Svane Simon, Lyngsie Mie C, Klitgaard Janne K, Karring Henrik
Department of Green Technology, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
Department of Biochemistry and Molecular Biology, Research Unit of Molecular Microbiology, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
Heliyon. 2024 May 14;10(10):e31209. doi: 10.1016/j.heliyon.2024.e31209. eCollection 2024 May 30.
The ability of ureolytic bacteria to break down stable urea to alkaline ammonia leads to several environmental and health challenges. Ureolytic bacteria such as and can become pathogenic and cause persistent infections that can be difficult to treat. Inhibiting urease activity can reduce the growth and pathogenicity of ureolytic bacteria. In the present study, we investigated the synergistic effects of tannic acid (TA) and the urease inhibitors fluoride (F) and acetohydroxamic acid (AHA). The concentration of AHA needed for efficient inhibition of the ureolytic activity of can be significantly reduced if AHA is coapplied with tannic acid and sodium fluoride (NaF). Thus, only 1.20 μmol l AHA in combination with 0.30 mmol l tannic acid and 0.60 mmol l NaF delayed the onset of ureolytic pH increase by 95.8 % and increased the growth lag phase by 124.3 % relative to untreated . At these concentrations, without AHA, TA and NaF increased the onset of the ureolytic pH change by only 37.0 % and the growth lag phase by 52.5 %. The strong inhibition obtained with low concentrations of AHA in triple-compound treatments suggests cobinding of F and AHA at the urease active site and could reduce the side effects of AHA when it is employed as a drug against e.g. urinary tract infections (UTIs) and blocked catheters. This study reports the basis for a promising novel therapeutic strategy to combat infections caused by ureolytic bacteria and the formation of urinary tract stones and crystalline biofilms on catheters.
尿素分解菌将稳定的尿素分解为碱性氨的能力引发了若干环境和健康挑战。诸如[具体菌名未给出]等尿素分解菌可能会致病，并导致难以治疗的持续性感染。抑制脲酶活性可降低尿素分解菌的生长和致病性。在本研究中，我们调查了单宁酸（TA）与脲酶抑制剂氟化物（F）和乙酰氧肟酸（AHA）的协同作用。如果AHA与单宁酸和氟化钠（NaF）共同应用，有效抑制[具体菌名未给出]尿素分解活性所需的AHA浓度可显著降低。因此，仅1.20 μmol·l AHA与0.30 mmol·l单宁酸和0.60 mmol·l NaF组合，相对于未处理的[具体菌名未给出]，将尿素分解导致的pH值升高的起始时间延迟了95.8%，并使生长滞后期延长了124.3%。在这些浓度下，没有AHA时，TA和NaF仅使尿素分解导致的pH值变化起始时间增加了37.0%，使生长滞后期增加了52.5%。在三化合物处理中低浓度AHA获得的强抑制作用表明F和AHA在脲酶活性位点共结合，并且当AHA用作抗例如尿路感染（UTIs）和堵塞导管的药物时，可减少其副作用。本研究报告了一种有前景的新型治疗策略的基础，该策略可对抗由尿素分解菌引起的感染以及尿路结石的形成和导管上的结晶生物膜。
