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Stephane Benoit

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Senior Research Scientist

I was born and raised near Lyon, France. My research interests have been mostly centered on the role of metals in bacterial physiology and virulence. My PhD research, in the lab of Dr Marie-Andrée Mandrand-Berthelot (in Lyon) focused on E. coli formate dehydrogenases and hydrogenases, enzymes that contain metals such as selenium, molybdenum, iron and nickel. 

After obtaining my PhD in 1999, I moved to the United States and started to work on spirochetes at the University of Georgia (UGA) with Dr. Frank Gherardini (now at NIH RML in Hamilton, MT). My research projects included the metal utilization and metal-dependent gene regulation in Treponema pallidum (syphilis) and Borrelia burgdorferi (Lyme disease), with a special emphasis on manganese.

In 2001, I joined the lab of Dr. Robert Maier at UGA and worked on two nickel-containing enzymes, hydrogenase and urease, in various microorganisms (Helicobacter pylori, Helicobacter hepaticus and Salmonella enterica Typhimurium). My current research interests have expanded since, and now include: 

  • Antimicrobial nickel chelation therapy in Enterobacteriaceae (Salmonella enterica Typhimurium, Infantis, and Reading; Klebsiella pneumoniae) and campylobacters (C. jejuni, C. concisus).
  • Hydrogenases and respiratory pathways in helicobacters (H. pylori, H. hepaticus) and campylobacters (C. concisus, C. fetus, C. hyointestinalis, C. jejuni)
  • Oxidative stress resistance through methionine sulfoxide recycling (H. pylori)
  • Iron-sulfur clusters maturation (H. pylori)
  • CORM, a new class of antimicrobials-collaboration with Binghe Wang (GSU).
  • Antimicrobial effect of metal compounds-collaboration with Yiping Zhao (UGA)
  • Stepping outside microbiology: using metal chelation to inhibit Alzheimer’s ß-amyloid aggregation.
Education:

BTS La Martiniere Duchere, Lyon, France

Licence Universite de Franche-Comte, Besancon, France

Maitrise Universite Claude Bernard-Lyon I, Lyon , France

DEA Universite Claude Bernard-Lyon I and Institut National des Sciences Appliquees (INSA), Lyon, France.

Ph.D. Biochemistry (Microbiology), INSA Lyon, France (Mandrand-Berthelot lab), 1999.  Thesis: the aerobic formate dehydrogenase of Escherichia coli:  physiological role, topological study and transcriptional analysis of the fdoGHI operon.

 

Research Interests:

- the role of metals (especially nickel, Ni) and hydrogen (H2) in pathogenic bacteria, such as Helicobacter pylori, Salmonella Typhimurium and Klebsiella pneumoniae. We are interested in all aspects of Ni homeostasis, including Ni transport , Ni storage, Ni-dependent gene regulation and Ni-maturation of enzymes such as urease and hydrogenase; the latter are complex processes that require a battery of accessory proteins.      

- metal chelation and metal compounds as novel approaches to combat multi-drug resistant bacteria, including MDR Salmonella and MDR (NDM-1 positive) Klebsiella.

- the maturation and role of iron-sulfur clusters in H. pylori, which relies exclusively on the Nif system to synthesize and distribute its Fe-S clusters; this is highly unusual since the Nif system is dedicated to the Fe-S maturation of nitrogenase, an enzyme that is not present in H. pylori

- the characterization of respiratory pathways and virulence factors in the emerging pathogen Campylobacter concisus, a bacterium strongly associated with oral and inflammatory bowel diseases. Our lab recently reported the construction of C. concisus mutants for the first time. We were able to successfully inactivate genes encoding for a H2-evolving hydrogenase and a tetrathionate reductase. 

- the role of protein-bound methionines in combating oxidative stress:  catalase enzymes are mostly known for their function as H2O2 dissipating enzymes but our lab showed that the H. pylori enzyme can quench HOCl through its (Methionine Sulfoxide Reductase, Msr)-repairable Met residues, regardless of whether the enzyme is catalytically active or not, therefore protecting the cell. A similar role (oxidative stress resistance through Msr-recycled Met) has also been recently shown for H. pylori urease. 

Labs (via personnel):
Labs:
Selected Publications:

Benoit SL, Maier RJ. Copper toxicity towards Campylobacter jejuni is enhanced by the nickel chelator dimethylglyoxime. Metallomics, Dec 28, 2021

Benoit SL, Maier RJ, Sawers, GR, Greening C. Molecular hydrogen metabolism : a widespread trait of pathogenic bacteria and protists. MMBR, Jan 29, 2020.

Benoit SL, Schmalstig, AA, Glushka, J., Maier, SE. Edison, AS, Maier, RJ. Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens. Sci.  Reps., Sept. 21, 2019.

Maier RJ, Benoit SL. Role of nickel in microbial pathogenesis. Inorganics 7(7). June 26, 2019.

Benoit SL, Maier RJ. Site-directed mutagenesis of Campylobacter concisus respiratory genes provides insight into the pathogen's growth requirements. Sci. Reps., Sept. 21, 2018.

Courses Regularly Taught:

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