Reversal of activity of trimethoprim against Gram-positive cocci by thymidine, thymine and ‘folates’

Hamilton-Miller, J. M. T.

doi:10.1093/jac/22.1.35

Cited by 49Antimicrobial Resistance in StaphylococcusAntibiotic Resistance in BacteriaBacterial Genetics and Biotechnology

Reversal of activity of trimethoprim against Gram-positive cocci by thymidine, thymine and ‘folates’

Hamilton-Miller, J. M. T.·1988·Journal of Antimicrobial Chemotherapy

DOI 10.1093/jac/22.1.35

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Abstract

The reversal of the antibacterial activity of trimethoprim against different species of Gram-positive cocci (Staphylococcus aureus, Staph. epidermidis, Staph. saprophyticus, group B streptococci, Streptococcus faecalis and Str. faecium) by thymine, thymidine and various 'folates' (folate, folinate, dihydrofolate and tetrahydrofolate) was tested. Against group B streptococci and staphylococci only thymidine antagonized trimethoprim. However, for enterococci, thymine, thymidine, dihydrofolate, tetrahydrofolate and folinate all reversed the activity of trimethoprim, although by different amounts. Dihydrofolate was significantly more effective as a trimethoprim antagonist for Str. faecium than for Str. faecalis. While thymine and thymidine caused the MIC of trimethoprim against enterococci to increase more than 100-fold--thereby rendering them resistant--the 'folates' brought about much smaller increases in trimethoprim MIC, in the order of ten-fold only. Thus, even in the presence of 'folates' enterococci remain sensitive in vitro to trimethoprim.

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Enterococci can use another bypass strategy by incorporating exogenous tetrahydrofolic acid and folinic acid when these are added to the media, and this ability is correlated with up to a 25-fold increase in TMP-SMX MICs and is thought to impair antimicrobial activity in vivo.
“Interestingly, enterococci use another “bypass” strategy by incorporating exogenous tetrahydrofolic acid and folinic acid when added to the media. This ability to use folate from different sources is correlated with up to 25-fold increase in the MICs of TMP-SMX and are thought to impair the antimicrobial activity in vivo (84, 85).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [84]

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Authors: Hamilton-Miller, J. M. T.
Affiliations: Royal Free London NHS Foundation Trust (GB)
Corresponding author: Hamilton-Miller, J. M. T.
Venue: Journal of Antimicrobial Chemotherapy
Publisher: Oxford University Press (OUP)
Published: 1988
Volume: 22
Issue: 1
Pages: 35-39
ISSN: 0305-7453 (ISSN-L)
1460-2091
DOI: 10.1093/jac/22.1.35
OpenAlex: W2158908237
Cited by: 49
References: 0
Citations by year: 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 1 · 2016: 2 · 2015: 2 · 2014: 4 · 2012: 1
FWCI: 2.42
Type: journal article
Language: en
Open access: closed
Locations: Journal of Antimicrobial Chemotherapy (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords: trimethoprim, Gram-positive cocci, thymidine, thymine, folic acid, dihydrofolate, tetrahydrofolate, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus agalactiae, Enterococcus faecalis, Enterococcus faecium, Enterococcus, antimicrobial susceptibility, minimum inhibitory concentration
MeSH terms: Folic Acid, Microbial Sensitivity Tests, Staphylococcus, Streptococcus, Thymidine, Thymine, Trimethoprim

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Reversal of activity of trimethoprim against Gram-positive cocci by thymidine, thymine and ‘folates’

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