cell communication and reduced virulence factor production. It further enhanced the potency of tobramycin and synergistically inhibited biofilm formation through P. aeruginosa quorum sensing systems. Therefore, LNA may be considered as a potential agent for adjunctive therapy and its utilization may decrease tobramycin concentration in combined treatment thereby reducing aminoglycoside adverse effects.

Unsaturated Fatty Acids Control Biofilm Formation of Staphylococcus aureus and Other Gram-Positive Bacteria

“…A much higher concentration of 5 mg mL −1 of linoleic acid was necessary for a reduction in the biofilm formation of Pseudomonas aeruginosa and for the reported induced memory response during infection of the model host Galleria mellonella [25]. Some fatty acids such as linolenic acid combined with tobramycin were reported to interfere at higher concentrations with quorum sensing and inhibited the biofilm formation of P. aeruginosa [34]. Soni et al reported the inhibition of the quorum-sensing autoinducer-2 in their model system Vibrio harveyi BB170 by linoleic acid, oleic acid, palmitic acid and stearic acid at concentrations of 250 µm mL −1 or higher [35].…”

Combined Treatment of 6-Gingerol Analog and Tobramycin for Inhibiting Pseudomonas aeruginosa Infections

“…They identified that adjuvant interactions between analogs and antibiotics successfully reduced the production of virulence factors in P. aeruginosa by controlling the QS system. Chanda et al revealed that linoleic acid, a natural fatty acid from ginger extracts, improved the potency of tobramycin when added together in P. aeruginosa biofilms ( 41 ). They confirmed that combined treatment downregulated QS system-associated gene expression more effectively.…”

<p>Quorum Quenching: A Potential Target for Antipseudomonal Therapy</p>

“…Chanda et al 134 showed that linolenic acid and tobramycin (LNA+TOB) had significant impacts on downregulating the QS-mediated genes. Also, they have revealed that LNA+TOB therapy could inhibit motility phenotypes and reduce the development of infection.…”