Lysophosphatidic acid inhibition of the accumulation of Pseudomonas aeruginosa PAO1 alginate, pyoverdin, elastase and LasA

Abstract

The pathogenesis of Pseudomonas aeruginosa is at least partially attributable to its ability to synthesize and secrete the siderophore pyoverdin and the two zinc metalloproteases elastase and LasA, and its ability to form biofilms in which bacterial cells are embedded in an alginate matrix. In the present study, a lysophospholipid, 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphate [also called monopalmitoylphosphatidic acid (MPPA)], which accumulates in inflammatory exudates, was shown to inhibit the extracellular accumulation of P. aeruginosa PAO1 alginate, elastase, LasA protease and the siderophore pyoverdin. MPPA also inhibited biofilm formation. The inhibitory effects of MPPA occur independently of rpoS expression and without affecting the accumulation of the autoinducers N-(3-oxododecanoyl) homoserine lactone and N-butyryl-Lhomoserine lactone, and may be due, at least in part, to the ability of MPPA to bind divalent cations.

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“…Monopalmitoyl LPA (16:0 LPA) has been shown to inhibit virulence factor production [9] in Pseudomonas aeruginosa strains and increase the sensitivity of resistant P. aeruginosa isolates to ampicillin [10]. Monopalmitoyl LPA was found to act as a chelator, removing Ca 2+ and Mg 2+ from lipopolysaccharide found in the cell wall, consequently destabilising the outer membrane.…”

“…In addition to its reported effects on hOBs, monopalmitoyl LPA (16:0 LPA) has been reported to inhibit virulence factor production and biofilm formation of the human opportunistic pathogen Pseudomonas aeruginosa [9]. 16:0 LPA, along with several other phospholipids, e.g.…”

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“…Studies have already examined several of these factors on P. aeruginosa and staphylococcal biofilms and shown them to inhibit biofilm formation [54] and promote dissolution [55]. Multiple groups are now working to unravel the precise mechanisms of these factors and to what extent they may be used clinically to reduce bacterial infection.…”

Calcium and magnesium enhance the production of Pseudomonas aeruginosa protease IV, a corneal virulence factor

“…Production of extracellular elastase A (LasA) or LasB is enhanced by the addition of 2.5 mM calcium plus 0.1 mM zinc as compared to no added calcium plus zinc [27]. Inhibition of LasB production by a lysophospholipid can be reversed by addition of calcium, iron, magnesium, and zinc [20]. Thus, limitation or enhanced concentrations of any one of a number of nutrients or metals in the growth medium can cause a major change in the profile of extracellular enzyme production, and identical changes in the medium for two different strains can have different effects relative to the proteases produced [28].…”