Inhibition of the Growth of Pathogenic Candida spp. by Salicylhydroxamic Acid

Authors: Shu-Ying Marissa Pang, Stephen Tristram, Simon Brown

Abstract:

Candida spp. are common and aggressive pathogens. Because of the growing resistance of Candida spp. to current antifungals, novel targets, found in Candida spp. but not in humans or other flora, have to be identified. The alternative oxidase (AOX) is one such possibility. This enzyme is insensitive to cyanide, but is sensitive to compounds such as salicylhydroxamic acid (SHAM), disulfiram and n-alkyl gallates. The growth each of six Candida spp. was inhibited significantly by ~13 mM SHAM or 2 mM cyanide, albeit to differing extents. In C. dubliniensis, C. krusei and C. tropicalis the rate of O2 uptake was inhibited by 18-36% by 25 mM SHAM, but this had little or no effect on C. glabrata, C. guilliermondii or C. parapsilosis. Although SHAM substantially inhibited the growth of Candida spp., it is unlikely that the inhibition of AOX was the cause. Salicylhydroxamic acid is used therapeutically in the treatment of urinary tract infections and urolithiasis, but it also has some potential in the treatment of Candida spp. infection.

Keywords: alternative oxidase, Candida spp., growth, respiration, salicylhydroxamic acid.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1079684

References:

[1] S.-Y. M. Pang, S. Tristram, and S. Brown, "Salicylhydroxamic acid inhibits the growth of Candida albicans," International Journal of Biological and Life Sciences, vol. 6, pp. 40-46, 2010.
[2] A. M. Tortorano, J. Peman, H. Bernhardt, L. Klingspor, C. C. Kibbler, O. Faure, E. Biraghi, E. Canton, K. Zimmermann, S. Seaton, and R. Grillot, "Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study," European Journal of Clinical Microbiology and Infectious Diseases, vol. 23, pp. 317-322, 2004.
[3] M. A. Pfaller, R. N. Jones, G. V. Doern, H. S. Sader, S. A. Messer, A. Houston, S. Coffman, and R. J. Hollis, "Bloodstream infections due to Candida species: SENTRY Antimicrobial Surveillance Program in North America and Latin America, 1997-1998," Antimicrobial Agents and Chemotherapy, vol. 44, pp. 747-751, 2000.
[4] O. Gudlaugsson, S. Gillespie, K. Lee, J. Vande Berg, J. Hu, S. Messer, L. Herwaldt, M. Pfaller, and D. Diekema, "Attributable mortality of nosocomial candidemia, revisited," Clinical Infectious Diseases, vol. 37, pp. 1172-1177, 2003.
[5] N. Sen and H. K. Majumder, "Mitochondrion of protozoan parasite emerges as potent therapeutic target: exciting drugs are on the horizon," Current Pharmaceutical Design, vol. 14, pp. 839-846, 2008.
[6] A. Veiga, J. D. Arrabaca, and M. C. Loueiro-Dias, "Stress situations induce cyanide-resistant respiration in spoilage yeasts," Journal of Applied Microbiology, vol. 95, pp. 364-371, 2003.
[7] V. N. Popov, R. A. Simonian, V. P. Skulachev, and A. A. Starkov, "Inhibition of the alternative oxidase stimulates H2O2 production in plant mitochondria," FEBS Letters, vol. 415, pp. 87-90, 1997.
[8] S.-Y. M. Pang, S. Tristram, and S. Brown, "An in silico model of the alternative oxidase," International Journal of Biosciences and Technology, vol. 2, pp. 139-148, 2009.
[9] R. M. Nervig and S. Kadis, "Effect of hydroxamic acids on growth and urease activity in Corynebacterium renale," Canadian Journal of Microbiology, vol. 22, pp. 544-551, 1976.
[10] C. Y. Wang and L. H. Lee, "Mutagenicity and antibacterial activity of hydroxamic acids," Antimicrobial Agents and Chemotherapy, vol. 11, pp. 753-755, 1977.
[11] L. Yan, M. Li, Y. Cao, P. Gao, Y. Cao, Y. Wang, and Y. Jiang, "The alternative oxidase of Candida albicans causes reduced fluconazole susceptibility," Journal of Antimicrobial Chemotherapy, vol. to be published, 2009.
[12] J. J. Gavin, "Analytical microbiology. II. The diffusion methods," Applied Microbiology, vol. 5, pp. 25-33, 1957.
[13] S. Budavari, "The Merck Index," 12 ed. Whitehouse Station: Merck & Co., Inc., 1996.
[14] A.-E. A. Salem and M. M. Omar, "Atomic absorption and spectrophotometric determinations of salicylhydroxamix acid in its pure and pharmeceutical dosage forms," Turkish Journal of Chemistry, vol. 27, pp. 383-393, 2003.
[15] D. H. Pincus, D. C. Coleman, W. R. Pruitt, A. A. Padhye, I. F. Salkin, M. Geimer, A. Bassel, D. J. Sullivan, M. Clarke, and V. Hearn, "Rapid identification of Candida dubliniensis with commercial yeast identification systems," Journal of Clinical Microbiology, vol. 37, pp. 3533-3539, 1999.
[16] M. B. Smith, D. Dunklee, H. Vu, and G. L. Woods, "Comparative performance of the RapID Yeast Plus System and the API 20C AUX Clinical Yeast System," Journal of Clinical Microbiology, vol. 37, pp. 2697-2698, 1999.
[17] S. Bernal, M. E. Mart├¡n, M. Garc├¡a, A. I. Aller, M. A. Mart├¡nez, and M. J. Gutiérrez, "Evaluation of CHROMagar Candida medium for the isolation and presumptive identification of species of Candida of clinical importance," Diagnostic Microbiology and Infectious Disease, vol. 24, pp. 201-204, 1996.
[18] D. Sullivan and D. Coleman, "Candida dubliniensis: characteristics and identification," Journal of Clinical Microbiology, vol. 36, pp. 329-334, 1998.
[19] R Development Core Team, "R: A language and environment for statistical computing." Vienna, Austria: R Foundation for Statistical Computing, 2006.
[20] S. Brown and N. L. Taylor, "Inhibition of mitochondrial electron transfer by antipsychotic medication," Human and Veterinary Toxicology, vol. 42, pp. 209-211, 2000.
[21] F. J. Richards, "A flexible growth function for empirical use," Journal of Experimental Botany, vol. 10, pp. 290-301, 1959.
[22] A. P. Damoglou, R. K. Buick, and M. F. Patterson, "Evaluation of different strategies for building and displaying models to describe bacterial growth in foods," IMA Journal of Mathematics Applied in Business & Industry, vol. 5, pp. 349-361, 1995.
[23] S. Brown, "Two implications of common models of microbial growth," ANZIAM Journal, vol. 49, pp. C230-C242, 2007.
[24] J. N. Siedow and A. L. Moore, "A kinetic model for the regulation of electron transfer through the cyanide-resistant pathway in plant mitochondria," Biochimica et Biophysica Acta, vol. 1142, pp. 165-174, 1993.
[25] H. Lambers, "Cyanide-resistant respiration: a non-phosphorylating electron transport pathway acting as an energy overflow," Physiologia Plantarum, vol. 55, pp. 478-485, 1982.
[26] G. G. Laties, "The cyanide-resistant, alternative path in higher plant respiration," Annual Review of Plant Physiology, vol. 33, pp. 519- 555, 1982.
[27] J. T. Bahr and W. D. Bonner, Jr., "Cyanide-insensitive respiration. II. Control of the alternate pathway," Journal of Biological Chemistry, vol. 248, pp. 3446-3450, 1973.
[28] J. B. Hiskey and V. M. Sanchez, "Mechanistic and kinetic aspects of silver dissolution in cyanide solutions," Journal of Applied Electrochemistry, vol. 20, pp. 479-487, 1990.
[29] B. K. Davis, "Diffusion in polymer gel implants," Proceedings of the National Academy of Sciences of the USA, vol. 71, pp. 3120-3123, 1974.
[30] L. Friedman, "Structure of agar gels from studies of diffusion," Journal of the American Chemical Society, vol. 52, pp. 1311-1314, 1930.
[31] N. Fatin-Rogue, K. Starchev, and J. Buffle, "Size effects on diffusion processes within agarose gels," Biophysical Journal, vol. 86, pp. 2710- 2719, 2004.
[32] E. J. Schantz and M. A. Lauffer, "Diffusion measurements in agar gel," Biochemistry, vol. 1, pp. 658-663, 1962.
[33] P. Grunwald, "Determination of effective diffusion coefficients - an important parameter for the efficiency of immobilized biocatalysts," Biochemical Education, vol. 17, pp. 99-102, 1989.
[34] R. K. Finn, "Theory of agar diffusion methods of assay," Analytical Chemistry, vol. 31, pp. 975-977, 1959.
[35] M. L. Delignette-Muller and J. P. Flandrois, "An accurate diffusion method for determining bacterial sensitivity to antibiotics," Journal of Antimicrobial Chemothrapy, vol. 34, pp. 73-81, 1994.
[36] A. L. Koch, "Diffusion through agar blocks of finite dimensions: a theoretical analysis of three systems of practical significance in microbiology," Microbiology, vol. 145, pp. 643-654, 1999.