Abstract Title

Investigation of alpha-toxin secretions in biofilm-conditioned medium as a potential proinflammatory disruptor to macrophages

Abstract

S. aureus biofilm infections, common in patients with chronic wounds or artificial implants, are clinically significant due to their ability to subvert the human innate immune response and to result in persistent illness. Previous investigations suggest that S. aureus biofilms attenuate macrophage-mediated antimicrobial function by disrupting NF-κB-coordinated transcription of proinflammatory intermediates. However, the identity of one or more bacterial molecules responsible for this dysfunction remains unknown. This study investigates the S. aureus-produced protein alpha toxin as a potential disruptor of the complex signaling process that leads to inflammation. In this study, antibacterial receptor agonists for TLR2, TLR9, and NOD2 are used to synthetically stimulate RAW 264.7 macrophages toward an M1 pro-inflammatory phenotype while they are co-cultured in conditioned medium from cultured wild-type or alpha toxin-knockout S. aureus biofilms. Using qPCR analysis and an NF-kB reporter assay, the pro-inflammatory response of macrophages in either environment can be quantified and compared to assess the effect of alpha toxin on one or more receptor-mediated pathways. Characterization of this host-microbe interaction can lead to a better understanding of the innate immune response, as well as to the development of targeted therapies to improve healthcare outcomes for patients with S. aureus biofilm infections.

Modified Abstract

S. aureus biofilm infections, common in patients with chronic wounds or artificial implants, are clinically significant due to their ability to subvert the human inflammatory immune response and to result in persistent illness. This study investigates the S. aureus-produced protein alpha toxin as a potential disruptor of macrophage-mediated inflammation. In this study, antibacterial receptor agonists are used to synthetically stimulate macrophages while they are co-cultured in conditioned medium from wild-type or alpha toxin-knockout S. aureus biofilms. The pro-inflammatory response of macrophages in either environment can then be quantified and compared to assess the effect of alpha toxin on several receptor-mediated pathways. Characterization of this host-microbe interaction can lead to the development of targeted therapies against S. aureus biofilm infections.

Research Category

Biomedical Sciences

Primary Author's Major

Biology

Mentor #1 Information

Dr. Min-Ho

Kim

Presentation Format

Poster

Start Date

April 2019

Research Area

Bacterial Infections and Mycoses | Immunology and Infectious Disease | Immunology of Infectious Disease | Life Sciences | Pathogenic Microbiology

This document is currently not available here.

Share

COinS
 
Apr 9th, 1:00 PM

Investigation of alpha-toxin secretions in biofilm-conditioned medium as a potential proinflammatory disruptor to macrophages

S. aureus biofilm infections, common in patients with chronic wounds or artificial implants, are clinically significant due to their ability to subvert the human innate immune response and to result in persistent illness. Previous investigations suggest that S. aureus biofilms attenuate macrophage-mediated antimicrobial function by disrupting NF-κB-coordinated transcription of proinflammatory intermediates. However, the identity of one or more bacterial molecules responsible for this dysfunction remains unknown. This study investigates the S. aureus-produced protein alpha toxin as a potential disruptor of the complex signaling process that leads to inflammation. In this study, antibacterial receptor agonists for TLR2, TLR9, and NOD2 are used to synthetically stimulate RAW 264.7 macrophages toward an M1 pro-inflammatory phenotype while they are co-cultured in conditioned medium from cultured wild-type or alpha toxin-knockout S. aureus biofilms. Using qPCR analysis and an NF-kB reporter assay, the pro-inflammatory response of macrophages in either environment can be quantified and compared to assess the effect of alpha toxin on one or more receptor-mediated pathways. Characterization of this host-microbe interaction can lead to a better understanding of the innate immune response, as well as to the development of targeted therapies to improve healthcare outcomes for patients with S. aureus biofilm infections.