Mentor: Rimi Chowdhury, Ph.D.

Shigella flexneri is a human-adapted enteric pathogen that causes shigellosis, a severe form of infectious diarrhea. Upon ingestion, S. flexneri navigates to the colon and invades epithelial cells, triggering a strong inflammatory response by the immune system. Reactive oxygen species (ROS) are a major component of this inflammatory response, aimed at killing the invading pathogen. However, the mechanisms by which S. flexneri manages to survive in this hostile environment are poorly understood. Cysteine, an essential amino acid having a free sulfhydryl group, can neutralize ROS. Therefore, we hypothesized that the cysteine biosynthesis pathway may play a crucial role in neutralizing free radicals and ROS. To test this, we first identified the essential gene cysM involved in the cysteine biosynthetic pathway, followed by constructing deletion mutants by replacing cysM with kan and testing their growth rate relative to wildtype S. flexneri in presence of ROS. We found that the wildtype S. flexneri could survive in moderate amounts of ROS stress, but the mutant strain failed to grow at all. This confirmed our hypothesis that the cysteine biosynthesis gene cysM is essential for S. flexneri’s survival under oxidative stress. This study advances the field of host-pathogen interactions by uncovering how S. flexneri withstands oxidative stress during its infection cycle in the human host.

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