Increased Susceptibility of Mycobacterium tuberculosis to Ethionamide by Expressing PPs-Induced Rv0560c

Tuberculosis, an infectious disease, is one of the leading causes of death worldwide. Drug-resistant tuberculosis exacerbates its threat. Despite long-term and costly treatment with second-line drugs, treatment failure rates and mortality remain high. Therefore, new strategies for developing new drugs and improving the efficiency of existing drug treatments are urgently needed. Our research team reported that PPs, a new class of potential anti-tuberculosis drug candidates, can inhibit the growth of drug-resistant Mycobacterium tuberculosis. Here, we report a synergistic effect of PPs with ethionamide (ETH), one of the second-line drugs, as a result of further research on PPs. While investigating gene expression changes based on microarray and 2DE (two-dimensional gel electrophoresis), it was found that PPs induced the greatest overexpression of Rv0560c in M. tuberculosis. Based on this result, a protein microarray using Rv0560c protein was performed, and it was confirmed that Rv0560c had the highest interaction with EthR, a repressor for EthA involved in activating ETH. Accordingly, a synergistic experiment was conducted under the hypothesis of increased susceptibility of ETH to M. tuberculosis by PPs. As a result, in the presence of 0.5× MIC PPs, ETH showed a growth inhibitory effect on drug-sensitive and -resistant M. tuberculosis even at a much lower concentration of about 10-fold than the original MIC of ETH. It is also suggested that the effect was due to the interaction between PPs and Rv2887, the repressor of Rv0560c. This effect was also confirmed in a mouse model of pulmonary tuberculosis, confirming the potential of PPs as a booster to enhance the susceptibility of M. tuberculosis to ETH in treating drug-resistant tuberculosis. However, more in-depth mechanistic studies and extensive animal and clinical trials are needed in the future

Characteristics and Microbiome Profiling of Korean Gochang Bokbunja Vinegar by the Fermentation Process

As NGS (next-generation sequencing) technology develops, metagenomics-based microbial ecology, that is, microbiome research, has recently led to the science of fermented food. Based on the above technology, a study was conducted to understand the characteristics of vinegar made from bokbunja, a local crop in Gochang-gun, Korea. Physicochemical characteristics of vinegar, organic acid analysis, microbial community analysis, and electronic tongue analysis were explored while fermenting the vinegar for 70 days under eight fermentation conditions according to the concentration of bokbunja liquid (100% or 50%), type of fermenter (porcelain jar or stainless container), and fermentation environment (natural outdoor conditions or temperature/oxygen controlled). As a result, distinct microbial community patterns were found in the stage of acetic acid fermentation and, accordingly, this fermentation of Gochang vinegar is classified into three categories. Vinegar prepared by the traditional method of outdoor fermentation using jars showed characteristics of “Acetobacter (42.1%)/Lactobacillus (56.9%) fusion fermentation”. Under conditions where oxygen and temperature were controlled indoors using jars, characteristics of “Komagataeibacter (90.2%) fermentation” were found. “Lactobacillus (92.2%) fermentation” characteristics were discovered under natural outdoor conditions using stainless steel containers. These fermentation pattern differences were related to taxonomic phylogenetic diversity, which was also considered involved in determining organic acid production and taste. These results will be helpful as a scientific basis for understanding the fermentation characteristics of Gochang vinegar and developing high-value-added traditional vinegar products