A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections

Milo, S. and Heylen, R.A. and Glancy, J. and Williams, G.T. and Patenall, B.L. and Hathaway, H.J. and Thet, N.T. and Allinson, S.L. and Laabei, M. and Jenkins, A.T.A. (2021) A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections. Scientific Reports, 11 (1). ISSN 2045-2322

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Abstract

Infection and blockage of indwelling urinary catheters is significant owing to its high incidence rate and severe medical consequences. Bacterial enzymes are employed as targets for small molecular intervention in human bacterial infections. Urease is a metalloenzyme known to play a crucial role in the pathogenesis and virulence of catheter-associated Proteus mirabilis infection. Targeting urease as a therapeutic candidate facilitates the disarming of bacterial virulence without affecting bacterial fitness, thereby limiting the selective pressure placed on the invading population and lowering the rate at which it will acquire resistance. We describe the design, synthesis, and in vitro evaluation of the small molecular enzyme inhibitor 2-mercaptoacetamide (2-MA), which can prevent encrustation and blockage of urinary catheters in a physiologically representative in vitro model of the catheterized urinary tract. 2-MA is a structural analogue of urea, showing promising competitive activity against urease. In silico docking experiments demonstrated 2-MA’s competitive inhibition, whilst further quantum level modelling suggests two possible binding mechanisms.

Item Type:
Journal Article
Journal or Publication Title:
Scientific Reports
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1000
Subjects:
ID Code:
152334
Deposited By:
Deposited On:
04 Mar 2021 13:40
Refereed?:
Yes
Published?:
Published
Last Modified:
22 Nov 2021 16:13