Two anti-mycobacterial peptides with a lasso structure, named lariatins A and B, were separated by HP-20 and ODS column chromatographies and purified by HPLC from the culture broth of Rhodococcus jostii K01-B0171, which was isolated from soil aggregates collected in Yunnan, China. Lariains A and B showed growth inhibition against Mycobacterium smegmatis with MIC values of 3.13 and 6.25 m g/ml in agar dilution method, respectively. Furthermore, lariatin A inhibited the growth of Mycobacterium tuberculosis with an MIC of 0.39 mg/ml in liquid microdilution method.Keywords lariatin A, lariatin B, lasso structure, antimycobacterial peptide, tuberculosis, Rhodococcus jostii, soil aggregates
IntroductionOur research group has focused on discovery of antiinfectives from microbial metabolites [1ϳ3]. Tuberculosis (TB) is still the greatest single infectious cause of mortality in the world, together with HIV and malaria [4]. Moreover, the spread of the HIV promoted to increase the number of tuberculosis patients [5]. However, powerful anti-TB drugs with a new mechanism of action have not been developed in last over thirty years, and only 5 anti-TB drugs can be clinically used still now. Since isoniazid and ethambutol, first-line anti-TB drugs, show specific inhibition against Mycobacteria, we have screened for new agents from microbial metabolites having specific inhibition against Mycobacterium smegmatis among 16 test microorganisms including Gram-positive and -negative bacteria, fungi and yeasts. As a part of this program, we discovered novel