School of Mathematical and Natural Sciences, Arizona State University at the West Campus, Phoenix, AZ, USA.
Lett Appl Microbiol. 2014 Jan;58(1):31-41. doi: 10.1111/lam.12153. Epub 2013 Sep 23.
Urease is a virulence factor for the Gram-positive urinary tract pathogen Staphylococcus saprophyticus. The susceptibility of this enzyme to chemical inhibition was determined using soluble extracts of Staph. saprophyticus strain ATCC 15305. Acetohydroxamic acid (Ki = 8.2 μg ml(-1) = 0.106 mmol l(-1) ) and DL-phenylalanine hydroxamic acid (Ki = 21 μg ml(-1) = 0.116 mmol l(-1) ) inhibited urease activity competitively. The phosphorodiamidate fluorofamide also caused competitive inhibition (Ki = 0.12 μg ml(-1) = 0.553 μmol l(-1) = 0.000553 mmol l(-1) ), but the imidazole omeprazole had no effect. Two flavonoids found in green tea extract [(+)-catechin hydrate (Ki = 357 μg ml(-1) = 1.23 mmol l(-1) ) and (-)-epigallocatechin gallate (Ki = 210 μg ml(-1) = 0.460 mmol l(-1) )] gave mixed inhibition. Acetohydroxamic acid, DL-phenylalanine hydroxamic acid, fluorofamide, (+)-catechin hydrate and (-)-epigallocatechin gallate also inhibited urease activity in whole cells of strains ATCC 15305, ATCC 35552 and ATCC 49907 grown in a rich medium or an artificial urine medium. Addition of acetohydroxamic acid or fluorofamide to cultures of Staph. saprophyticus in an artificial urine medium delayed the increase in pH that normally occurs during growth. These results suggest that urease inhibitors may be useful for treating urinary tract infections caused by Staph. saprophyticus.
The enzyme urease is a virulence factor for the Gram-positive urinary tract pathogen Staphylococcus saprophyticus. We have shown that urease activity in cell-free extracts and whole bacterial cells is susceptible to inhibition by hydroxamates, phosphorodiamidates and flavonoids, but not by imidazoles. Acetohydroxamic acid and fluorofamide in particular can temporarily delay the increase in pH that occurs when Staph. saprophyticus is grown in an artificial urine medium. These results suggest that urease inhibitors may be useful as chemotherapeutic agents for the treatment of urinary tract infections caused by this micro-organism.
脲酶是革兰氏阳性尿路上皮病原体腐生葡萄球菌的毒力因子。使用腐生葡萄球菌菌株 ATCC 15305 的可溶性提取物确定了该酶对化学抑制的敏感性。乙酰氧肟酸（Ki = 8.2 μg ml（-1）= 0.106 mmol l（-1））和 DL-苯丙氨酸羟肟酸（Ki = 21 μg ml（-1）= 0.116 mmol l（-1））竞争性抑制脲酶活性。磷酰胺基氟酰胺也引起竞争性抑制（Ki = 0.12 μg ml（-1）= 0.553 μmol l（-1）= 0.000553 mmol l（-1）），但咪唑奥美拉唑没有效果。绿茶提取物中发现的两种类黄酮[（+）-儿茶素水合物（Ki = 357 μg ml（-1）= 1.23 mmol l（-1））和（-）-表没食子儿茶素没食子酸酯（Ki = 210 μg ml（-1）= 0.460 mmol l（-1））]产生混合抑制。乙酰氧肟酸、DL-苯丙氨酸羟肟酸、氟酰胺、（+）-儿茶素水合物和（-）-表没食子儿茶素没食子酸酯也抑制了在丰富培养基或人工尿液培养基中生长的 ATCC 15305、ATCC 35552 和 ATCC 49907 菌株的全细胞脲酶活性。在人工尿液培养基中向腐生葡萄球菌培养物中添加乙酰氧肟酸或氟酰胺可延迟生长过程中通常发生的 pH 值升高。这些结果表明，脲酶抑制剂可能可用于治疗腐生葡萄球菌引起的尿路感染。
酶脲酶是革兰氏阳性尿路上皮病原体腐生葡萄球菌的毒力因子。我们已经表明，无细胞提取物和全细菌细胞中的脲酶活性易受羟肟酸、磷酰胺基和类黄酮的抑制，但不受咪唑的抑制。特别是乙酰氧肟酸和氟酰胺可以暂时延迟腐生葡萄球菌在人工尿液培养基中生长时发生的 pH 值升高。这些结果表明，脲酶抑制剂可能可作为化学治疗剂，用于治疗该微生物引起的尿路感染。
