Presenter Name

Haider S. Manzer

Student or Staff

Graduate/Undergraduate

Submission Type

Talk

Location

Hilton St. Petersburg Bayfront

Event Website

http://scholarcommons.usf.edu/sebasm/

Start Date

11-11-2017 8:30 AM

End Date

11-11-2017 10:00 AM

Description

The drastic rise of bacterial resistance is threatening modern medicine and human health, presenting the prospect of a post-antibiotic era in which mankind will be left defenseless against diseases that have been moderated for over half a century. In order to combat increasing resistance, it is essential to create new drugs that can inhibit the growth of multi-drug resistant pathogens. Since many current antibiotics have originated from soil dwelling microbes, there is a firm belief that a plethora of secondary metabolite biosynthesis pathways still remain undiscovered. Of these soil dwelling bacteria, the phylum Actinobacteria has served as the major source of antibacterial compounds. Environmental microbes possess an abundance of genetic material to accommodate for ever changing conditions. As such, we have established methods for the high throughput screening of Actinobacteria using a combination of epigenetic modification coupled with a variety of temperature, salinity, and pH conditions. These altered conditions allow access to undiscovered chemistry via dysregulated transcription of secondary metabolites. We have tested a wealth of crude extracts and identified many that effectively inhibit our panel of multi-drug resistant ESKAPE pathogens. An additional goal of this project is to use whole genome sequencing data to identify marker genes whose presence would indicate potential organisms for further screening. Our work represents a unique approach to an important problem, demonstrating a direct route to developing potentially new and unexplored classes of antibiotics.

Keywords: Actinobacteria, Drug Discovery, Epigenetics, Phenotypic Plasticity, Antibiotics, ESKAPE, Comparative Genomics

 
Nov 11th, 8:30 AM Nov 11th, 10:00 AM

Exploiting Phenotypic Plasticity to Unlock Cryptic Metabolic Pathways in Actinobacteria

Hilton St. Petersburg Bayfront

The drastic rise of bacterial resistance is threatening modern medicine and human health, presenting the prospect of a post-antibiotic era in which mankind will be left defenseless against diseases that have been moderated for over half a century. In order to combat increasing resistance, it is essential to create new drugs that can inhibit the growth of multi-drug resistant pathogens. Since many current antibiotics have originated from soil dwelling microbes, there is a firm belief that a plethora of secondary metabolite biosynthesis pathways still remain undiscovered. Of these soil dwelling bacteria, the phylum Actinobacteria has served as the major source of antibacterial compounds. Environmental microbes possess an abundance of genetic material to accommodate for ever changing conditions. As such, we have established methods for the high throughput screening of Actinobacteria using a combination of epigenetic modification coupled with a variety of temperature, salinity, and pH conditions. These altered conditions allow access to undiscovered chemistry via dysregulated transcription of secondary metabolites. We have tested a wealth of crude extracts and identified many that effectively inhibit our panel of multi-drug resistant ESKAPE pathogens. An additional goal of this project is to use whole genome sequencing data to identify marker genes whose presence would indicate potential organisms for further screening. Our work represents a unique approach to an important problem, demonstrating a direct route to developing potentially new and unexplored classes of antibiotics.

Keywords: Actinobacteria, Drug Discovery, Epigenetics, Phenotypic Plasticity, Antibiotics, ESKAPE, Comparative Genomics

http://scholarcommons.usf.edu/sebasm/2017/antimicrobial_therapeutics_and_resistance_1/5