Role of yersiniabactin precursor escherichelin in promoting enterobacteriaceae colonization and pathogenicity of the inflamed colon
Active Project Grant Awarded Last action
- Award ID
- F31AI197841
- Recipient
-
University Of California, San Diego UEI UYTTZT6G9DT1
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $86,978
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 0% complete
- Originally
- Place of performance
- La Jolla, CA 92093, USA
Award details come from USAspending.gov.
Description
- Abstract
- With the rapid rise of antibiotic-resistant pathogens, there is an increasing need for alternative methods of treating bacterial infections. Probiotics are a potential rising solution as commensals can establish a niche within the host, directly kill pathogens, and starve competitors of key metal ions. One such commensal is escherichia coli (E. Coli). E. Coli nissle 1917 (ECN) is a probiotic E. Coli discovered in the feces of a WW1 soldier who did not get dysentery. One mechanism ECN uses to control its niche is having a wide array of molecules for metal chelation which predominantly sequester iron. Of these chelators, yersiniabactin (YBT) is arguably the most important for ECN because IT is not commonly shared with other enterobacteriaceae and IT is capable of binding not just iron, but zinc, copper, and more metals. During the synthesis of YBT, there is secretion of a precursor molecule hydroxyphenyl-thiazolyl-thiazolinyl-carboxylic acid termed escherichelin. Escherichelin is known to bind iron and has recently been found to bind zinc, but IT is unknown whether escherichelin provides a function in metal competition and growth. Salmonella enterica serovar typhimurium (STM) is a pathogen responsible for millions of infections per year. Additionally, adherent-invasive E. Coli (AIEC) is a pathogenic E. Coli pathovar linked to inflammatory bowel disease and produces YBT. The importance of escherichelin in metal competition or pathogenicity is unknown. To address this knowledge GAP, various knockouts will be created. During the YBT synthesis, there are two required genes, IRP1 and IRP2. Knocking out IRP1 would isolate the production of escherichelin from YBT. Creating an IRP2 mutant would knock out both YBT and escherichelin production. My central hypothesis is that escherichelin functions as a zincophore, contributing to ZN acquisition in commensal and pathogenic E. Coli. In the case of ECN, we hypothesize that escherichelin production will provide a competitive advantage against STM during colitis. In the case of AIEC, we hypothesize that escherichelin will enhance colonization of this pathobiont, potentially exacerbating colitis. To answer this hypothesis my first aim is to use extracted escherichelin and the IRP1 and IRP2 mutants to elucidate whether escherichelin functions as a zincophore in vitro and in vivo. The growth advantage of escherichelin will be assessed in vivo by using a murine model of colitis. Next, growth curves will be performed in different media to measure the growth response when zinc is present. Additionally, a second aim will determine whether zinc acquisition via escherichelin enables ECN to compete with STM in the inflamed GUT and in vitro. To answer this, mice will be CO-infected with the ECN IRP1 mutant and STM. Additionally, we will investigate whether escherichelin boosts pathogenesis, AIEC infections with IRP mutants will be performed. The outcome of this research would inform on metal competition in the GUT during infection and inflammation. This research is necessary to understand potential microbe-based treatments and prophylaxis.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $43,489 | |
| Amendment | $0 | |
| Original award | $43,489 |
Quick answers
Who received award F31AI197841?
F31AI197841 was awarded to University Of California, San Diego by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on November 27, 2026.
How much is award F31AI197841 worth?
$86,978 has been obligated on F31AI197841.
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