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

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A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections. / Milo, S.; Heylen, R.A.; Glancy, J.; Williams, G.T.; Patenall, B.L.; Hathaway, H.J.; Thet, N.T.; Allinson, S.L.; Laabei, M.; Jenkins, A.T.A.

In: Scientific Reports, Vol. 11, No. 1, 3726, 12.02.2021.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

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Milo, S, Heylen, RA, Glancy, J, Williams, GT, Patenall, BL, Hathaway, HJ, Thet, NT, Allinson, SL, Laabei, M & Jenkins, ATA 2021, 'A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections', Scientific Reports, vol. 11, no. 1, 3726. https://doi.org/10.1038/s41598-021-83257-2

APA

Milo, S., Heylen, R. A., Glancy, J., Williams, G. T., Patenall, B. L., Hathaway, H. J., Thet, N. T., Allinson, S. L., Laabei, M., & Jenkins, A. T. A. (2021). A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections. Scientific Reports, 11(1), [3726]. https://doi.org/10.1038/s41598-021-83257-2

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Milo, S. ; Heylen, R.A. ; Glancy, J. ; Williams, G.T. ; Patenall, B.L. ; Hathaway, H.J. ; Thet, N.T. ; Allinson, S.L. ; Laabei, M. ; Jenkins, A.T.A. / A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections. In: Scientific Reports. 2021 ; Vol. 11, No. 1.

Bibtex

@article{f88636f88a5e49ab8d3444ec22a2a8e9,
title = "A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections",
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{\textquoteright}s competitive inhibition, whilst further quantum level modelling suggests two possible binding mechanisms.",
author = "S. Milo and R.A. Heylen and J. Glancy and G.T. Williams and B.L. Patenall and H.J. Hathaway and N.T. Thet and S.L. Allinson and M. Laabei and A.T.A. Jenkins",
year = "2021",
month = feb,
day = "12",
doi = "10.1038/s41598-021-83257-2",
language = "English",
volume = "11",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections

AU - Milo, S.

AU - Heylen, R.A.

AU - Glancy, J.

AU - Williams, G.T.

AU - Patenall, B.L.

AU - Hathaway, H.J.

AU - Thet, N.T.

AU - Allinson, S.L.

AU - Laabei, M.

AU - Jenkins, A.T.A.

PY - 2021/2/12

Y1 - 2021/2/12

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-021-83257-2

DO - 10.1038/s41598-021-83257-2

M3 - Journal article

VL - 11

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 3726

ER -