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Understanding how flagellar accessory proteins provide enhanced abilities to bacterial motility responses and fitness in the gastric pathogen Helicobacter pylori

Award Number: R01AI198564
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/05/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

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Understanding how flagellar accessory proteins provide enhanced abilities to bacterial motility responses and fitness in the gastric pathogen Helicobacter pylori - Our proposed research focuses on defining the mechanism of action of flagellar accessory proteins and how they enhance bacterial fitness and colonization using the ulcer-causing bacterium Helicobacter pylori. Many bacteria decorate their flagella with additional proteins but it is mostly unknown how they augment flagellar function. We recently determined the identity of several of these accessories in H. pylori and found that they do not—as predicted—enhance motility but instead regulate it and are absolutely required for stomach infection. Surprisingly, these proteins were homologs of type 4 pili proteins called PilMNO but have evolved to work with the flagella. There remains a gap, however in our understanding of how these accessory proteins operate and benefit H. pylori. Continued existence of this gap prevents us from gaining a full understanding of H. pylori’s pathogenic mechanisms and, in the long term, creating new drugs to thwart these processes. Millions of peo- ple in the U.S. and worldwide are infected by H. pylori and suffer from its associated diseases—ulcers and gastric cancer, which impact millions of people annually. H. pylori is here to stay based on recent studies that show H. pylori incidence has stabilized in the developed world. Furthermore, current therapies to cure H. pylori infection fail with unacceptable frequency, e.g., recent estimates in the United States have found that 20-25% of infected individuals are not cured by the current therapeutic regime in part due to rising antibiotic resistance. New drug targets are desperately needed. The overall objective of this application is to provide insights into how flagellar accessory proteins confer new abilities on motility, cell responses, and infection. Our central hy- pothesis is that flagellar PilMNO act as a signaling hub that respond to signals that arise at the flagellar fila- ment and control a cellular response that includes aggregate formation and motility cessation. Our hypothesis has been formulated from robust multi-disciplinary preliminary data that includes multiple motility assays, mo- lecular microbiology, genetic screens, biochemistry, animal colonization studies, mathematical modeling, and high resolution microscopy. Our approach has three Aims, which use the same range of approaches. In Aim 1, we define the nature of flagella-based input signals sensed by flagellar PilMNO. In Aim 2 we determine the cell signaling pathway activated by flagellar PilMNO. In Aim 3, we identify how flagellar PilMNO stop flagellar motil- ity. The proposed research is innovative in its multidisciplinary nature, that it will create new knowledge about the functions of flagellar accessory proteins in general and specifically in H. pylori, and that it will pioneer new approaches to study flagellar function. The proposed research is significant because it will advance our under- standing of flagellar accessories and how H. pylori has improved its fitness using them.The long-term out- comes generated by this research are likely to provide insights that will enable creation of new drugs against H. pylori and other microbes that use flagella to cause disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $599,642 )
2026	2026	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Allergy and Infectious Diseases Research	000	1	5/5/2026	NEW	$599,642
														Subtotal = $599,642

Grand Total All Awards = $599,642

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Understanding how flagellar accessory proteins provide enhanced abilities to bacterial motility responses and fitness in the gastric pathogen Helicobacter pylori

Award Number: R01AI198564

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/05/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

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