Typhoid carriers: a Salmonella gene mutation?

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Salmonella enterica causes approximately 16 million cases of typhoid fever worldwide, killing around 500,000 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 Science, researchers at the Institute of Food Research in Norwich 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.”