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Change In One Base Pair Can Create A Typhoid Mary

Salmonella enterica causes approximately 16 million cases of typhoid fever worldwide, killing around 500,000 people per year.

One in thirty of the survivors, however, become carriers, such as Typhoid Mary, who caused several typhoid outbreaks in New York City at the beginning of the last century.

In carriers, the bacteria remain hidden inside cells and the gall bladder, causing new infections as they are shed from an apparently healthy host.

The factors that enable the bacteria to establish chronic infection were unclear.

However, in a paper published this week in the Proceedings of the National Academy of Sciences, researchers at the Institute of Food Research in Norwich, UK, and the Karolinska Institute in Sweden found that the change of a single base pair in one Salmonella gene can determine if the bacteria cause short-term illness or a long-term carrier state.

The authors stumbled upon the striking change in infectivity while investigating a mutant strain that produces persistent infection in mice.

Tracing the mutation to the genome, the scientists found it caused a single base change in the gene coding for the enzyme polynucleotide phosphorylase (PNPase).

This enzyme normally decreases the production of virulence factors by breaking down the messenger RNA essential for the translation of the genetic code into the Salmonella virulence factors. The mutant enzyme is less active, allowing greater production of virulence factors and, therefore, persistent infection.

Dr. Jay Hinton of the Institute of Food Research said, “This is a new mechanism for controlling the expression of Salmonella virulence factors, and it's the first time that this type of gene regulation has been linked with the carrier state of typhoid.”

The mission of the Institute of Food Research is to carry out independent basic and strategic research on food safety, quality, nutrition and health. It is a company limited by guarantee, with charitable status, grant aided by the UK Biotechnology and Biological Sciences Research Council (BBSRC). The Institute is based in the Norwich Research Park.

(Reference: Mark O. Clements, Sofia Eriksson, Arthur Thompson, Sacha Lucchini, Jay C.D. Hinton, Staffan Normark, and Mikael Rhen (2002). Polynucleotide phosphorylase is a global regulator of virulence and persistency in Salmonella enterica. Proceedings of the National Academy of Sciences.)

Related websites:

Proceedings of the National Academy of Sciences

More about Typhoid Mary

More about typhoid fever

Institute of Food Research

Karolinska Institute






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