Genetic changes attenuated Salmonella’s virulence, potentially enabling the bacteria to cause chronic infections in humans.
Article published in The-Scientist magazine, May 28, 2024
To uncover Salmonella’s tricks to persist, Ashlee Earl, a microbiologist at the Broad Institute, teamed up with Ohad Gal-Mor, a molecular microbiologist at the Tel Aviv University who studies Salmonella pathogenesis. Salmonellosis is a notifiable disease in Israel, meaning that health providers are required to report to government health authorities when they identify someone with it. For almost two decades, bacterial isolates have been collected from patients and sent to a national repository. “Our collaborator had special access to this repository,” Earl explained. “That just opened up the box for us to think about what we could do with that amazing collection and how it could be useful to answer long-standing questions in the field about how bacteria adapt during chronic infection.”
Previous work by Gal-Mor’s team showed that 2.2 percent of all NTS cases in Israel over a 17-year long period were long-term infections that lasted for 30 days or more.4 By genome sequencing bacterial isolates of 11 chronically infected patients, they uncovered mutations in virulence regulatory genes, but the researchers could not identify conserved patterns across the different patients.
In the new study, Earl, Gal-Mor, and their colleagues performed whole genome sequencing of bacterial isolates from 256 Israeli patients with chronic salmonellosis. To identify mutations that allowed NTS to persist, the team examined isolates from the same patient, comparing the first sample taken at the diagnosis (early) with a subsequent isolate collected at least 30 days after the first (late).
They identified 49 serovars that can cause persistent salmonellosis. A closer look at the late isolates revealed that barA and sirA mutations were the most frequent. “When we found these hits on barA/sirA, we thought that that was a really interesting pathway to be affected during persistence,” said Alexandra Grote, a postdoctoral researcher in Earl’s group and coauthor of the paper.
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