Why Do Microbes Kill Some People but Not Others?

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The brain-eating amoeba Naegleria fowleri is back in the news. This nightmare-inducing parasite weasels its way into the brain via the nose, which is why the microbe is often associated with people swimming in lakes. Once in the brain, N. fowleri brings about a meningoencephalitis that is almost 100% fatal.

The silver lining is that infections are very, very rare. According to the CDC, "There have been 31 reported infections in the U.S. in the 10 years from 2003 to 2012, despite millions of recreational water exposures each year." [Emphasis added.]

In that statistic lies one of the greatest mysteries of medical microbiology. Why do some horrible infectious diseases kill an unlucky few and ignore millions of others? Perhaps the most infamous example is Typhoid Mary, a woman who infected approximately 51 people with Salmonella Typhi, though she herself never got sick. Also, did you know that some people are completely resistant to HIV infection? Lucky. SNP_260x260.jpg

For these people, their favorable fortune is tied to genetics. Increasingly, evidence suggests that the genes we carry around may be just as important in determining the outcome of an infection as the genes the microbes carry around.

A new study published in BMC Immunology hammers this point home with an analysis of susceptibility to the 2009 pandemic H1N1 influenza A virus. Chinese researchers examined single base differences (called "single nucleotide polymorphisms" or SNPs) in the sequences of two genes called IL1A and IL1B, both of which encode a protein important in inflammation. By comparing SNPs in people who became infected with those who did not, the researchers were able to show that some genetic variants were linked with a higher risk of contracting influenza.

For example, the authors found that a single base change (from G to T) located at a particular position in the IL1A gene appeared to double a person's risk of becoming infected with influenza. This mutation is responsible for changing the amino acid at this location from serine to alanine. Thus, changing one amino acid in one protein appears to be enough to alter how a person responds to the influenza virus.

When scientists and medical doctors speak of "personal genomics," this is the sort of data they are talking about. It is easy to envision, at some point in the future, that your genome sequence would be able to predict the infectious and non-infectious diseases to which you are particularly susceptible.

Source:  Yingxia Liu, Shaoyuan Li, Guoliang Zhang, Guang Nie, Zhizhong Meng, Dongting Mao, Chang Chen, Xinchun Chen, Boping Zhou and Gucheng Zeng. "Genetic variants in IL1A and IL1B contribute to the susceptibility to 2009 pandemic H1N1 influenza A virus." BMC Immunology 14 (37). Published: 8 August 2013. doi:10.1186/1471-2172-14-37

(Image: Broad Institute)

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