Michael Federle
University of Illinois Chicago, IL·Microbiology & Immunology
Bacteria can talk to one another. Using chemical signals, they sense how many of their neighbors are present and switch genes on together, a behavior called quorum sensing.
- Fields
Microbiology & Immunology
Biochemistry
Medicine & Clinical Research
- Topics
Streptococcus pyogenes
Group A Streptococcus
quorum sensing
- Grants
- 2 known grants, through Jun 2031
What they work on
- Identify the factor made by the quorum-regulated biosynthetic gene cluster of Streptococcus pyogenes, along with its biosynthetic intermediates, that suppresses inflammatory responses in macrophages.
- Determine the macrophage target and mechanism by which quorum-ON bacteria inhibit NF-kB activity and cytokine production such as TNF and IL-6, despite comparable bacterial adherence and cell viability.
- Measure the physiological consequences of quorum-driven immunosuppression and the advantage it gives the bacteria, using animal infection models and human explant tissue, including treatment with a specific quorum-sensing inhibitor.
- Define the nuclear defects behind suppressed inflammation in infected macrophages, examining phosphorylation and DNA binding of nuclear factors c-Rel and Sam68 with phosphoproteomics and CUT&RUN genome-binding assays.
- Identify the host receptors and signaling pathways, particularly cAMP signaling through adenylate cyclase Adcy4 and lectin-like receptors, that relay the signal from the ribitol-N-acetylglucosamine-modified bacterial cell wall to the nucleus.
- Reconcile immunosuppression in culture with worse disease in animals by testing competing models: delayed then excessive immune activation versus suppression of interferon-mediated protection.
More about the research
Streptococcus pyogenes, also known as Group A Streptococcus, is a common human pathogen that causes strep throat and skin infections and, in severe cases, invasive, life-threatening disease. Work in this lab concerns how quorum sensing changes the bacterium's surface and, in turn, blunts the first line of host defense. Two linked projects examine this from the bacterial side, identifying the molecule responsible, and from the host side, tracing how the signal reaches and disables inflammatory gene expression inside immune cells. Because there is no licensed vaccine, antibiotic resistance is rising, and severe infections are increasing, understanding this immune evasion is pressing.
Why it matters
Group A Streptococcus causes disease ranging from sore throats to invasive infections, there is no licensed vaccine, and antibiotic resistance is growing. By pinpointing the bacterial factor and the host proteins it manipulates, this work could reveal drug targets, including quorum-sensing inhibitors, that restore normal immune signaling and help the body clear the infection before it spreads and causes damage.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Debra Bessen
New York Medical College, NY·Microbiology & Immunology
Screen serum collected from children just before a new group A streptococcal infection to identify leading vaccine candidate antigens for which they lack protective antibodies.
Jenifer Coburn
Medical College of Wisconsin, WI·Microbiology & Immunology
Test whether the interaction between the Borrelia burgdorferi surface protein P66 and the macrophage receptor SIRPα weakens innate and adaptive immunity, comparing p66-deficient and gene-restored bacteria in mice over six infection time points.
Shelley Payne
University of Texas at Austin, TX·Microbiology & Immunology
Determine how carbon-source availability tells Shigella flexneri where it is in the host, by testing mutants defective in specific carbon metabolism pathways for invasion, intracellular replication, and cell-to-cell spread in human cells.
The school
University of Illinois Chicago: 42 labs on PI Pages, $532M a year on research, 359 research doctorates a year.
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