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

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Nov 18th, 2:15 PM Nov 18th, 3:15 PM

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