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Genetic mutation determines type of Salmonella infection


Researchers have discovered a genetic mutation in the typhoid fever bacterium that allows the organism to establish persistent infections in mice. The mutation results in a greater production of the virulence proteins necessary to infect host cells. The finding suggests that a single protein may be critical in determining whether an infected individual develops a short-term illness or becomes a carrier of the disease.

Citizens in Laredo, Texas, receive typhoid vaccinations in 1954.

Typhoid fever occurs almost exclusively in developing countries and can be treated with antibiotics. Left untreated, however, the disease can persist for several months and sometimes becomes chronic. Chronic carriers experience no symptoms beyond their initial illness, but the bacteria remain in their cells. Controlling typhoid fever is difficult in part because carriers are unaware that they are 'shedding' live Salmonella enterica bacteria. Some 16 million new infections occur per year.

Mark O. Clements, of the Karolinska Institute in Stockholm, Sweden, and colleagues set out to understand the genetics of typhoid fever infections. They analyzed two forms of the bacterium in mice—one that causes the acute disease, and another that produces carriers. In the gene that codes for PNPase (polynucleotide phosphorylase), they discovered a single-letter mutation that shortens the protein.

Microarray analysis showed that PNPase mutants expressed more virulence factor proteins; these proteins help the bacterium trick host cells into internalizing the organism. Once inside the host cell, the bacterium relies on the proteins to reproduce.

The scientists concluded that PNPase normally represses the expression of virulence factor proteins, so mutant strains reproduce faster and more efficiently than normal strains. PNPase mutants may be better able to resist the host organism's immune system and establish themselves permanently, making the infected individual a carrier. The findings are published in Proceedings of the National Academy of Sciences.

The healthy carrier state, which occurs in five percent of typhoid fever patients, made its first United States appearance in an Irish immigrant named Mary Mallon, better known as 'Typhoid Mary.' A food service worker, Mallon broke out of forced isolation in 1907 and caused several typhoid outbreaks. She infected 47 people with the disease, three of whom died.

Although she is often depicted as a malicious villain, Mallon may never have received an adequate explanation for why she was confined. She probably acted unintentionally, unable to believe that she could feel healthy and still spread a disease.

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Clements, M.O. et al. Polynucleotide phosphorylase is a global regulator of virulence and persistency in Salmonella enterica. Proc Natl Acad Sci USA 99, 8784-8789 (June 25, 2002).

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