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The discovery of communication systems regulating bacterial virulence has afforded a novel opportunity to control infectious bacteria without interfering with their growth. In this paper the authors describe the effect of subinhibitory concentrations of phenyl-lactic acid (PLA) on the pathogenicity of Staphylococcus aureus in holoxenic mice. The animals were inoculated by oral (p.o.), intranasal (i.n.), intravenous (i.v.) and intraperitoneal (i.p.) routes with S. aureus wild and PLA-treated cultures. The mice were followed up during 16 days after infection and the body weight, mortality and morbidity rate were measured every day. The microbial charge was studied by viable cell counts in lungs, spleen, intestinal mucosa and blood. The present study has proved that PLA, besides its microbicidal activity, could attenuate in subinhibitory concentrations the virulence and pathogenicity of S. aureus strains, as demonstrated by in vivo holoxenic mouse infection experimental model. Our results are accounting for the hypothesis that subinhibitory concentrations of PLA, which are not affecting the bacterial cell viability, are probably interfering with the intracellular communication and the sequential and coordinated expression of different virulence factors, altering the success of this pathogen in the colonization of sensitive hosts and the development of an infectious process.

The discovery of intra- and intercellular communication systems (quorum sensing systems) regulating bacterial virulence has afforded a novel opportunity to control infectious bacteria, without interfering with their growth. In this study, we investigated the ability of subinhibitory concentrations (sIC) of phenyl lactic acid (PLA), known to be produced by Lactobacillus probiotic strains, to attenuate the virulence and pathogenicity of Pseudomonas aeruginosa (as experimental model of intercellular bacterial communication in Gram-negative bacteria) and Staphylococcus aureus (as experimental model of intercellular bacterial communication in Gram-positive bacteria) by interfering with the coordinated expression of different virulence factors implicated in the pathogenicity of these opportunistic strains. Our results showed that sIC of PLA decreased the ability of the tested strains to adhere both to the cellular and inert substrata and induced changes in the adherence patterns as well as in the cell morphology. The sIC of PLA induced a significant decrease of sheep red blood cells haemolysins, lecithinase and caseinase and stimulated lipase and gelatinase production by Pseudomonas strains. The sIC of PLA induced an important and constant increase of the Pseudomonas growth inhibition zones diameters for all tested antibiotics, demonstrating the potential use of PLA in the design of new synergic antimicrobial associations active on multiresistant and biofilm-growing P, aeruginosa strains. The present study has proved the role of sIC of PLA released by Lactobacillus probiotic strains in the attenuation of P. aeruginosa and S. aureus virulence and pathogenicity, by interfering with different processes depending on cell density and regulated by quorum sensing (i.e. growth rate, expression of adhesion molecules and secretion of soluble, enzymatic factors) and altering the success of these pathogens in the colonization of a sensitive host and the development of an infectious process. Our results demonstrate that this probiotic soluble products could be used as a new, ecological anti-infective strategy with great therapeutic and preventive value in the biomedical field (especially in the treatment of chronic infections produced by multiresistant and biofilm forming microorganisms), but also in the management of the environmental quality, agriculture and industrial field by reducing the chemical burden delivered in the external medium and by preventing the surfaces colonization with microorganisms and the development of natural biofilms.