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In order to survive within a host organism, pathogenic bacteria have evolved flexible metabolic pathways and defense mechanisms. Dr. Frawley uses the model pathogen Salmonella Typhimurium to study how bacteria respond to host-generated chemical defenses such as nitric oxide. Many key enzymes and pathways are directly inhibited by nitric oxide so, in order to survive, bacteria must find ways to adapt to and repair any damage that occurs. Dr. Frawley is particularly interested in how nitric oxide affects metal-containing proteins and how metal transport impacts bacterial stress resistance. Current work focuses on characterizing the transport proteins that allow Salmonella to alter the concentrations of various metal ions in the cell following nitric oxide exposure and identifying the protective role(s) that manganese plays in helping Salmonella resist this stress.

The Frawley lab is also engaged in collaborative work with the Peterson and Bea labs at ¾ÅÉ« to characterize novel antimicrobial compounds.  As bacteria become increasingly resistant to existing antibiotics, developing new antimicrobial molecules with novel mechanisms of action will be essential for successful treatment of infections.

Selected Publications

Ouyang A,* Gasner KM,* Neville SL, McDevitt CA, Frawley ER. 2022. MntP and YiiP contribute to manganese efflux in Salmonella enterica serovar Typhimurium under conditions of manganese overload and nitrosative stress. Microbiology Spectrum. 10(1): e0131621.

Bea R, North LJ, Horiuchi S, Frawley ER, Shen Q. 2021. Antimicrobial activity and toxicity of analogs of wasp venom EMP peptides. Potential influence of oxidized methionine. Antibiotics. 10(10).

Yousuf S,* Karlinsey JE, Neville SL, McDevitt CA, Libby SJ, Fang FC, Frawley ER. 2020. Manganese import protects Salmonella enterica serovar Typhimurium against nitrosative stress. Metallomics. 12(11): 1791-1801.

Roldan RJ,* Pajarillo AO, Greenberg JD, Karlinsey JE, Cafiero M, Frawley ER, Peterson LW. 2020. Propargylglycine-based antimicrobial compounds are targets of TolC-dependent efflux systems in Escherichia coli.  Bioorganic and Medicinal Chemistry Letters. 30(2): 126875.

Frawley ER, Karlinsey JE, Singhal A, Libby SJ, Paschalis-Thomas D, Ischiropoulos H, Fang FC. 2018. Nitric oxide disrupts zinc homeostasis in Salmonella enterica serovar Typhimurium. mBio. 9(4) doi:10.1128/mBio.01040-18

Fang FC, Frawley ER, Tapscott T, Vazquez-Torres A. 2016. Discrimination and Integration of Stress Signals by Pathogenic Bacteria. Cell Host and Microbe. 20(2): 144-53.

Fang FC, Frawley ER, Tapscott T, Vazquez-Torres A. 2016. Bacterial Stress Responses during Host Infection. Cell Host and Microbe. 20(2): 133-43.

Frawley ER and Fang FC. 2014. The ins and outs of bacterial iron metabolism. Molecular Microbiology. 93(4): 609-616.

Frawley ER, Crouch ML, Bingham-Ramos LK, Robbins HF, Wang W, Wright GD, Fang FC. 2013. Iron and Citrate Export by a Major Facilitator Superfamily Pump Regulates Metabolism and Stress Resistance in Salmonella Typhimurium. PNAS. 110(29): 12054-12059.

Karlinsey JE, Bang IS, Becker LA, Frawley ER, Porwollik S, Robbins HF, Thomas VC, Urbano R, McClelland M, Fang FC. 2012. The NsrR Regulon in Nitrosative Stress Resistance of Salmonella enterica serovar Typhimurium. Molecular Microbiology. 85(6): 1179-1193.

Frawley, ER and Kranz, RG. 2009. CcsBA is a cytochrome c synthetase that also functions in heme transport. PNAS. 106(25): 10201-10206.

* denotes undergraduate researchers at ¾ÅÉ«