Androgens modulate staphylococcus aureus signaling and pathogenesis
Active Project Grant Awarded Last action
- Award ID
- R01AI187273
- Recipient
-
The University Of Texas Southwestern Medical Center UEI YZJ6DKPM4W63
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,268,906
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 38% complete
- Place of performance
- Dallas, TX 75390, USA
Award details come from USAspending.gov.
Description
- Abstract
- Staphylococcus aureus soft tissue and skin infections affect seven-to-ten percent of hospitalized patients and skin infections are the third most common reason for presentation to the emergency room. Most infections of the skin are caused by s. Aureus, with men having higher rates of infection with s. Aureus compared to women. Adding to the burden of disease posed by these pathogens has been the development of antibiotic-resistant strains of bacteria such as methicillin-resistant s. Aureus (mrsa). Despite the clear pathogenic potential of s. Aureus species, IT asymptomatically colonizes the nasal passages of one-third of people. This duplicity is due to coordinated regulatory networks that alter virulence factor expression depending on the sensed environmental conditions. The most well-described of these is the accessory gene regulator (AGR) quorum-sensing system. In this proposal we outline our recent findings that men secrete greater amounts of testosterone at the skin surface compared to women, and our preliminary data indicating that testosterone amplifies s. Aureus virulence. Our hypothesis is that skin secreted testosterone promotes s. Aureus virulence through activation of quorum-sensing mechanisms. To address this question, in aim 1 we will investigate the mechanism of testosterone stimulation of s. Aureus AGR signaling. We will use genetic and biochemical approaches to determine how testosterone activates the AGR regulon, and we will investigate the agrc histidine kinase as the primary testosterone target. In aim 2 we will determine the impact of testosterone on s. Aureus skin infection in vivo using mouse models. We will test this phenotype using skin infection models paired with bioluminescent strains of s. Aureus with and without mutations in AGR components. We will also investigate genetically engineered mice with reduced androgen production in the skin. In aim 3 we will identify the s. Aureus enzymes that metabolize skin androgens over time and their impact on quorum sensing. Our preliminary findings indicate that this pathogen breaks down testosterone into androstenedione. Using bioinformatic approaches, we have identified potential androgen- degrading enzymes encoded in the s. Aureus genome and we will characterize these targets using bacterial genetic and biochemical approaches. The work proposed in this application will determine how testosterone regulates s. Aureus pathogenesis at the skin surface and identify novel therapeutic targets for the treatment of s. Aureus.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $625,292 | |
| Original award | $643,614 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| The Regents Of The University Of Colorado | $455,712 |
Quick answers
Who received award R01AI187273?
R01AI187273 was awarded to The University Of Texas Southwestern Medical Center by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on December 6, 2024.
How much is award R01AI187273 worth?
$1,268,906 has been obligated on R01AI187273.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award