Research advances in M. Tuberculosis polyketide synthase 13 inhibitors / 药学学报

Polyketide synthase 13 (Pks13) performs a critical role in the final assembly step of mycolic acid synthesis in Mycobacterium tuberculosis. The inhibition of Pks13 can influence the biosynthesis of mycolic acid, which leads to Mycobacterium tuberculosis cell death. Researchers have discovered Pks13 inhibitors with five chemical scaffolds as antituberculosis agents. Herein, we summarize recent advances in the study of Pks13 inhibitors including the process of discovery, the mechanism of action and structure-activity relationships.

Delamanid and its Role in Drug-Resistant Tuberculosis

The World Health Organisation estimates that one-third of the world's population are currently infected with Tuberculosis bacillus, 10% of whom will develop the disease at some point in their lifetime. Poverty-Stricken countries of Africa and Asia bear the brunt of the disease partly due to an ominous synergy between mycobacterium bacteria and HIV. The recent recognition of MDR-TB and strains with more complex resistance patterns has stimulated the development of new TB medications including fluoroquinolones, oxazolidinones, diarylquinolines, nitroimidazopyrans. Delamanid, a newer mycobacterial cell wall synthesis inhibitor, received a conditional approval from European medicines agency (EMA) for the treatment of MDR‑TB. Preclinical and clinical studies have shown that delamanid has high potency, least risk for drug‑drug interactions and better tolerability. The purpoe of this article is to bring forward, the various roles played by Delamanid in order to curb the problem of Multi-drug resistant Tuberculosis

Research advances on the virulence factors of Corynebacterium pseudotuberculosis / 中国人兽共患病学报

Zoonotic pathogen Corynebacterium pseudotuberculosis is the etiological agent of Caseous lymphadenitis (CLA),a chronic infectious disease throughout almost the whole world,which is extremely difficult to control.The pathogenesis of C.pseudotuberculosis is closely related to its virulence factors.In this paper,the virulence factors of C.pseudotuberculosis are reviewed,and it is proposed to further identify and analyze the roles and correlations of other different virulence factors in the pathogenesis of C.pseudotuberculosis infection,which is important for understanding the pathogenic mechanism and identify candidate vaccine of C.pseudotuberculosis.

A Novel Synthetic Mycolic Acid Inhibits Bronchial Hyperresponsiveness and Allergic Inflammation in a Mouse Model of Asthma

PURPOSE: Recognition of microbes is important to trigger the innate immune system. Mycolic acid (MA) is a component of the cell walls of mycobacteria such as Mycobacterium bovis Bacillus Calmette-Guerin. MA has immunogenic properties, which may modulate the innate and adaptive immune response. This study aimed to investigate whether a novel synthetic MA (sMA) inhibits allergic inflammatory responses in a mouse model of asthma. METHODS: BALB/c mice were injected intraperitoneally with sMA followed by sensitization and challenge with ovalbumin (OVA). Mice were examined for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells into the lung tissues, histopathological changes in the lungs and CD4+CD25+Foxp3+ T cells in the spleen, and examined the response after the depleting regulatory T cells (Tregs) with an anti-CD25mAb. RESULTS: Treatment of mice with sMA suppressed the asthmatic response, including BHR, bronchoalveolar inflammation, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment abrogated the suppressive effects of sMA in this mouse model of asthma and totally depleted CD4+CD25+Foxp3+ T cells in the spleen. CONCLUSIONS: sMA attenuated allergic inflammation in a mouse model of asthma, which might be related with CD4+CD25+Foxp3+ T cell.

Bone tuberculosis in Roman Period Pannonia (western Hungary)

The purpose of this study was to analyse a skeleton (adult female, 25-30 years) that presented evidence of tuberculous spondylitis. The skeleton, dated from the Roman Period (III-VI centuries), was excavated near the town of Győr, in western Hungary. The skeleton was examined by gross observation supplemented with mycolic acid and proteomic analyses using MALDI-TOF/TOF tandem mass spectrometry. The biomolecular analyses supported the morphological diagnosis.

Mycolic Acid Analysis for Identification of Mycobacterium spp. using High-Performance Liquid Chromatography / 대한임상병리학회지

BACKGROUND: Mycobacteria are traditionally identified with biochemical reactions. Since it takes 2 to 6 weeks, more rapid method is needed for timely treatment of mycobacterial infection. Mycolic acid analysis by high-performance liquid chromatography (HPLC) was recently introduced, which showed species-specificity with more than 95% sensitivity and 100% specificity for identifing Mycobacterium spp. within 2-4 hours. In this study, We performed mycolic acid analyses of standard strains of Mycobacterium spp. and two clinical isolates of known M. tuberculosis for demonstrating their species-specific nature and evaluated its reproduciblity. METHODS : 8 standard strains of Mycobacterium spp. (M. tuberculosis H37Rv, M. intracellurae, M. avium, M. fortuitum, M. chelonae subsp. chelonae, M. scrofulaceum, M. kansasii, M. gordonae) and 2 clinical isolates of known M. tuberculosis were analyzed. The extracted mycolic acids which were prepared by 3 steps were analyzed by HPLC with rC18 column. RESULTS: Mean retention time (MRT) of low and high molecular weight internal standards were 3.757min+/-0.017 (C.V. <0.455%) and 9.829min+/-0.015 (C.V. <0.015%), respectively (n=30). The C.V. of MRT for M. intracellurae for positive control showing double cluster pattern was less than 0.3% from 4 injection. The C.V. of MRT for M. tuberculosis H37Rv and 2 clinical isolates of M. tuberculosis with single cluster pattern were less than 0.4%, and 0.9%, respectively. The chromatographic patterns of M. kansasii and M. gordonae showed a single cluster pattern, and M. avium, M. fortuitum, M. chelonae subsp. chelonae, and M. scrofulaceum showed a double cluster pattern which were species-specific nature. CONCLUSIONS: We demonstrated HPLC method was rapid and highly reproducible.