# Host Cell Signaling Pathways Induced by Salmonella

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $605,948

## Abstract

PROJECT SUMMARY
Salmonellosis continues to be a major Public Health challenge resulting in more than 300,000 death world-
wide. In the US alone, Salmonella causes an estimated 1 million infections resulting in annual economic
burden of $2.8 billion. Salmonella enterica encompasses multiple serovars that are associated with distinct
pathogenic features and host specificities. Some serovars (e. g. S. Typhimurium) exhibit broad host specificity,
cause self-limiting gastroenteritis, and are one of the most common causes of food-borne illnesses in the
industrialized world. In contrast, other serovars such as S. Typhi exhibit remarkable host specificity limiting
their ecology to the human host where it causes typhoid fever, a systemic disease that leads to an estimated
200,000 deaths worldwide. 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 objective of this
proposed research is to study host/Salmonella interactions that are shaped by the coordinated activities of its
T3SS effectors. We will focus our efforts on the study of mechanisms by which an intrinsic host defense
pathway controls Salmonella replication within cells, and how the bacteria counter this defense mechanism
with its effector proteins. In addition, we will examine how some of this effector proteins trigger intestinal
inflammation, which is critical for Salmonella pathogenesis. 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:** 10765702
- **Project number:** 5R01AI055472-31
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Jorge E Galan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $605,948
- **Award type:** 5
- **Project period:** 1995-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765702

## Citation

> US National Institutes of Health, RePORTER application 10765702, Host Cell Signaling Pathways Induced by Salmonella (5R01AI055472-31). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10765702. Licensed CC0.

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