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INVESTIGATOR: Sun, Y. Y.

PERFORMING INSTITUTION:
University of Michigan Medical School
1150 W. Medical Center Drive, 5751 Medical Sciences II
Ann Arbor, MICHIGAN 48109

TARGETING BRANCHED CHAIN FATTY ACID SYNTHESIS TO CONTROL LISTERIA CONTAMINATION IN FOOD

NON-TECHNICAL SUMMARY: Listeria is a foodborne bacterial pathogen that causes listeriosis, a disease with a wide range of clinical manifestations including gastroenteritis, meningitis and spontaneous miscarriage. According to Centers for Disease Control and Prevention, a high mortality rate of 20% has been observed with infected individuals and an even higher mortality rate was reported for early neonatal infections. Moreover, Listeria is capable of propagating in diverse food products increasing the possibility of consumer exposure. As a result, Listeria contamination has been the cause of frequent food recalls costing government agencies and food industries a tremendous amount of time and money. For example, a listeriosis outbreak in 2008 killing at least four people was linked to Listeria contamination and was the cause of one of the biggest food recalls by Maple Leaf Foods Inc. with an estimated direct cost of 19 million dollars. Therefore, it is imperative to have a better understanding of the biological mechanism adapted by Listeria to persist in food processing and storage conditions normally inhospitable to microorganisms. Using bacteriocins, which are peptides with antimicrobial activity, as food preservatives or as components in surface treatments has been proposed as methods to prevent and control Listeria contamination. However, the possibility of bacteriocin usage in enriching resistant Listeria strains and increasing Listeria virulence potential needs to be addressed in order to design more effective applications of bacteriocins. This project will address both concerns and further identify novel inhibitory compounds that can simultaneously increase Listeria susceptibility to bacteriocins and decrease pathogenicity. This proposed project will define the role of branched chain fatty acids (BCFA), which are critical membrane components in Listeria, in bacteriocin resistance; investigate how exposure to bacteriocins affect Listeria pathogenesis; and discover antimicrobial agents that specifically target BCFA production to increase the susceptibility of Listeria to bacteriocins without activating virulence. When the project is complete, we will have a better basic understanding of the role of membrane fatty acids in Listeria bacteriocin resistance, establish how bacteriocins affect Listeria virulence, and identify novel anti-Listeria compounds that can enhance the activity of bacteriocins and control the prevalent Listeria contamination. The ultimate goal of this project is to provide a fundamental understanding of molecular determinants contributing to Listeria-related food safety issues and further introduce alternative approach to eliminate Listeria contamination more efficiently during food processing and storage.

OBJECTIVES: Listeria monocytogenes (Listeria) is a food-borne pathogen with the ability to survive after prolonged storage under refrigeration conditions, and thus is a notable cause of food contamination and recall of contaminated products. Listeria infection is generally associated with serious sequelae and a high mortality rate. As a result of the high economic cost associated with recall of contaminated food products and with medical treatments, it is imperative to define resistance mechanisms used by Listeria to survive food processing and storage protocols, and to design more efficient and cost-effective strategies for remediation. Antimicrobial agents such as bacteriocins, antimicrobial peptides produced by microorganisms, have been considered as candidates for in situ or ex situ treatments to control Listeria contamination. However, the emergence of resistant Listeria strains poses a significant challenge to general applications. Moreover, the effect of these antimicrobial peptides (AMP) on Listeria virulence is poorly understood. Therefore, this study is proposed to (1) define molecular determinants providing resistance against AMP in Listeria, (2) investigate how AMP exposure affects Listeria virulence, and (3) discover chemical compounds that increase the susceptibility of Listeria to AMP without increasing virulence. Using such compounds in combination with AMP could provide a synergistic approach to control Listeria contamination more efficiently than using AMP alone. This proposed study will demand the applicant's previous experiences in environmental microbiology and provide the applicant with new training in bacterial pathogenesis with the ultimate goal of discovering novel and practical solutions to Listeria contamination in food.