# Host Cell Signaling Pathways Induced by Salmonella

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $535,012

## Abstract

PROJECT SUMMARY
Salmonellosis continues to be a major Public Health challenge. Salmonella enterica encompasses multiple
serovars that are associated with distinct pathogenic features and host specificities. S. enterica serovar Typhi
for example, is the cause of typhoid fever, a systemic disease of humans that leads to an estimated 200,000
deaths worldwide. In contrast, the broad host S. Typhimurium causes limited gastroenteritis and is one of the
most common causes of food-borne illnesses in the industrialized world. The pathogenicity of all S. enterica
serovars requires the activity of two type III protein secretion systems (T3SS) encoded within their
pathogenicity islands 1 and 2. These T3SSs direct the translocation of a battery of bacterial effectors with the
capacity to modulate a variety of cellular functions. Working in conjunction with one another, these effectors
modulate actin cytoskeleton dynamics, host-cell gene expression, vesicle trafficking, and innate and acquired
immune responses, thus allowing Salmonella to gain access to and replicate within host cells, avoid host
defenses, induce intestinal inflammation, and reach deeper tissues. Despite the significant progress, however,
much remains to be learned as the biochemical activities and/or relevant cellular targets of many Salmonella
effectors remain uncharacterized. The objectives of this proposed research is to study the functional interface
between Salmonella and its host shaped by the activities of T3SS effectors. More specifically, we intend to
define the mechanisms by which the Salmonella T3SS effectors modulate signaling pathways leading to
intestinal inflammation, a critical step in its pathogenesis. In addition, we will study the mechanism by which a
recently discovered cell intrinsic host defense pathway restricts Salmonella intracellular replication. These
studies will advance the understanding of the cell biology of Salmonella enterica infections and potentially
facilitate the development of novel therapeutic and prevention strategies. Furthermore, these studies may
establish new paradigms of host-pathogen interactions that may be applicable to other important pathogens
that have evolved close associations with their respective hosts.

## Key facts

- **NIH application ID:** 10134995
- **Project number:** 5R01AI055472-28
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Jorge E Galan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $535,012
- **Award type:** 5
- **Project period:** 1995-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134995

## Citation

> US National Institutes of Health, RePORTER application 10134995, Host Cell Signaling Pathways Induced by Salmonella (5R01AI055472-28). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10134995. Licensed CC0.

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