Enteric (typhoid) fever caused by salmonella species is frequently fatal in man, domestic animals, and rodents. Salmonella serotypes and species exhibit a high degree of host specificity in their ability to cause enteric fever (Salmonella typhi, man; S. derby, cattle; S. pullorum, poultry, and S. enteritidis and S. typhimurium, mice). In the mouse Ity is the major genetic locus affecting salmonella resistance during the first two weeks following oral or parenteral infection. This is accomplished primarily by Ity control of the rate of intracellular growth of salmonella in the liver and spleen of infected mice. Ity has been reported to also affect resistance to intracellular infections with Mycobacterium bovis, Mycobacterium lepraemurium, and Leishmania donovani, but not a number of other intracellular and extracellular pathogens. The mechanism by which Ity controls intracellular growth rates is not known. The salmonella gene mviA(vir) is necessary for certain salmonella to exploit the Ity(s) (susceptible) genotype, but has little or no effect on the growth of salmonella in Ity(r) (resistant) mice. Knowledge of the mechanism of action of mviA should not only provide insight into mechanisms used by salmonella to grow in the host, but may also reveal the mechanism of action of Ity. We have identified a restriction site into which the insertion of antibiotic resistance cassettes blocks mviA function. We have demonstrated that avirulence is the result of a functional mviA(avir) and that insertion of an antibiotic resistance cassette into mviA(avir) results in virulence. From the proposed studies we hope to obtain detailed knowledge about the mviA gene and the nature of its gene product (MviA), and its mechanism of action. We will also continue ongoing studies to identify nutrients and pathways that limit the growth of mviA(vir) and mviA(avir) salmonella in Ity(r) and Ity(s )mice. Anything we learn about rate limiting in vivo growth factors will add to our knowledge of the micro-environment of growing salmonella and should contribute to our studies of mviA and Ity mechanisms, and visa versa. The results of the proposed studies should contribute to our understanding of the regulation of intracellular growth rates of not only salmonella, but certain other intracellular pathogens.

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National Institute of Allergy and Infectious Diseases (NIAID)
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Bacteriology and Mycology Subcommittee 2 (BM)
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University of Alabama Birmingham
Schools of Dentistry
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Berkow, R L; Schlabach, L; Dodson, R et al. (1993) In vivo administration of the anticancer agent bryostatin 1 activates platelets and neutrophils and modulates protein kinase C activity. Cancer Res 53:2810-5
Benjamin Jr, W H; Yother, J; Hall, P et al. (1991) The Salmonella typhimurium locus mviA regulates virulence in Itys but not Ityr mice: functional mviA results in avirulence;mutant (nonfunctional) mviA results in virulence. J Exp Med 174:1073-83
Dunlap, N E; Benjamin Jr, W H; McCall Jr, R D et al. (1991) A 'safe-site' for Salmonella typhimurium is within splenic cells during the early phase of infection in mice. Microb Pathog 10:297-310
Benjamin Jr, W H; Hall, P; Briles, D E (1991) A hemA mutation renders Salmonella typhimurium avirulent in mice, yet capable of eliciting protection against intravenous infection with S. typhimurium. Microb Pathog 11:289-95
Fallon, M T; Benjamin Jr, W H; Schoeb, T R et al. (1991) Mouse hepatitis virus strain UAB infection enhances resistance to Salmonella typhimurium in mice by inducing suppression of bacterial growth. Infect Immun 59:852-6
Benjamin Jr, W H; Hall, P; Roberts, S J et al. (1990) The primary effect of the Ity locus is on the rate of growth of Salmonella typhimurium that are relatively protected from killing. J Immunol 144:3143-51
Fallon, M T; Schoeb, T R; Benjamin Jr, W H et al. (1989) Modulation of resistance to Salmonella typhimurium infection in mice by mouse hepatitis virus (MHV). Microb Pathog 6:81-91
Benjamin Jr, W H; Turnbough Jr, C L; Goguen, J D et al. (1986) Genetic mapping of novel virulence determinants of Salmonella typhimurium to the region between trpD and supD. Microb Pathog 1:115-24
Yother, J; McDaniel, L S; Briles, D E (1986) Transformation of encapsulated Streptococcus pneumoniae. J Bacteriol 168:1463-5
Briles, D E; Horowitz, J; McDaniel, L S et al. (1986) Genetic control of the susceptibility to pneumococcal infection. Curr Top Microbiol Immunol 124:103-20

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