Jeff Boyd
Research Interests
Detection and response of organisms to oxidative stress, biological iron-sulfur cluster assembly and repair
We are currently working on two interrelated projects in our lab. The first project examines the physiological response of a pathogenic bacterium to oxidative stress. The second project uses a model organism to dissect how organisms metabolize small oxidant sensitive inorganic cofactors.
1) Staphylococcus aureus is a human commensal bacterium that is naturally carried by 20-50% of the population. This bacterium can cause infections that range from relatively harmless furuncles and carbuncles to life threatening endocarditus and necrotizing pneumonia. Staphylococcus aureus infections have historically been associated with open-wounds, hospital visits, and immuno-compromised persons, but recently, infections are being seen in relatively healthy individuals that have not been associated with hospital settings (community acquired infections). Many of these infections are caused by strains of S. aureus that are resistant to nearly all commonly used antibiotics, including methicillin, greatly complicating the treatment of infections caused by this aggressive pathogen.
One research focus of our laboratory is to determine how community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) detects and responds to host defense systems. Neutrophil granulocytes are white blood cells that provide humans with a “first line” of defense against CA-MRSA infections. Neutrophils engulf and kill bacteria, in part, by bombarding them with poisonous oxidants such as bleach, superoxide, and hydrogen peroxide. Remarkably, strains of CA-MRSA can survive this attach and successfully invade host tissues. Our lab uses a variety of biochemical and genetic techniques to understand what is unique about the physiology of CA-MRSA that allows it withstand high degrees of oxidative stress. We also study how CA-MRSA detects and responds to the presence of neutrophils and oxidative stress.
2) The second focus of our work examines the metabolism of simple inorganic cofactors called iron-sulfur (Fe-S) clusters. Proteins with [Fe-S] clusters have an ever-expanding repertoire of biological functions. These metalloproteins are involved in some of the most fundamental life-sustaining processes on Earth such as biological nitrogen fixation, photosynthesis, and cellular respiration. To this end, the evolution of all life can be considered dependent on the successful and controlled synthesis and maintenance of [Fe-S] clusters. Free iron and free sulfur are toxic to cells and Iron-sulfur clusters are easily damaged by oxidants. Therefore, complex cellular machinery has evolved to tightly control the synthesis and repair of [Fe-S] clusters. Despite the recognized and central role of [Fe-S] clusters in biology, our understanding of how these inorganic cofactors are metabolized is limited by our lack of basic knowledge in which gene products control the synthesis, trafficking, and repair of these clusters and how these gene products are integrated into cellular metabolic networks.
The work on our second project aims to address remaining questions in [Fe-S] cluster metabolism and take advantage of integrative studies to uncover the biochemical function of genes of unknown function involved in [Fe-S] metabolism. Because all cells face similar challenges in integrating their metabolism and many metabolic paradigms are conserved, these studies are conducted using the model bacterium Salmonella enterica for simplicity and technical feasibility.
Selected Publications
Chen Y.T., Liu Z., Fucich D., Giulieri S.G., Liu Z., Wadhwa R., Rios G., Henschel H., Tyagi N., Olivier F.A.B., Monk I.R., Shaw S.S., Sridhar S.H., Drikic M., Bianco C., Lohia G., Beg A.Z., Planet P., Lewis I.A., Sebra R., Traven A., Hachani A., Stinear T.P., Howden B.P., Boyd J.M., Riquelme S.A., Wang C., Prince A., and Wong Fok Lung T., Regulation of airway fumarate promotes S. aureus pneumonia. Nature Communications. Accepted.
Boyd J.M., Price E.E., Roman Rodriguez F., Burchat N., Norambuena J., DuMont A.L., Torres V.J., Sampath H., Treatment of Staphylococcus aureus with environmentally relevant concentrations of triclosan activates SaeRS-dependent virulence factor expression. 6/2025 Antimicrobial Agents and Chemotherapy. PMID: 40531055
Sabo E., Nelson C., Tyagi N., Stark V., Aasman K., Morrison C., Boyd, J.M.*, Holz R.C.*, Practical Spectrophotometric Assay for the Cysteine Desulfurase SufS from Staphylococcus aureus, a Potential Antibiotic Target. 1/2025 Antibiotics. PMID: 40001373
* co-corresponding authors
pmc.ncbi.nlm.nih.gov/articles/PMC11851464
Stevens M., Doud E.H., Norambuena, J., Tepper K., Trindl C.A., Lander G.C., Carpenter R., Chapman E., Boyd J.M., Wells C., Chen Q., Johnson S.M., Deciphering the unique mechanism whereby bis-sulfonamido-2-phenylbenzoxazole (PBZ) GroEL/ES inhibitors modulate chaperonin ATPase and client protein folding functions. ChemRxiv.
chemrxiv.org/engage/chemrxiv/article-details/677d8956fa469535b91e263e
Rios-Delgado G., McReynolds A.K.G., Pagella E.A., Norambuena J., Briaud P., Zheng V., Munneke M.J., Kim J., Racine H., Carroll R., Zelzion E., Skaar E., Bose J.L., Parker D., Lalaouna D., Boyd J.M. The Staphylococcus aureus non-coding RNA IsrR regulates TCA cycle activity and virulence. 11/2024 Nucleic Acids Research. PMID: 39704109
pmc.ncbi.nlm.nih.gov/articles/PMC11879123
Pederick J.L. Vandborg B.C., George A., Bovermann H., Boyd J.M., Freundlich J.S., Bruning J.B. Identification of cysteine metabolism regulator (CymR)-derived pentapeptides as nanomolar inhibitors of Staphylococcus aureus O-acetyl-ʟ-serine sulfhydrylase (CysK). 11/2024 ACS Infectious Disease. PMID: 39705018
pmc.ncbi.nlm.nih.gov/articles/PMC11429995
Boyd J.M., Esquilín-Lebrón K., Campbell C.J., Ryan Kaler K., Norambuena J., Foley M.E., Stephens T.G., Rios G., Mereddy G., Zheng V., Bovermann H., Kim J., Kulczyk A.W., Yang J.H., Greco T.M., Cristea I.M., Carabetta V.J., Beavers W.N., Bhattacharya D., Skaar E.P., Parker D., Carroll R.K., Stemmler T.L., Fpa (YlaN) is an iron(II) binding protein that functions to alleviate Fur-mediated repression of gene expression in Staphylococcus aureus. 10/2024 mBio. PMID: 39440976
pmc.ncbi.nlm.nih.gov/articles/PMC11559061
Sant D., Mateen A.I., Sullivan R., Boyd J.M., Carabetta V.J., Yadavalli S.S., Sun J.S., Emerging Themes in Microbial Stress Response and Mechanistic Insights: Key Findings from the Fall 2024 ASM Theobald Smith Society Meeting, 1/2025 mSphere.
journals.asm.org/doi/10.1128/msphere.01008-24
Muneeswaran Z.P., Teoman B., Wang Y., Chaudhry H., Brinzari T.V., Verma G., Ranasinghe L., Ryan Kaler K.M., Huang K., He, X., Thomas B.L., Xu S., Cheng C.Y., Boyd J.M., Chen D., Hao Z., Ma S., Asefa T., Pan L., Dubovoy V., Novel anionic surfactant-modified chlorhexidine and its potent antimicrobial properties. 12/2023 Dalton Transactions. PMID: 38224288.
pubmed.ncbi.nlm.nih.gov/38224288
Leanse L.G., dos Anjos C., Ryan Kaler K., Hui J., Boyd J.M., Hooper D.C., Anderson R.R., Dai T., Blue light potentiates antibiotic activity in bacteria via parallel pathways of hydroxyl radical production and enhanced antibiotic uptake. 8/2023 Advanced Science. PMID: 37946633
pmc.ncbi.nlm.nih.gov/articles/PMC10754126
Hossain S., Morey J.R., Neville S.L., Ganio K., Radin J.N., Norambuena J., Boyd J.M., McDevitt C.A., Kehl-Fie T.E., Host subversion of bacterial metallophore usage drives copper intoxication. 8/2023 mBio. PMID: 37737591
pmc.ncbi.nlm.nih.gov/articles/PMC10653882
Kim G.L., Kim J., Norambuena J., Boyd J.M., Parker D., Impact of the pentose phosphate pathway on metabolism and pathogenesis of Staphylococcus aureus. 6/2023 PLoS Pathogens. PMID: 37440594
journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011531
Norambuena J., Al-Tameemi H., Bovermann H., Kim J., Beavers W.N., Skaar E.P., Parker D., Boyd J.M. Copper ions inhibit pentose phosphate pathway function in Staphylococcus aureus. 5/2023 PLoS Pathogens. PMID: 37235600
journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011393
Ramírez-Hernández M., Norambuena J., Hu H., Thomas B., Tang C., Boyd J.M.*, Asefa T.* Repurposing Anthelmintics: Effects of Rafoxanide and Copper-Functionalized SBA-15 Carriers Against Methicillin-Resistant Staphylococcus aureus (MRSA). 3/2023 American Chemical Society Applied Materials & Interfaces. PMID: 36975176
* co-corresponding authors
pmc.ncbi.nlm.nih.gov/articles/PMC10257252
Andrews, T., Ficken K., Fey P.D., Duffy S., Boyd J.M., Novel Transducing Bacteriophage Infecting Staphylococcus epidermidis Contributes to the Expansion of a Novel Siphovirus Genus and Implies Genus is Inappropriate for Phage Therapy. 2/2023 mSphere. PMID: 37017574
pmc.ncbi.nlm.nih.gov/articles/PMC10286716
Hudspeth, J.D., Boncella A.E., Sabo E.T., Andrews T., Boyd J.M., Morrison C.N., Structural and Biochemical Characterization of Staphylococcus aureus Cysteine Desulfurase Complex SufSU. 11/2022 American Chemical Society Omega. PMID: 36506149
pubs.acs.org/doi/10.1021/acsomega.2c05576
Andrews T.P., Hoyer J.S., Fahrenfeld N.L., Boyd J.M.*, Duffy S.* Complete genome sequences of five Phietaviruses infecting Staphylococcus aureus. 10/2022 Microbiology Resource Announcements. PMID: 36173192
* co-corresponding authors
journals.asm.org/doi/10.1128/mra.00855-22
Teoman T., Muneeswaran Z.P., Verma G., Chen D., Brinzari T.V., Almeda-Ahmadi A., Norambuena J., Xu S., Ma S., Boyd J.M., Armenante P.M., Potanin A., Pan L., Asefa T., Dubovoy V., Cetylpyridinium Trichlorostannate: Synthesis, Antimicrobial Activity and Controlled-Release Properties via Electrical Resistance Tomography. 12/2021 American Chemical Society Omega. PMID: 34984275
pmc.ncbi.nlm.nih.gov/articles/PMC8717397
Esquilin-Lebron K., Dubrac, S., Barras F., Boyd J.M. Bacterial approaches for assembling iron-sulfur proteins. 12/2021 mBio. PMID 34781750.
journals.asm.org/doi/10.1128/mbio.02425-21
Price E.E., Rudra P., Norambuena J., Román-Rodríguez F., Boyd J.M., Tools, strains, and strategies to effectively conduct anaerobic and aerobic transcriptional reporter screens and assays in Staphylococcus aureus. 8/2021 Applied and Environmental Microbiology. PMID: 34406831.
pubmed.ncbi.nlm.nih.gov/34406831
Price E.E., Román-Rodríguez F., Boyd J.M., Bacterial approaches to sensing and responding to respiration and respiration metabolites. 8/2021 Molecular Microbiology. PMID: 34387370.
Patel J.S., Norambuena J., Al-Temeemi H., Perryman A.L., Wang X., Occi J., Russo R., Park S., Zimmerman M., Ho H.P., Perlin D.S., Dartois V., Connell N., Ekins S., Kumar P., Boyd J.M.*, Freundlich J.S.* Bayesian Modeling and Intrabacterial Metabolism Applied to Drug-Resistant Staphylococcus aureus. 8/2021 ACS Infectious Diseases. PMID: 34342426.
* co-corresponding authors
pubmed.ncbi.nlm.nih.gov/34387370
Carabetta, V.J., Esquilin-Lebron K., Zelzion E., Boyd J.M., Genetic approaches to uncover gene products involved in iron-sulfur protein maturation: High throughput genomic screening using transposon-sequencing. 2021 Methods in Molecular Biology. PMID: 34292543.
link.springer.com/protocol/10.1007/978-1-0716-1605-5_3
Ferrer-González E., Huh H., Al-Tameemi H.M., Boyd J.M., Lee S.H., and Pilch D.S., Impact of FtsZ Inhibition on the Localization of the Penicillin Binding Proteins in Methicillin-Resistant Staphylococcus aureus. 7/2021 Journal of Bacteriology. PMID: 34031040.
pmc.ncbi.nlm.nih.gov/articles/PMC8297533
Kim G.L., Hooven T., Norambuena-Morales J., Li B. Boyd J.M., Yang J., Parker D. Growth and stress tolerance comprise independent metabolic strategies critical for Staphylococcus aureus infection. 3/2021 mBio. PMID: 34101490.
pmc.ncbi.nlm.nih.gov/articles/PMC8262855
Juttukonda L.J., Beavers W.N., Horning K.J., Unsihuay D., Horvath D.J., Kim K., Weiss A., Pishchany G., Al-Tameemi H., Boyd J.M., Sulikowski G., Bowman E.B., and Skaar E.P. A small molecule modulator of metal homeostasis is toxic toGram-positive pathogens. 10/2020 mBio. PMID: 33109764.
pmc.ncbi.nlm.nih.gov/articles/PMC7593973
Al-Tameemi H., Beavers W.N., Norambuena-Morales J., Skaar E., Boyd J.M. Staphylococcus aureus lacking a functional MntABC manganese import system have increased resistance to copper. 4/2021 Molecular Microbiology. PMID: 33034093.
onlinelibrary.wiley.com/doi/10.1111/mmi.14623
Dubovoy V., Desai P., Hao Z., Cheng C., Verma G., Wojtas L., Brinzari T.V., Boyd J.M., Ma S., Asefa T., Pan L., Synthesis, Characterization, and Antimicrobial Investigation of a Novel Chlorhexidine Cyclamate Complex. 4/2020 ACS Crystal Design and Growth. doi.10.1021/acs.cgd.0c00107
pmc.ncbi.nlm.nih.gov/articles/PMC8159181
Dubovoy V., Nawrocki S., Verma G., Wojtas L., Desi P., Al-Tameemi H., Brinzari T.V., Stranick M., Chen D., Xu S., Ma S., Boyd J.M., Asefa T., Pan L., Synthesis, characterization, and investigation of the antimicrobial activity of cetylpyridinium tetrachlorozincate. 4/2020 American Chemical Society Omega. PMID: 32426592.
pmc.ncbi.nlm.nih.gov/articles/PMC7226859
Price E.E., Boyd J.M., Genetic control of metal ion homeostasis in Staphylococcus aureus. 5/2020 Trends in Microbiology. PMID: 32381454.
pmc.ncbi.nlm.nih.gov/articles/PMC7494629
Rudra, P., Boyd J.M. Metabolic control of virulence factor production in Staphylococcus aureus. 5/2020 Current Opinion in Microbiology. PMID: 32388086.
pmc.ncbi.nlm.nih.gov/articles/PMC7311248
Norambuena J., Miller M., Boyd J.M.*, Barkay T.*, Expression and regulation of the mer operon in Thermus thermophilus. 2/2020 Environmental Microbiology. PMID: 32090420
* co-corresponding authors
enviromicro-journals.onlinelibrary.wiley.com/doi/10.1111/1462-2920.14953
Lab Members
Ph.D. Students
- Hassan Al-Tameemi
- Javiera Norambuena Morales
- Mary Foley
- Hu (Linda) Shuangfang (visiting from South China University of Technology)
M.S. Students
- Adriana van de Guchte
- Siamak Garabaglu
Undergraduate Students
- Juan Cerezo
- Nisa Mohammed
- Srinivas Rajagopalan
- Tarek Abdelazeez
Laboratory Technician
- Mackenzie Purdy