The rpoB gene encodes the β subunit of RNA polymerase holoenzyme in Mycobacterium leprae (M. leprae). Missense mutations in the rpoB gene were identified as etiological factors for rifampin resistance in leprosy. In the present study, we identified mutations corresponding to rifampin resistance in relapsed leprosy cases from three hospitals in southern India which treat leprosy patients. DNA was extracted from skin biopsies of 35 relapse/multidrug therapy non-respondent leprosy cases, and PCR was performed to amplify the 276 bp rifampin resistance-determining region of the rpoB gene. PCR products were sequenced, and mutations were identified in four out of the 35 cases at codon positions D441Y, D441V, S437L and H476R. The structural and functional effects of these mutations were assessed in the context of three-dimensional comparative models of wild-type and mutant M. leprae RNA polymerase holoenzyme (RNAP), based on the recently solved crystal structures of RNAP of Mycobacterium tuberculosis, containing a synthetic nucleic acid scaffold and rifampin. The resistance mutations were observed to alter the hydrogen-bonding and hydrophobic interactions of rifampin and the 5′ ribonucleotide of the growing RNA transcript. This study demonstrates that rifampin-resistant strains of M. leprae among leprosy patients in southern India are likely to arise from mutations that affect the drug-binding site and stability of RNAP.
We reported an unusual case of a 26-year-old man presenting to surgical emergency as generalized peritonitis following an ingestion of multiple metallic sewing needles. The X-ray of his abdomen showed pneumoperitoneum and multiple metallic foreign bodies in the abdominal cavity. An ultrasonogram of his abdomen showed multiple metallic foreign bodies in the abdominal cavity and urinary bladder. Emergency exploratory laparotomy was performed. On laparotomy, gastric and duodenal perforation was found through which metallic sewing needles were protruding out. A peritoneal lavage was done, and all the sewing needles were extracted from the perforation site, paracolic gutter, liver parenchyma, and urinary bladder. The primary repair of the perforation with omental patching was done with the drainage of subhepatic space and pelvic cavity. These multiple ingested sewing needles led to the perforation of the stomach and the duodenum, which resulted in perforation peritonitis.
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