Abstract
The discovery of communication systems regulating bacterial virulence hasafforded a novel opportunity to control infectious bacteria without interfering withgrowth. In this paper we describe the effect of subinhibitory concentrations of phenyl-lactic acid (PLA) on the pathogenicity of Pseudomonas aeruginosa in mice. The animalswere inoculated by oral (p.o.), intranasal (i.n.), intravenous (i.v.) and intraperitoneal (i.p.)routes with P. aeruginoasa wild and PLA-treated cultures. The mice were followed upduring 16 days after infection and the body weight, mortality and morbidity rate weremeasured every day. The microbial charge was studied by viable cell counts in lungs,spleen, intestinal mucosa and blood. The mice batches infected with wild P. aeruginosabacterial cultures exhibited high mortality rates (100 % after i.v. and i.p. route) and veryhigh cell counts in blood, lungs, intestine and spleen. In contrast, the animal batchesinfected with PLA treated bacterial cultures exhibited good survival rates (0 % mortality) and the viable cell counts in the internal organs revealed with one exception the complete abolition of the invasive capacity of the tested strains. In this study, using a mouse infection model we show that D-3-phenyllactic acid (PLA) can act as a potent antagonist of Pseudomonas (P.) aeruginosa pathogenicity, without interfering with the bacterial growth, as demonstrated by the improvement of the survival rates as well as the clearance of bacterial strains from the body.
Highlights
Upon contact with the host cells many pathogens use intercellular communication mechanisms for the regulation of virulence factors expression
In this study, using a mouse infection model we show that D-3-phenyllactic acid (PLA) can act as a potent antagonist of Pseudomonas (P.) aeruginosa pathogenicity, without interfering with the bacterial growth, as demonstrated by the improvement of the survival rates as well as the clearance of bacterial strains from the body
The present study has proved the role of subinhibitory concentrations of PLA in the attenuation of P. aeruginosa virulence and pathogenicity, using an in vivo holoxenic mouse infection experimental model
Summary
Upon contact with the host cells many pathogens use intercellular communication mechanisms for the regulation of virulence factors expression. One of the newest strategies for the prevention and treatment of bacterial infections is the inhibition of cell-to-cell signalling by inhibitors which do not interfere with the microbial growth [1]. Pseudomonas aeruginosa is an increasingly prevalent opportunistic pathogen and is the most common Gram-negative bacterium found in nosocomial and life threatening infections of immunocompromised patients [2]. The intrinsic resistance of Pseudomonas cells towards antimicrobial agents is further increased when the bacteria is growing in biofilms. Human P. aeruginosa infections involving bacterial adherence and biofilm development on medical devices are very difficult to treat and eradicate, due to their increased resistance to the anti-infective host defense [3]. The attempts made until present to attenuate bacterial pathogenesis due to P. aeruginosa by interfering with bacterial cell to cell communication, without interfering with growth have used natural antagonists produced by superior organisms (furanones) or chemically synthesized [6]
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