Publications by authors named "S Modlin"
Article Synopsis
- Five new or repurposed drugs for multi-drug resistant tuberculosis were approved recently, but resistance to these drugs developed quickly, potentially due to existing resistance in the bacteria prior to treatment.
- A study analyzed 409 clinical bacterial samples to find new and existing genetic variants associated with drug resistance, discovering 5 known and 67 novel resistance variants in 13 genes.
- The results showed that 21% of the samples had preexisting mutations that could lead to drug resistance, mainly due to mutations affecting drug activation and efflux mechanisms, raising concerns about how these mutations arose and their implications for future treatments.
Here, we describe a clinical case of pyrazinamide-resistant (PZA-R) tuberculosis (TB) reported as PZA-susceptible (PZA-S) by common molecular diagnostics. Phenotypic susceptibility testing (pDST) indicated PZA-R TB. Targeted Sanger sequencing reported wild-type PncA, indicating PZA-S TB.
View Article and Find Full Text PDFPoint mutations in the gene and the promoter are known to confer resistance to the second-line injectable drugs (SLIDs) amikacin (AMK), capreomycin (CAP), and kanamycin (KAN). While mutations in these canonical genes confer the majority of SLID resistance, alternative mechanisms of resistance are not uncommon and threaten effective treatment decisions when using conventional molecular diagnostics. In total, 1,184 clinical Mycobacterium tuberculosis isolates from 7 countries were studied for genomic markers associated with phenotypic resistance.
View Article and Find Full Text PDFPyrazinamide (PZA) plays a crucial role in first-line tuberculosis drug therapy. Unlike other antimicrobial agents, PZA is active against Mycobacterium tuberculosis only at low pH. The basis for this conditional drug susceptibility remains undefined.
View Article and Find Full Text PDFAccurate and timely functional genome annotation is essential for translating basic pathogen research into clinically impactful advances. Here, through literature curation and structure-function inference, we systematically update the functional genome annotation of Mycobacterium tuberculosis virulent type strain H37Rv. First, we systematically curated annotations for 589 genes from 662 publications, including 282 gene products absent from leading databases.
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