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Industrial Microbiology 2016
October 17-18, 2016
Volume 8, Issue 5(Suppl) J Microb Biochem Technol
ISSN:1948-5948 JMBT, an open access journal
conferenceseries .com
October 17-18, 2016 Kuala Lumpur, Malaysia
Industrial & Pharmaceutical MicrobiologyInternational Conference and Summit on
Georgios Daletos et al., J Microb Biochem Technol 2016, 8:5(Suppl)
Chlorflavonin, a flavone-type fungal metabolite with potent and selective antitubercular activity
Georgios Daletos, Peter Proksch, Sergi H Akone and Rainer Kalscheuer
Heinrich Heine University, Germany
Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB), is one of the leading causes of mortality and morbidity
caused by pathogenic microorganisms. Treatment of TB is currently facing serious problems due to the emergence of
multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis strains. The latter is practically untreatable
with the currently available anti-TB drugs on the market and thus that there is an urgent need for novel antibiotics against TB.
During our ongoing search for new potential anti-TB drug leads, we investigated the endophytic fungus Mucor irregularis,
which was isolated from the Cameroonian medicinal plant Moringa stenopetala . The ethyl acetate extract of M. irregularis
yielded two flavonoid-type derivatives, chlorflavonin and dechlorflavonin, the latter only differing by the absence of a
chlorine atom in the B ring. In contrast to dechlorflavonin, chlorflavonin exhibited strong growth inhibitory activity against
M. tuberculosis, indicating that chlorination plays an important role for anti-TB activity. Importantly, chlorflavonin showed
no cytotoxicity against the human fibroblast (MRC-5) and macrophage-like human acute monocytic leukemia (THP-1) cell
lines up to concentrations of 100 μM. Mapping of resistance-mediating mutations revealed that chlorflavonin specifically
inhibits the acetohydroxyacid synthase IIvB1, which mediates the first step in branched chain amino acids and pantothenic
acid biosynthesis. Chlorflavonin displayed synergistic effects in combination with the first-line antibiotic isoniazid leading to
a complete sterilization and no resistance in liquid culture during combination treatment. Moreover, chlorflavonin exhibited
potent activity against XDR M. tuberculosis strains, which highlights the potential of this compound as a promising anti-TB
agent.
Biography
Georgios Daletos obtained his Diploma and Graduate Diploma of Specialization (GDS) degrees in Pharmacy and Pharmacognosy at the University of Patras
(Greece), in 2007 and 2010, respectively. He completed his Doctorate (Ph.D.) degree in Pharmacy from the Institute of Pharmaceutical Biology and Biotechnology
(Heinrich-Heine University of Duesseldorf, Germany), in 2015, under the supervision of Professor Dr. Peter Proksch. Currently, he is a postdoctoral researcher
at the same institution. His research interest is focused on the isolation and identification of new bioactive secondary metabolites from marine invertebrates and
microorganisms.