ArticleNature communications2022
Host-dependent resistance of Group A Streptococcus to sulfamethoxazole mediated by a horizontally-acquired reduced folate transporter.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 24 citations in OpenAlex.
- Emerging roles of pterins as signaling molecules in bacteria.Biochemical Society transactions · 2026Review
- Dynamics of the Microbiome and Antibiotic Resistome in Hyper-Mesophilic Anaerobic Digestion of Cattle Manure Assisted with Granular Activated Carbon.ACS environmental Au · 2026Article
- Macrolide resistance trajectories across threeFrontiers in microbiology · 2026Article
- Impact of Host and Bacterial Metabolism on Antibiotic Susceptibility.Biochemistry · 2025Review
- Diversity and antimicrobial resistance among bacterial isolates from finfish aquaculture in Thailand.BMC veterinary research · 2025Article
- Antimicrobial Susceptibility Profiles ofAntibiotics (Basel, Switzerland) · 2025Article
- Acquired Bacterial Resistance to Antibiotics and Resistance Genes: From Past to Future.Antibiotics (Basel, Switzerland) · 2025Review
- The burden of group AiScience · 2025Review
- An energy coupling factor transporter ofbioRxiv : the preprint server for biology · 2024Article
- Expulsion mechanism of the substrate-translocating subunit in ECF transporters.Nature communications · 2023Article
- Pathogenesis, epidemiology and control of Group A Streptococcus infection.Nature reviews. Microbiology · 2023Review
- Group A streptococcal (GAS) infections amongst children in Europe: Taming the rising tide.New microbes and new infections · 2023Article
- Innovative Strategies to Overcome Antimicrobial Resistance and Tolerance.Microorganisms · 2022Review
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Authors and funding
22 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Described antimicrobial resistance mechanisms enable bacteria to avoid the direct effects of antibiotics and can be monitored by in vitro susceptibility testing and genetic methods. Here we describe a mechanism of sulfamethoxazole resistance that requires a host metabolite for activity. Using a combination of in vitro evolution and metabolic rescue experiments, we identify an energy-coupling factor (ECF) transporter S component gene (thfT) that enables Group A Streptococcus to acquire extracellular reduced folate compounds. ThfT likely expands the substrate specificity of an endogenous ECF transporter to acquire reduced folate compounds directly from the host, thereby bypassing the inhibition of folate biosynthesis by sulfamethoxazole. As such, ThfT is a functional equivalent of eukaryotic folate uptake pathways that confers very high levels of resistance to sulfamethoxazole, yet remains undetectable when Group A Streptococcus is grown in the absence of reduced folates. Our study highlights the need to understand how antibiotic susceptibility of pathogens might function during infections to identify additional mechanisms of resistance and reduce ineffective antibiotic use and treatment failures, which in turn further contribute to the spread of antimicrobial resistance genes amongst bacterial pathogens.
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