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thyA

thymidylate synthase A

NCBI Pathogen Isolates

Bacterial genomes carrying this gene

NCBI Reference Gene Catalog

Known alleles and reference sequences

Protein entries specific to thyA

Browse AMR rules for thyA

Validation StatusSupported

Overview

Mechanism: mutation in the thyA gene leads to resistance by disrupting the folate pathway
Validation Method: sequencing and MIC determination
Drug Classes: Para-aminosalicylic acid, Cotrimoxazole, Trimethoprim, Trimethoprim-sulfamethoxazole, Sulfamethoxazole, Pyrazinamide, PAS, Para-aminosalicyclic acid
Organisms: Mycobacterium tuberculosis, Escherichia coli LY180, Bacillus subtilis YB886, Zymomonas mobilis CP4, Haemophilus influenzae, Escherichia coli, Staphylococcus aureus, Mycobacterium tuberculosis variant bovis, Mycobacterium fortuitum subsp. fortuitum MF GZ001
Geographic Location: Australia|Peru|China, Beijing, Belarus|South Africa|South Korea|India, Brazil|Mato Grosso, China +5 more
Papers: 41
Databases: Reslit
Mutations: 94

Mutations

Protein Change	Nucleotide Change	Mechanism	Organism	Resistance To	Database	Validation Status
C161T	-	single resistance variant	Mycobacterium tuberculosis	Para-aminosalicylic acid	Card Database	Established
T202A	ACT->GCC	single resistance variant	Mycobacterium tuberculosis	Para-aminosalicylic acidPyrazinamide	Card DatabaseReslit	Confirmed

Papers41

1

Molecular genetics of para-aminosalicylic acid resistance in clinical isolates and spontaneous mutants of Mycobacterium tuberculosis.

PMID 19237648 · 2009

The study identifies mutations in the thyA gene as a cause of para-aminosalicylic acid (PAS) resistance in Mycobacterium tuberculosis, with 37% of PAS-resistant isolates having such mutations.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase A
Source Database: Reslit
Mechanism: mutation in the thyA gene leads to resistance by disrupting the folate pathway
Confers Resistance To: Para-aminosalicylic acid
Organisms Tested In: • Mycobacterium tuberculosis
Validation Method: sequencing and MIC determination

2

Mycobacterium tuberculosis thymidylate synthase gene thyX is essential and potentially bifunctional, while thyA deletion confers resistance to p-aminosalicylic acid.

PMID 22034487 · 2012

Deletion of thyA in Mycobacterium tuberculosis confers resistance to p-aminosalicylic acid (PAS). Functional analysis shows that the T202A mutation in thyA restores PAS sensitivity, whereas the V261G mutation does not.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Mechanism: p-aminosalicylic acid resistance
Organisms Tested In: • Mycobacterium tuberculosis
Validation Method: complementation studies

3

Increase in Furfural Tolerance in Ethanologenic Escherichia coli LY180 by Plasmid-Based Expression of thyA.

PMID 22504824 · 2012

The study shows that plasmid-based expression of the thyA gene from Bacillus subtilis, Escherichia coli, and Zymomonas mobilis enhances furfural tolerance in ethanologenic E. coli LY180. This improvement is attributed to increased dTMP availability for DNA repair.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Organisms Tested In: • Escherichia coli LY180
• Bacillus subtilis YB886
• Zymomonas mobilis CP4
Validation Method: plasmid-based expression and MIC testing

4

dfrA thyA Double Deletion in para-Aminosalicylic Acid-Resistant Mycobacterium tuberculosis Beijing Strains.

PMID 27021327 · 2016

Deletions in dfrA and thyA contribute to para-aminosalicylic acid resistance in Mycobacterium tuberculosis Beijing strains.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Confers Resistance To: Para-aminosalicylic acid
Organisms Tested In: • Mycobacterium tuberculosis
Geographic Location: Australia|Peru|China
Validation Method: genetic deletion and susceptibility testing

5

Inactivation of the Thymidylate Synthase thyA in Non-typeable Haemophilus influenzae Modulates Antibiotic Resistance and Has a Strong Impact on Its Interplay with the Host Airways.

PMID 28676846 · 2017

Inactivation of the thyA gene in non-typeable Haemophilus influenzae increases resistance to cotrimoxazole (TxS) and affects bacterial physiology and host interactions.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Mechanism: inactivation of the thyA gene increases TxS resistance
Confers Resistance To: Cotrimoxazole
Organisms Tested In: • Haemophilus influenzae
Geographic Location: Spain
Validation Method: generation of thyA mutants and assessment of TxS resistance

6

Machine learning and structural analysis of Mycobacterium tuberculosis pan-genome identifies genetic signatures of antibiotic resistance.

PMID 30333483 · 2018

The study identifies 33 known AMR genes and 24 new genetic signatures of AMR in Mycobacterium tuberculosis using machine learning and structural analysis. It also reveals 97 epistatic interactions across 10 resistance classes and provides mechanistic insights into the selection of these genes.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Mechanism: mutation in the gene leads to resistance to 4-aminosalicylic acid
Confers Resistance To: Para-aminosalicylic acid
Organisms Tested In: • Mycobacterium tuberculosis
Geographic Location: Belarus|South Africa|South Korea|India
Validation Method: machine learning and structural analysis

7

Evolutionary Coupling of Folate Metabolic Enzymes Reveals Adaptive Units in Bacterial Adaptation

PMID 31189117 · 2023

The study identifies DHFR and TYMS as an adaptive unit in folate metabolism, showing that mutations in these genes can confer resistance to trimethoprim through balanced metabolite concentration regulation.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Confers Resistance To: Trimethoprim
Organisms Tested In: • Escherichia coli
Validation Method: mutant plasmid construction and growth rate measurement
Sequence Accession: NC_000193

8

A biochemically-interpretable machine learning classifier for microbial GWAS.

PMID 32444610 · 2020

The study identifies pncA, ppsA, ansP2, thyA, cysK2, and katG as key genetic determinants of pyrazinamide, para-aminosalicylic acid, and isoniazid resistance in Mycobacterium tuberculosis using a metabolic allele classifier (MAC).

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Mechanism: resistant alleles decrease enzymatic activity leading to para-aminosalicylic acid resistance
Confers Resistance To: Para-aminosalicylic acid
Organisms Tested In: • Mycobacterium tuberculosis
Validation Method: flux GWAS and pathway enrichment

9

Molecular mechanisms of underlying genetic factors and associated mutations for drug resistance in Mycobacterium tuberculosis.

PMID 32573374 · 2020

The study identifies several genes and mutations associated with drug resistance in Mycobacterium tuberculosis, including katG, inhA, rpoB, embB, pncA, rpsL, rrs, gyrA, thyA, and folC, which are linked to resistance against isoniazid, ethambutol, rifampicin, streptomycin, aminoglycosides, fluoroquinolones, and para-aminosalicylic acid.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Mechanism: Mutations in thyA confer resistance to para-aminosalicylic acid (PAS)
Confers Resistance To: Para-aminosalicylic acid
Organisms Tested In: • Mycobacterium tuberculosis
Validation Method: Experimental data from the study

10

Intragenic Distribution of IS6110 in Clinical Mycobacterium tuberculosis Strains: Bioinformatic Evidence for Gene Disruption Leading to Underdiagnosed Antibiotic Resistance.

PMID 34287057 · 2021

The study identifies IS6110-mediated gene disruptions in clinical Mycobacterium tuberculosis strains that lead to resistance against bedaquiline, clofazimine, ethionamide, pyrazinamide, and para-aminosalicylic acid.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: folate-dependent thymidylate synthase
Source Database: Reslit
Confers Resistance To: Para-aminosalicylic acid
Organisms Tested In: • Mycobacterium tuberculosis
Geographic Location: South Africa|South Korea|Peru|Belarus
Validation Method: contig-based bioinformatics analysis
Sequence Accession: PRJNA739842

11

Adaptation of S. aureus towards persistence in cystic fibrosis using WGS

PMID 34578208 · 2021

The paper discusses the genetic adaptation of Staphylococcus aureus in cystic fibrosis patients, highlighting the role of horizontal gene transfer, mutations, and regulatory mechanisms in the development of persistent infections and resistance. It emphasizes the importance of whole genome sequencing in understanding the population dynamics and evolution of S. aureus in the CF airways.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: hypothetical protein
Source Database: Reslit
Mechanism: confers resistance to trimethoprim-sulfamethoxazole and the thymidine-dependent SCV phenotype
Confers Resistance To: Trimethoprim-sulfamethoxazole
Organisms Tested In: • Staphylococcus aureus
Geographic Location: Europe|United States|Germany|Austria
Validation Method: whole-genome sequencing and functional analysis

12

CGA-LMM identifies expected interactions for anti-tubercular drugs with known mechanisms

PMID 34597304 · 2021

The study identifies genes involved in resistance to anti-tubercular drugs through chemical-genetic interaction analysis, highlighting gyrA, rpoB, thyA, ino1, and kasB as key players in resistance mechanisms for fluoroquinolones, rifampin, sulfamethoxazole, and isoniazid.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: Thymidylate synthase
Source Database: Reslit
Mechanism: sulfamethoxazole resistance
Confers Resistance To: Sulfamethoxazole
Organisms Tested In: • Mycobacterium tuberculosis
Validation Method: chemical-genetic interaction analysis

13

Phenotypic and genotypic characterisation of thymine auxotrophy in Escherichia coli isolated from a patient with recurrent bloodstream infection.

PMID 35802671 · 2022

The study identifies a G172C mutation in the thyA gene, leading to thymine auxotrophy and resistance to TMP-SMX in E. coli isolates from a patient with recurrent bloodstream infections.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Mechanism: mutation leading to thymine auxotrophy
Confers Resistance To: Trimethoprim-sulfamethoxazole
Organisms Tested In: • Escherichia coli
Geographic Location: Norway
Validation Method: whole genome sequencing and growth experiments
Sequence Accession: PRJNA785617

14

Determination of critical concentration for drug susceptibility testing of Mycobacterium tuberculosis against para-aminosalicylic acid with clinical isolates with thyA, folC and dfrA mutations.

PMID 36335391 · 2022

The study identifies thyA, folC, and dfrA mutations as the primary mechanisms of para-aminosalicylic acid (PAS) resistance in Mycobacterium tuberculosis. It establishes 4 μg/ml as the critical concentration for distinguishing PAS-susceptible and resistant isolates.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Mechanism: mutational resistance
Confers Resistance To: Para-aminosalicylic acid
Organisms Tested In: • Mycobacterium tuberculosis
Geographic Location: Beijing
Validation Method: whole genome sequencing and MIC testing
Sequence Accession: CNP0002824

15

Genomic analysis of Mycobacterium tuberculosis variant bovis strains isolated from bovine in the state of Mato Grosso, Brazil.

PMID 36467663 · 2022

The study identified multiple AMR genes and mutations in Mycobacterium tuberculosis variant bovis strains from Mato Grosso, Brazil, including resistance to pyrazinamide, isoniazid, rifampicin, streptomycin, ethambutol, ethionamide, fluoroquinolones, kanamycin, capreomycin, paraminosalicylic acid, cycloserine, bedaquiline, linezolid, and delamanid.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: paraminosalicylic acid resistance
Source Database: Reslit
Confers Resistance To: Para-aminosalicylic acid
Organisms Tested In: • Mycobacterium tuberculosis variant bovis
Geographic Location: Brazil|Mato Grosso
Validation Method: genomic analysis
Sequence Accession: SRR15649877|SRR15649878|SRR15649879|SRR15649880|SAMN21018175|SAMN21018176|SAMN21018177|SAMN21018178|JAIOHE000000000|JAIOHF000000000|JAIOHG000000000|JAIOHH000000000|ERR3445501|ERR3445502|ERR3445503|ERR3445504|SRR10997360|SRR10997362|SRR10997361|SRR13046675|SRR12511761|SRR9850830

16

Comparative genome analysis reveals high-level drug resistance markers in a clinical isolate of Mycobacterium fortuitum subsp. fortuitum MF GZ001.

PMID 36683685 · 2022

The study identifies multiple drug resistance markers in the clinical isolate of Mycobacterium fortuitum subsp. fortuitum MF GZ001, including mutations in genes such as rpoB, katG, AAC(2')-Ib, gyrA, gyrB, embB, pncA, thyA, embC, embR, and iniA, which confer resistance to various antibiotics.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Mechanism: mutated
Confers Resistance To: Trimethoprim
Organisms Tested In: • Mycobacterium fortuitum subsp. fortuitum MF GZ001
Geographic Location: China
Validation Method: genomic analysis and mutation detection
Sequence Accession: CP107719|SRR22164027

17

Whole genome sequencing reveals candidate genes involving in PAS resistance in M. Tuberculosis isolated from patients in Thailand.

PMID 38057660 · 2024

The study identified mutations in thyA, thyX, folC, and ribD genes, along with intergenic regions, that contribute to PAS resistance in M. tuberculosis. These mutations were validated through complementation assays and MIC testing.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Mechanism: mutations in thyA confer resistance to PAS by altering the enzyme's function, reducing the effectiveness of PAS in inhibiting thymidylate synthesis.
Confers Resistance To: Para-aminosalicylic acid
Organisms Tested In: • Mycobacterium tuberculosis
Geographic Location: Thailand
Validation Method: complementation assay and MIC testing
Sequence Accession: PRJNA390471

18

Evolutionary trajectory of bacterial resistance to antibiotics and antimicrobial peptides in Escherichia coli.

PMID 40013796 · 2025

The study reveals that E. coli develops resistance to antibiotics faster than to antimicrobial peptides (AMPs). Trimethoprim-resistant E. coli with mutations in the thyA gene shows increased susceptibility to pexiganan.

Gene Information

Gene Name: thyA
Allele: thyA
Encodes: thymidylate synthase
Source Database: Reslit
Confers Resistance To: Trimethoprim
Organisms Tested In: • Escherichia coli
Validation Method: CRISPRi gene expression repression and MIC testing