Inhibition of the Growth of Pathogenic Candida spp. by Salicylhydroxamic Acid
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.
[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. Martín, M. García, A. I. Aller, M. A. Martínez, 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.
[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. Martín, M. García, A. I. Aller, M. A. Martínez, 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.
@article{"International Journal of Biological, Life and Agricultural Sciences:61723", author = "Shu-Ying Marissa Pang and Stephen Tristram and Simon Brown", title = "Inhibition of the Growth of Pathogenic Candida spp. by Salicylhydroxamic Acid", 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.", volume = "4", number = "1", pages = "109-7", }
