Class
Article
College
College of Engineering
Department
Biological Engineering Department
Faculty Mentor
Jixun Zhan
Presentation Type
Poster Presentation
Abstract
More than two billion people were infected by the bacterial pathogen Mycobacterium tuberculosis (Mtb) in 2020. However, during the past 50 years, the first-line (isoniazid, delamanid, and rifampicin) and second-line (capreomycin, streptomycin, and cycloserine) therapies have remained unchanged with disadvantages such as long treatment periods and severe side effects. The slow development of anti-TB drugs cannot combat the fast development of drug resistant M. tuberculosis strains from multidrug-resistant (MDR) into extensively drug resistant (XDR), which further hinders the World Health Organization’s goal to end the global TB pandemic by the year 2035. Flavonoids are a type of natural product with various biological activities. Although flavonoids are predominately identified from plants, several filamentous fungal species were also reported to produce novel bioactive flavonoids, such as chlorflavonin. Chlorflavonin exhibited significant in vitro inhibitory activity against Mtb. More interestingly, chlorflavonin showed synergistic effects with the first-line antibiotics isoniazid and delamanid on intracellular activity against infected human macrophages, which is better than streptomycin. Unfortunately, low water-solubility of flavonoids often hinders their bioavailability. Glycosylation is an effective method to enhance their polarity and then alter physicochemical properties. This work focuses on the development of novel water-soluble chlorflavonin derivatives to combat the threat of drug-resistant tuberculosis. In this study, we successfully increased the production titer of expensive chlorflavonin (100 USD/5 mg) from Aspergillus candidus NRRL 5214. Next, chlorflavonin-5-O-β-D-glucuronide was produced from chlorflavonin via Streptomyces chromofuscus ATCC 49982. The water solubility was increased around 27 times from 4.38 ± 0.54 mg/L to 117.86 ± 4.81 mg/L. This study provides an efficient method to create water-soluble analogs of chlorflavonin for anti-TB drug development.
Location
Logan, UT
Start Date
4-11-2023 10:30 AM
End Date
4-11-2023 11:30 AM
Glycosylation of Anti-TB Agent Chlorflavonin for Combating Mycobacterium Tuberculosis
Logan, UT
More than two billion people were infected by the bacterial pathogen Mycobacterium tuberculosis (Mtb) in 2020. However, during the past 50 years, the first-line (isoniazid, delamanid, and rifampicin) and second-line (capreomycin, streptomycin, and cycloserine) therapies have remained unchanged with disadvantages such as long treatment periods and severe side effects. The slow development of anti-TB drugs cannot combat the fast development of drug resistant M. tuberculosis strains from multidrug-resistant (MDR) into extensively drug resistant (XDR), which further hinders the World Health Organization’s goal to end the global TB pandemic by the year 2035. Flavonoids are a type of natural product with various biological activities. Although flavonoids are predominately identified from plants, several filamentous fungal species were also reported to produce novel bioactive flavonoids, such as chlorflavonin. Chlorflavonin exhibited significant in vitro inhibitory activity against Mtb. More interestingly, chlorflavonin showed synergistic effects with the first-line antibiotics isoniazid and delamanid on intracellular activity against infected human macrophages, which is better than streptomycin. Unfortunately, low water-solubility of flavonoids often hinders their bioavailability. Glycosylation is an effective method to enhance their polarity and then alter physicochemical properties. This work focuses on the development of novel water-soluble chlorflavonin derivatives to combat the threat of drug-resistant tuberculosis. In this study, we successfully increased the production titer of expensive chlorflavonin (100 USD/5 mg) from Aspergillus candidus NRRL 5214. Next, chlorflavonin-5-O-β-D-glucuronide was produced from chlorflavonin via Streptomyces chromofuscus ATCC 49982. The water solubility was increased around 27 times from 4.38 ± 0.54 mg/L to 117.86 ± 4.81 mg/L. This study provides an efficient method to create water-soluble analogs of chlorflavonin for anti-TB drug development.