Michael Stephen Trent
University of Georgia, GA·Microbiology & Immunology
Gram-negative bacteria such as Escherichia coli are wrapped in two membranes. The outer membrane is lopsided.
- Fields
Microbiology & Immunology
Biochemistry
- Topics
Gram-negative bacteria
outer membrane
cell envelope
- Grants
- 4 known grants, through Jan 2030
What they work on
- Develop an analytical tool that measures LPS molecules in transit, and combine it with mass spectrometry of the enzyme LpxC and LPS precursors to determine how the YejM-YciM system controls LPS production in E. coli.
- Test whether triggers known to change LPS synthesis, such as added fatty acids and envelope stress, act through YejM-YciM sensing of LPS in the periplasm, the space between the two bacterial membranes.
- Define how the minor lipid cardiolipin boosts MsbA, the essential transporter that flips LPS across the inner membrane, by mapping specific MsbA-cardiolipin contacts and their effect on transport activity.
- Determine whether the cardiolipin-making enzyme ClsA sits next to MsbA in the cell envelope, and how defects in LPS transport feed back to slow LPS synthesis.
- Characterize YhdP, TamB and YdbH, three AsmA-like proteins that span the periplasm, as the main transporters that move glycerophospholipids from the inner to the outer membrane of E. coli.
- Identify helper proteins needed to move glycerophospholipids across the membrane, and measure how losing these transport systems affects outer membrane lipid balance and antibiotic resistance.
- Study surface lipoproteins that Acinetobacter baumannii makes under envelope stress and when it lacks LPS, including how these proteins are moved across the outer membrane.
- Characterize two glycosyltransferases, sugar-attaching enzymes, that work in tandem to transfer sugars during LPS synthesis in A. baumannii.
- Characterize a newly found outer-membrane cardiolipin synthase in A. baumannii and determine how it affects outer membrane integrity.
More about the research
Its inner layer is made of glycerophospholipids (GPLs), the ordinary fats of cell membranes. Its outer layer is made of lipopolysaccharide (LPS), a large lipid coated with sugars. This arrangement forms a tight barrier that keeps out many antibiotics, which is why Gram-negative infections are so hard to treat. No antibiotic in clinical use directly targets how this membrane is built. The lab's grants ask how bacteria make LPS and GPLs, move them to the right place, and keep their amounts in balance. The work uses E. coli as a model and also studies the drug-resistant pathogen Acinetobacter baumannii.
Why it matters
Infections caused by Gram-negative bacteria such as E. coli and the extensively drug-resistant Acinetobacter baumannii are hard to treat because their outer membrane blocks many antibiotics. Identifying the proteins that build and balance this barrier could reveal new targets for drugs against multidrug-resistant infections. The lab's quantitative models could also help predict how antibiotics weaken the bacterial envelope.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
The Cell Envelope of the Multi-Drug Resistant Pathogen Acinetobacter baumannii
NIH · Feb 2020 – Jan 2030
The role of cardiolipin in the biogenesis of the Gram-negative bacterial cell envelope
NIH · Jun 2023 – May 2028
Synthesis and transport of outer membrane components across the Gram-negative cell envelope
NIH · Jan 2023 – Dec 2027
Closest labs
Jochen Zimmer
University of Virginia, VA·Biochemistry
Determine how cellulose biosynthesis is controlled in enterobacteria such as E. coli, building on the lab's structures of the supramolecular cellulose synthase complex that both polymerizes and secretes this glucose chain.
David Cafiso
University of Virginia, VA·Biophysics
Test models of how TonB-dependent transporters such as BtuB, the vitamin B12 transporter, move nutrients across the E. coli outer membrane, using site-directed spin labeling and EPR spectroscopy on active proteins.
Sergei Vakulenko
University of Notre Dame, IN·Microbiology & Immunology
Measure the activity of novel carbapenems against A. baumannii strains producing major CHDLs (enzymes that destroy carbapenems) and other carbapenemases, and use enzyme kinetics and structural studies to explain how the compounds inhibit these enzymes.
The school
University of Georgia: 27 labs on PI Pages, $628M a year on research, 598 research doctorates a year.
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