A5034892971- Antibiotic Resistance in Bacteria
- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- DNA Repair Mechanisms
- Bacterial Genetics and Biotechnology
- Infectious Diseases and Tuberculosis
- Drug Transport and Resistance Mechanisms
- Inflammasome and immune disorders
- Oral microbiology and periodontitis research
Duke University
2023-2025
Cornell University
2018-2023
Kettering University
2021-2023
DNA repair systems allow microbes to survive in diverse environments that compromise chromosomal integrity. Pathogens such as Mycobacterium tuberculosis must contend with the genotoxic host environment, which generates mutations underlie antibiotic resistance. Mycobacteria encode widely distributed SOS pathway, governed by LexA repressor, but also PafBC, a positive regulator of transcriptional damage response (DDR). Although outputs these have been characterized, their full functional...
Abstract Antibiotic resistance of Mycobacterium tuberculosis is exclusively a consequence chromosomal mutations. Translesion synthesis (TLS) widely conserved mechanism DNA damage tolerance and mutagenesis, executed by translesion polymerases such as DinBs. In mycobacteria, DnaE2 the only known agent TLS role DinB unknown. Here we demonstrate that, when overexpressed, DinB1 promotes missense mutations conferring to rifampicin, with mutational signature distinct from that DnaE2, abets...
Tuberculosis (TB) outcomes vary widely, from asymptomatic infection to mortality, yet most animal models do not recapitulate human phenotypic and genotypic variation. The genetically diverse Collaborative Cross mouse panel distinct facets of TB disease that occur in humans allows identification genomic loci underlying clinical outcomes. We previously mapped a susceptibility locus on chromosome 2. Here, we identify cathepsin Z ( Ctsz ) as lead candidate this show ablation leads increased...
Translesion synthesis by translesion polymerases is a conserved mechanism of DNA damage tolerance. In bacteria, DinB enzymes are the widely distributed promutagenic polymerases. The role DinBs in mycobacterial mutagenesis was unclear until recent studies revealed for DinB1 substitution and frameshift mutagenesis, overlapping with that polymerase DnaE2. Mycobacterium smegmatis encodes two additional (DinB2 DinB3) tuberculosis DinB2, but roles these tolerance unknown. biochemical properties...
ABSTRACT Antibiotic resistance of Mycobacterium tuberculosis is exclusively a consequence chromosomal mutations. Translesion synthesis (TLS) widely conserved mechanism DNA damage tolerance and mutagenesis, executed by translesion polymerases such as DinBs. In mycobacteria, DnaE2 the only known agent TLS role DinB unknown. Here we demonstrate that mycobacterial DinB1 abets insertion deletion frameshift mutagenesis in homo-oligonucleotide runs. primary mediator spontaneous −1 mutations runs...
Abstract DNA repair systems allow microbes to survive in diverse environments that compromise chromosomal integrity. Pathogens such as M. tuberculosis must contend with the genotoxic host environment, which generates mutations underlie antibiotic resistance. Mycobacteria encode widely distributed SOS pathway, governed by LexA repressor, but also PafBC, a positive regulator of transcriptional damage response (DDR). Although outputs these have been characterized, their full functional division...
ABSTRACT Translesion synthesis mediated by translesion polymerases is a conserved mechanism of DNA damage tolerance. In bacteria, DinB enzymes are widely distributed promutagenic polymerases. The role DinBs in mycobacterial mutagenesis was unclear until recent studies revealed for DinB1 substitution and frameshift mutagenesis, overlapping with that polymerase DnaE2. M. smegmatis encodes two additional (DinB2 DinB3) tuberculosis DinB2, but the roles these tolerance unknown. biochemical...