AbstractObjectivespara-Aminosalicylic acid is an antifolate prodrug activated in the folate biosynthesis pathway of Mycobacterium tuberculosis (Mtb), ultimately inhibiting dihydrofolate reductase encoded by dfrA. Mutations in dfrA coding and upstream regions have not been thoroughly investigated. This study aimed to assess mutations in dfrA and its upstream regulatory region in clinical Mtb isolates.MethodsWe retrieved and analysed 6547 whole-genome sequences of Mtb clinical isolates. We identified 29 SNPs in the dfrA coding region and eight mutations in the thyA–dfrA upstream region. The most prevalent coding mutations and upstream mutations were selected for functional evaluation using thermal stability analysis, GFP reporter assays and para-aminosalicylic acid drug susceptibility test (DST).ResultsThe coding mutations Trp142→Gly, Gln28→Leu and Arg32→Pro were analysed for protein thermal stability and para-aminosalicylic acid susceptibility. Gln28→Leu showed increased thermal stability relative to the WT, whereas Trp142→Gly and Arg32→Pro exhibited reduced stability. Consistently, para-aminosalicylic acid DST demonstrated that Gln28→Leu conferred an 8-fold increase in para-aminosalicylic acid resistance, while Trp142→Gly and Arg32→Pro remained phenotypically susceptible. Moreover, GFP reporter assays revealed that G70T, G59T and C48A increased promoter activity by 13-fold, 4-fold and 3-fold, respectively, whereas the remaining mutations showed no significant effect. Findings were verified by para-aminosalicylic acid DST, where G70T, G59T and C48A showed para-aminosalicylic acid resistance compared with WT.ConclusionsBy integrating genomic analysis with functional assays of thermal stability, promoter activity and drug susceptibility, this study demonstrated that mutations in dfrA coding and upstream regulatory regions contribute to para-aminosalicylic acid resistance in Mtb clinical isolates.

Salmonella enterica subspecies enterica serovar Infantis carrying the blaCTX-M-65 gene has been increasingly detected globally, including in South Korea, since 2022. We analyzed 65 blaCTX-M-65–positive Salmonella Infantis isolates from humans, poultry, and wastewater collected during 2022–2024 by using whole-genome sequencing and phylogenomic analysis. All isolates were multidrug resistant, commonly to aminoglycosides, β-lactams, quinolones, tetracyclines, amphenicols, and folate pathway inhibitors. Phylogenetic analysis revealed high genetic similarity among isolates from humans, poultry, and wastewater, which were intermingled within monophyletic clades with high bootstrap support, indicating close genomic relatedness across sectors. Bayesian phylogeographic reconstruction suggested multiple potential introductions during 2018–2022, including 1 lineage related to isolates from the United States (clade I) and others related to isolates from the United Kingdom (clade II). Those findings highlight the emergence and genomic diversity of blaCTX-M-65–positive Salmonella Infantis in South Korea and support the value of continued genomic surveillance across sectors.

L’equilibrio resiste per i primi quindici minuti, poi Rossotono Mesagne comincia a vivere di folate.... L'articolo Basket B2/M, Virtus Mesagne: vittoria davanti al proprio pubblico con la Virtus Molfetta proviene da Antenna Sud.

Curate Feeds | Make Collections | Customize Email Briefs

Curate Feeds | Make Collections | Customize Email Briefs

Curate Feeds | Make Collections | Customize Email Briefs

Learn the benefits of eating kiwi skin, from extra fiber and antioxidants to more vitamin C, vitamin E, and folate in every bite.

葉酸が多い食品をランキング形式で紹介。100gあたりの含有量と1食分の目安量で比較。文科省食品成分データベース準拠。