| Hyungjun Kim | 4 Articles |
Objectives
In this study, we performed comparative genomic and transcriptomic analysis of clinical isolates of Mycobacterium tuberculosis collected from patients with drug-susceptible tuberculosis (DS-TB). The clinical isolates were categorized based on treatment duration: standard 6 months or >6 months. Methods Study participants were recruited from a 2016 to 2018 tuberculosis cohort, and clinical M. tuberculosis isolates were collected from the sputum of patients with tuberculosis. We analyzed the genome and transcriptome of the isolated M. tuberculosis. Results Genomic analysis revealed a specific non-synonymous single-nucleotide polymorphism in pe_pgrs9 and ppe34, exclusive to the group treated for >6 months. Transcriptomic analysis revealed increased expression of various virulence-associated protein family genes and decreased expression of ribosomal protein genes and ppe38 genes in the group treated for >6 months. Conclusion The identified genetic variation and gene expression patterns may influence treatment outcomes by modulating host immune responses, increasing virulence, and potentially contributing to persister cell formation in M. tuberculosis. This study provides insights into the genetic and transcriptomic factors associated with prolonged DS-TB treatment. However, our study identified molecular characteristics using a small sample size, and further detailed studies are warranted. Citations
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Objectives
Enteroaggregative <i>Escherichia coli</i> (EAEC) was recently reported as a major diarrheagenic pathogen in infant and adult travelers, both in developing and developed countries. EAEC strains are known to be highly resistant to antibiotics including quinolones. Therefore in this study we have determined the various mechanisms of quinolone resistance in EAEC strains isolated in Korea. Methods For 26 EAEC strains highly resistant to fluoroquinolone, minimal inhibitory concentrations for fluoroquinolones were determined, mutations in the quinolone target genes were identified by PCR and sequencing, the presence of transferable quinolone resistance mechanism were identified by PCR, and the contribution of the efflux pump was determined by synergy tests using a proton pump inhibitor. The expression levels of efflux pump-related genes were identified by relative quantification using real-time PCR. Results Apart from two, all tested isolates had common mutations on GyrA (Ser83Leu and Ser87Gly) and ParC (Ser80Gln). Isolates EACR24 and EACR39 had mutations that have not been reported previously: Ala81Pro in ParC and Arg157Gly in GyrA, respectively. Increased susceptibility of all the tested isolates to ciprofloxacin and norfloxacin in the presence of the pump inhibitor implies that efflux pumps contributed to the resistance against fluoroquinolones. Expression of the efflux pump-related genes, <i>tolC</i>, <i>mdfA</i>, and <i>ydhE</i>, were induced in isolates EACR 07, EACR 29, and EACR 33 in the presence of ciprofloxacin. Conclusion These results indicate that quinolone resistance of EAEC strains mainly results from the combination of mutations in the target enzyme and an increased expression of efflux pump-related genes. The mutations Ala81Pro in ParC and Arg157Gly in GyrA have not been reported previously the exact influence of these mutations should be investigated further. Citations
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Two real-time polymerase chain reaction assays were developed to detect mutations in codons 83 and 87 in <i>gyrA</i> and in codons 80 and 91 in <i>parC</i>, the main sites that causes quinolone resistance in pathogenic <i>Escherichia coli </i>and <i>Shigella</i> spp. isolates. These assays can be employed as a useful method for controlling infections caused by quinolone-resistant <i>E coli </i>and <i>Shigella</i> isolates.
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In this study, we measured the drug resistance conferred by <i>mdfA</i> mutations in two <i>Shigella flexneri</i> strains. A mutant in <i>mdfA</i> genes was constructed by polymerase chain reaction–based, one-step inactivation of chromosomal genes. The antimicrobial susceptibility of parent and mutant strains to fluoroquinolones was determined by minimal inhibitory concentration (MICs). The <i>△mdfA</i> mutants were somewhat more susceptible to fluoroquinolones than the parent strains. The low level changes in MICs of the <i>△mdfA</i> mutants suggest that <i>mdfA</i> contributed the fluoroquinolone resistance in <i>S flexneri</i>. This finding found that the increased expression level of an MdfA efflux pump mediated fluoroquinolone resistance, but it is not likely a major effecter of higher resistance levels.
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