Abstract
Despite Pseudomonas aeruginosa antibiotic resistance, erythromycin (ERM, a macrolide) at subinhibitory concentration (sub-MIC) reduces its pathogenicity. We assessed ERM effects on P. aeruginosa in cultures containing choline (Ch) without and with 1% ethanol (Et) addition. Ch, as an osmoprotectant, increases the following virulence factors (VIFs): lectins (haemagglutination); proteases (casein and elastin lysis); haemolytic phospholipase C (PLC-H; haemolysis); pyocyanin (pigment o.d.) and autoinducers (violacein bioassay). Ethanol also increases lectins, proteases, pyocyanin, autoinducers and rhamnolipid (RHAL; haemolysis) formation, but reduces Ch-induced PLC and protease (elastase) activities. ERM has been shown to totally suppress the Et-induced VIFs, whereas partially reducing the Ch-induced ones. Unexpectedly, ERM combination with 1% Et dramatically annuls the Ch-induced factors. Et contribution might be attributed to its effect on cell membrane, displaying synergism with ERM, whereas antagonizing Ch osmoprotective potential and shifting gene expression. This information is worth further molecular investigation and clinical consideration for skin infection therapy.
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References
Chen A, Innis S, Davidson A, James S . (2005). Phosphatidylcholine and lysophosphatidylcholine excretion is increased in children with cystic fibrosis and is associated with plasma homocysteine, S-adenosylhomocysteine, and S-adenosylmethionine. Am J Clin Nutr 81: 686–691.
DeVault J, Kimbara K, Chakrabarty A . (1990). Pulmonary dehydration and infection in cystic fibrosis: evidence that ethanol activates alginate gene expression and induction of mucoidy in Pseudomonas aeruginosa. Mol Microbiol 4: 737–745.
Diggle S, Stacey R, Dodd C, Camara M, Williams P, Winzer K . (2006). The galactophilic lectin, LecA, contributes to biofilm development in Pseudomonas aeruginosa. Environ Microbiol 8: 1095–1104.
Essar D, Eberly L, Hadero A, Crawford I . (1990). Identification and characterization of genes for a second anthranilate synthase in Pseudomonas aeruginosa: interchangeability of the two anthranilate synthases and evolutionary implications. J Bacteriol 172: 884–900.
Fujii T, Kadota J, Kawakami K, Iida K, Shirai R, Kaseda M et al. (1995). Long term effect of erythromycin therapy in patients with chronic Pseudomonas aeruginosa infection. Thorax 50: 1246–1252.
Gilboa-Garber N . (1982). Pseudomonas aeruginosa lectins. Methods Enzymol 83: 378–385.
Gilboa-Garber N, Garber N . (1989). Microbial lectin cofunction with lytic activities as a model for a general basic lectin role. FEMS Microbiol Rev 63: 211–221.
Gilboa-Garber N, Zakut V, Mizrahi L . (1973). Production of cholinesterase by Pseudomonas aeruginosa, its regulation by glucose and cyclic AMP and inhibition by antiserum. Biochim Biophys Acta 297: 120–124.
Imamura Y, Higashiyama Y, Tomono K, Izumikawa K, Yanagihara K, Ohno H et al. (2005). Azithromycin exhibits bactericidal effects on Pseudomonas aeruginosa through interaction with the outer membrane. Antimicrob Agents Chemother 49: 1377–1380.
Imberty A, Wimmerova M, Mitchell E, Gilboa-Garber N . (2004). Structures of the lectins from Pseudomonas aeruginosa: insight into the molecular basis for host glycan recognition. Microbes Infect 6: 221–228.
Jensen S, Phillippe L, Teng Tseng J, Stemke G, Campbell J . (1980). Purification and characterization of exocellular proteases produced by a clinical isolate and a laboratory strain of Pseudomonas aeruginosa. Can J Microbiol 26: 77–86.
Katri N, Gilboa-Garber N . (2007). Ethanol effects on Pseudomonas aeruginosa lectin, protease, hemolysin, pyocyanin, autoinducer and phosphatase levels depending on medium composition and choline presence. Curr Microbiol 54: 296–301.
Kita E, Sawaki M, Oku D, Hamuro A, Mikasa K, Konishi M et al. (1991). Suppression of virulence factors of Pseudomonas aeruginosa by erythromycin. J Antimicrob Chemother 27: 273–284.
Kobayashi H . (1995). Biofilm disease: Its clinical manifestation and therapeutic possibilities of macrolides. Am J Med 99: S26–S30.
Kudoh S, Azuma A, Yamamoto M, Izumi T, Ando M . (1998). Improvement of survival in patients with diffuse panbronchiolitis treated with low-dose erythromycin. Am J Respir Crit Care Med 157: 1829–1832.
Matsufuji M, Nakata K, Yoshimoto A . (1997). High production of rhamnolipids by Pseudomonas aeruginosa growing on ethanol. Biotechnol Lett 19: 1213–1215.
McClean K, Winson M, Fish L, Taylor A, Chhabra S, Camara M et al. (1997). Quorum sensing and Chromobacterium violaceum: exploitation of violacein production and inhibition for the detection of N-acylhomoserine lactones. Microbiology 143: 3703–3711.
Sage A, Vasil M . (1997). Osmoprotectant-dependent expression of plcH, encoding the hemolytic phospholipase C, is subject to novel catabolite repression control in Pseudomonas aeruginosa PAO1. J Bacteriol 179: 4874–4881.
Sofer D, Gilboa-Garber N, Belz A, Garber N . (1999). ‘Subinhibitory’ erythromycin represses production of Pseudomonas aeruginosa lectins, autoinducer and virulence factors. Chemotherapy 45: 335–341.
Tielker D, Hacker S, Loris R, Strathmann M, Wingender J, Wilhelm S et al. (2005). Pseudomonas aeruginosa lectin LecB is located in the outer membrane and is involved in biofilm formation. Microbiology 151: 1313–1323.
Wagner V, Frelinger J, Barth R, Iglewski B . (2006). Quorum sensing: dynamic response of Pseudomonas aeruginosa to external signals. Trends Microbiol 14: 55–58.
Winzer K, Falconer C, Garber NC, Diggle S, Camara M, Williams P . (2000). The Pseudomonas aeruginosa lectins PA-IL and PA-IIL are controlled by quorum sensing and by RpoS. J Bacteriol 182: 6401–6411.
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This study is a part of N Katri's (née Melamed) PhD thesis at Bar-Ilan University, 2003. We thank Ms Sharon Victor and Ms Ela Gindy for their great help in the preparation of the manuscript and graphic presentation.
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Katri, N., Garber, N., Kilfin, G. et al. Abrogation of the resistance of choline-induced Pseudomonas aeruginosa virulence to sub-MIC erythromycin by ethanol. ISME J 2, 1243–1246 (2008). https://doi.org/10.1038/ismej.2008.79
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DOI: https://doi.org/10.1038/ismej.2008.79
