Salmonella enteritidis Heterophil Resistance (9702755)

Egg-transmitted human salmonellosis is the most widespread food safety problem in the developed world. Over the past two decades, the number of Salmonella infections has increased dramatically in the United States, mostly due to Salmonella enteritidis var. enteritidis (SE) infections of eggs and egg products. The difficulty in controlling SE is primarily due to the low, but significant incidence of infected eggs. We have isolated two less virulent SE mutants which are only briefly shed by infected birds, are effective in protecting birds against virulent challenge, and prevent egg transmission of virulent SE. We propose to utilize these mutants to study the molecular basis of SE virulence and to identify genes involved in immune cell resistance so that safer vaccines can be developed. The following specific aims will be addressed: 1) We will complete the assessment of the SE mutants in chickens in order to assess their pattern of colonization of infected tissues and affinity for egg laying tissues; 2) The genes involved in immune cell resistance will be identified by screening complemented strains in cell cultures; 3) Mutations will be constructed in these genes in the wild type strain in order to confirm their role in immune cell resistance;and 4) The mutants will be assessed for virulence and egg transmissibility in chickens. For unknown reasons, immune cell resistance is directly linked to lowered virulence in SE. These studies will shed light on the possible mechanisms involved and add to our understanding of Salmonella pathogenesis