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Elucidating the role of biofilms in ETEC pathogenesis

Award Number: R56AI189922
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: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Elucidating the role of biofilms in ETEC pathogenesis - Project Summary. Enterotoxigenic Escherichia coli (ETEC) are one of the most severe diarrhea-causing pathogens in the world. ETEC infections not only cause mortality among children in low- to middle-income countries, but they can also lead to co-morbidities like malnutrition and growth stunting. ETEC vaccine development has been a global health priority for over 50 years, but no licensed ETEC vaccines currently exist. ETEC vaccine antigens have been largely based on 1) enterotoxins that cause fluid secretion and 2) colonization factors (CFs) that allow ETEC to adhere to the small intestines. However, immunity to heat-labile enterotoxin (LT) does not protect against heat-stable enterotoxin (ST)-producing ETEC, and almost 30 antigenically different CFs have been identified. ETEC heterogeneity may be one of the main reasons we lack a universally protective vaccine, so conserved non-canonical adhesins are receiving increased interest as vaccine antigens. However, there have been no attempts to identify novel antigens from ETEC biofilms. Biofilms are sticky heterogenous matrices that most bacteria use to survive, and our new data demonstrate that immunization with heat-killed biofilm-grown ETEC protects in a dam/pup model. Previous studies have demonstrated that ETEC form biofilms at environmental temperatures, but we have recently identified the growth conditions that allow ETEC to produce biofilms at body temperature. Here we demonstrate that ETEC produce robust biofilms when cultured in chemically defined media containing lactate and high levels of magnesium. Lactate and magnesium are sensed by the LldR and PhoP transcriptional regulators, respectively, but how their regulons synergize to promote ETEC biofilm formation is not known. The enterotoxins are well-known to transiently increase luminal chloride concentrations in the intestinal lumen, and we recently demonstrated that ST simultaneously causes magnesium limitation. Therefore, it is important to understand if enterotoxin activity controls ETEC’s access to host metabolites, ions, or proteins that regulate biofilm formation and virulence. This research is significant because we will identify molecular mechanisms that regulate ETEC biofilm formation and identify novel biofilm antigens that may be needed to induce protective immunity. Our specific aims will test the central hypothesis that ETEC establish residence as biofilms (so induction of anti-biofilm immunity is important) and express enterotoxins to alter the availability of luminal metabolites to outcompete closely related species. Our specific aims are to test the hypotheses that 1) overlapping transcriptional networks respond to lactate and magnesium to promote ETEC biofilm formation, 2) enterotoxins regulate access to lactate and magnesium, and 3) immunization with ETEC biofilms protects against heterologous ETEC challenge.


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 = $382,500 )
2026	2026	THE ADMINISTRATORS OF TULANE EDUCATIONAL FUND	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Allergy and Infectious Diseases Research	000	1	8/18/2026	NEW	$382,500
														Subtotal = $382,500

Grand Total All Awards = $382,500

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Elucidating the role of biofilms in ETEC pathogenesis

Award Number: R56AI189922

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: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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