Optimizing inter-microbial antagonisms to control Clostridium difficile infection The incidence of Clostridium difficile infection, which is commonly attributed to exposure to pathogenic C.difficile strains following the administration of antibiotics, has exhibited a steady rise worldwide. Recent studies suggest that clostridial infection can be controlled through promoting antagonistic inter-strain interactions on toxigenic C.difficile by non-toxigenic C.difficile and other polymicrobial strains. In order to optimize polymicrobial co-cultures for enhanced antagonistic interactions on toxigenic C.difficile strains, there is a need for means to rapidly screen for the particular microflora combinations that inhibit the colonization ability of toxigenic C.difficile strains. Since adhesion assays are time consuming, we propose the utilization of cell wall capacitance measurements as a means to rapidly screen for S-layer alterations within toxigenic C.difficile that inhibit its intestinal colonization ability. Based on this, a set of in vitro screening and in vivo validation studies are proposed for optimizing microflora towards reducing Clostridium difficile infection.

Public Health Relevance

Recent studies suggest that clostridial infection can be controlled through promoting antagonistic inter-strain interactions on toxigenic C.difficile (TCD) by polymicrobial strains, likely since the respective strains use the same colonization niche. In order to optimize polymicrobial co-cultures for enhanced antagonistic interactions on TCD strains, there is a need for means to rapidly analyze the alterations in colonization dynamics and susceptibility of TCD within a dynamic co-culture system. We propose the monitoring of C.diffcile cell wall capacitance as a rapid means to screen for the particular co-culture combinations that significantly alter the S- layer to inhibit its colonization ability.?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI130902-01
Application #
9300195
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Ranallo, Ryan
Project Start
2017-01-20
Project End
2018-12-31
Budget Start
2017-01-20
Budget End
2017-12-31
Support Year
1
Fiscal Year
2017
Total Cost
$226,715
Indirect Cost
$76,715
Name
University of Virginia
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Rohani, Ali; Moore, John H; Su, Yi-Hsuan et al. (2018) Single-cell electro-phenotyping for rapid assessment of Clostridium difficile heterogeneity under vancomycin treatment at sub-MIC (minimum inhibitory concentration) levels. Sens Actuators B Chem 276:472-480
Fernandez, Renny E; Rohani, Ali; Farmehini, Vahid et al. (2017) Review: Microbial analysis in dielectrophoretic microfluidic systems. Anal Chim Acta 966:11-33
Rohani, Ali; Sanghavi, Bankim J; Salahi, Armita et al. (2017) Frequency-selective electrokinetic enrichment of biomolecules in physiological media based on electrical double-layer polarization. Nanoscale 9:12124-12131