ABSTRACT
Skin biopsies from US leprosy patients were tested for mutations associated with drug resistance. Dapsone resistance was found in 4 of 6 biopsies from American Samoa patients. No resistance was observed in patients from other origins. The high rate of dapsone resistance in patients from American Samoa warrants further investigation.
Subject(s)
Dapsone/therapeutic use , Drug Resistance, Bacterial/genetics , Genes, Bacterial , Leprostatic Agents/therapeutic use , Leprosy/drug therapy , Mycobacterium leprae/drug effects , Mycobacterium leprae/genetics , American Samoa , Biopsy , Clofazimine/therapeutic use , Drug Administration Schedule , Humans , Leprosy/diagnosis , Leprosy/microbiology , Microbial Sensitivity Tests , Mutation , Mycobacterium leprae/classification , Mycobacterium leprae/isolation & purification , Rifampin/therapeutic use , Skin/drug effects , Skin/microbiologyABSTRACT
Mycobacterium lepromatosis, an independent species from Mycobacterium leprae, has been found to be a causative agent for diffuse lepromatous leprosy (DLL) in Mexico, but remains poorly studied. Here, the drug resistance-determining regions (DRDR) of folP1, rpoB and gyrA (conferring resistance to dapsone, rifampicin and quinolone, respectively) in M. lepromatosis from leprosy patients in Mexico were characterized. No mutations or silent mutations were found at previously characterized major sites in DRDR of M. lepromatosis. However, a non-synonymous mutation was found in codon 54 between two major sites of the folP1 DRDR in M. lepromatosis sequences. All M. lepromatosis isolates showed CAG sequence in codon 54 of folP1. Because the next codons 53 and 55 are known as major mutation sites for drug resistance, more detailed analysis using more samples is needed to determine whether it influences susceptibility to dapsone and/or efficiency of folate biosynthesis in M. lepromatosis or not.
Subject(s)
Drug Resistance, Bacterial/genetics , Leprosy, Lepromatous/microbiology , Mycobacterium/genetics , Adolescent , Adult , Aged , Base Sequence , Child , Female , Humans , Male , Mexico , Middle Aged , Molecular Sequence Data , Sequence Analysis, DNA , Young AdultABSTRACT
The combination of trimethoprim (TMP) and sulfamethoxazole (SMX) has been shown to be active against Mycobacterium tuberculosis (Mtb) in clinical tuberculosis (TB) treatment. However, the mechanism of action of TMP-SMX against Mtb is still unknown. To unravel this, we have studied the effect of TMP and SMX by deleting the folP2 gene in Mycobacterium smegmatis (Msm), and overexpressing the Mtb and Msm folP1/2 genes in Msm. Knocking out of the folP2 gene in Msm reduced the minimum inhibitory concentration of SMX 8-fold compared with wild type. Overexpression of the folP1 genes from Mtb and Msm increased the MICs by 4- and 2-fold in Msm for SMX and TMP, respectively. We show a strong correlation between the expression of folP1 and folP2 genes and TMP-SMX resistance in mycobacteria. This suggests that a combination of FolP2 inhibitor and SMX could be used for TB treatment with a better outcome.
Subject(s)
Antitubercular Agents/pharmacology , Genes, Bacterial , Mycobacterium smegmatis/drug effects , Sulfamethoxazole/pharmacology , Trimethoprim/pharmacology , Gene Deletion , Gene Expression , Microbial Sensitivity Tests , Mycobacterium smegmatis/genetics , Mycobacterium tuberculosis/geneticsABSTRACT
The emergence of multiple drug resistant Mycobacterium leprae has emphasized the need for early decision of effective antileprosy drug in the treatment for leprosy patients. Mutations in the genes associated with multiple drug resistance in Mycobacterium leprae isolates from 17 South Korean patients, who were already confirmed to have mutations in folP1 gene, were investigated using a PCR - single strand conformation polymorphism (SSCP) - DNA sequencing assay. Two strains, which has double mutations, were found in the two unrelated patients : one missense mutation in folP1 (Arg 55 for Pro) and in rpoB (Gly 522 for Ser), and in folP1 (Ala 53 for Thr) and in gyrB (Asn 426 for Asp), respectively. The patients were treated with the long monotheraphy of dapsone or with the inappropriate regimen of antileprosy drugs. These results emphasize the importance of multi-drug theraphy in order to prevent mult-idrug resistance and assist in the choice of the appropriate regimens for treating leprosy.
