Non-typhoidal Salmonella strains, including S. enteriditis, S. typhimurium, S. newport and S. anatum, account for 10-15% of all cases of food poisoning in North America. After an 8 to 48 h incubation period, there is a sudden onset of abdominal pain, nausea, vomiting and loose watery diarrhea. Salmonella is often found in chicken meat and eggs but salmonellosis can be prevented with proper storage, handling and cooking of chicken meat and eggs.
Typhoidal salmonella strains, S. typhi, S. paratyphi and S. choleraesuis, cause a much more serious systemic illness. Typhoid fever is characterized by a sustained fever lasting 2 to 4 weeks and bacteremia, abdominal tenderness and leukopenia. This disease is most common in the developing world where it affects 12.5 million people annually. There is no animal reservoir for these bacteria thus they rely upon fecal-oral spread. This disease can be prevented by oral and intramuscular vaccines as well as by avoiding risky foods and drinks in developing countries.
Salmonella enters host cells by inducing host cell membrane ruffling. these membrane ruffles non-specifically wrap around the bacteria and pull them into the cell. The salmonella end up in membrane-bound vesicles called salmonella-containing vacuoles (SCV). Using facs and immunofluorescence microscopy, our lab is studying the fate of these internalized bacteria and how they are trafficked to different compartments in the host cell.
The scvs are unique environments within the cell that are partially defined by the bacteria within them. as they mature, scvs do not follow the defined routes of cellular trafficking of vesicles. Our lab is interested in defining the nature of these scvs and how they differ in their composition from normal phagosomes. Using ultracentrifugation, we can separate cellular organelles from vacuoles containing bacteria to obtain purified scvs. By characterizing these scvs, we hope to determine the role that they play in salmonella infection.
While inside the host cell, salmonella also causes the rearrangement of host cell organelles to form sifs or salmonella-induced filaments. The function and significance of these novel structures is still under investigation.
Using a mouse model of infection and confocal microscopy, we can look at the role of the individual virulence genes in in vivo infections. in addition, we are studying the interplay between the bacterial virulence factors and host resistance genes. By using dna array technology, we can identify host genes that are differentially expressed following salmonella infection. with a better understanding of the host-parasite interaction, we are able to better target our therapies.
MEK and Phox pathways inhibit Salmonella replication in macrophages