Presentation Title
The antimicrobial peptides HNP-1 and HBD-2 act against Mycobacterium smegmatis independent from their chirality
Faculty Mentor
Edith Porter
Start Date
18-11-2017 2:15 PM
End Date
18-11-2017 3:15 PM
Location
BSC-Ursa Minor 69
Session
Poster 3
Type of Presentation
Poster
Subject Area
biological_agricultural_sciences
Abstract
Background: Tuberculosis is one of the top 10 causes of death worldwide causing 1.4 million deaths in 2015. Mycobacterium tuberculosis (Mtb), the predominant cause of tuberculosis, is an acid-fast rod-shaped aerobic bacterium with a lipid-rich cell wall. One of the first lines of defense against Mtb is found in the innate immune response involving the release of antimicrobial peptides (AMPs) by epithelial cells and phagocytes. AMPs such as defensins are amphipathic molecules that can integrate into bacterial phospholipid membranes and may be useful in the fight against Mtb which has developed multi-drug resistance. Preliminary data has shown growth inhibition of the model organism Mycobacterium smegmatis (Ms) in the presence of L-Human Beta Defensin-2 (L-HBD-2) and L-Human Neutrophil Peptide-1 (L-HNP-1). We hypothesized that L-HNP-1 and L-HBD-2 inhibit Ms growth due to membrane-targeted action which would be independent from their chirality. Objective: This study aimed to compare growth inhibitory effects of the D- and L- forms of HBD-2 and HNP-1 against Ms. Methods: Homogenized 48 h cultures of Ms were incubated in 7H9 broth with serially diluted AMPs (0.3125-5 µM final concentration) or solvent control for up to 48 h and metabolic activity was quantified by reduction of the resazurin dye. Results: D- and L forms of HNP-1 and HBD-2 both inhibited Ms growth throughout all tested concentrations. Conclusion: This data supports that L-HNP-1 and L-HBD-2 have a membrane targeted action and do not appear to act through a receptor. Acknowledgements: Wuyuan Lu for peptide synthesis.
Keywords: antimicrobial peptides, defensins, tuberculosis, membrane, mycolic acid, mucosa, stereochemistry
The antimicrobial peptides HNP-1 and HBD-2 act against Mycobacterium smegmatis independent from their chirality
BSC-Ursa Minor 69
Background: Tuberculosis is one of the top 10 causes of death worldwide causing 1.4 million deaths in 2015. Mycobacterium tuberculosis (Mtb), the predominant cause of tuberculosis, is an acid-fast rod-shaped aerobic bacterium with a lipid-rich cell wall. One of the first lines of defense against Mtb is found in the innate immune response involving the release of antimicrobial peptides (AMPs) by epithelial cells and phagocytes. AMPs such as defensins are amphipathic molecules that can integrate into bacterial phospholipid membranes and may be useful in the fight against Mtb which has developed multi-drug resistance. Preliminary data has shown growth inhibition of the model organism Mycobacterium smegmatis (Ms) in the presence of L-Human Beta Defensin-2 (L-HBD-2) and L-Human Neutrophil Peptide-1 (L-HNP-1). We hypothesized that L-HNP-1 and L-HBD-2 inhibit Ms growth due to membrane-targeted action which would be independent from their chirality. Objective: This study aimed to compare growth inhibitory effects of the D- and L- forms of HBD-2 and HNP-1 against Ms. Methods: Homogenized 48 h cultures of Ms were incubated in 7H9 broth with serially diluted AMPs (0.3125-5 µM final concentration) or solvent control for up to 48 h and metabolic activity was quantified by reduction of the resazurin dye. Results: D- and L forms of HNP-1 and HBD-2 both inhibited Ms growth throughout all tested concentrations. Conclusion: This data supports that L-HNP-1 and L-HBD-2 have a membrane targeted action and do not appear to act through a receptor. Acknowledgements: Wuyuan Lu for peptide synthesis.
Keywords: antimicrobial peptides, defensins, tuberculosis, membrane, mycolic acid, mucosa, stereochemistry