Jeff Boyd

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.

Rios-Delgado G.,  McFarlane R., Zheng V., Kim J., Parker D., Kehl-Fie T., Lalaouna D., Boyd J.M., The iron-regulated small regulatory RNA IsrR modulates expression of genes utilized for dioxygen metabolism and heme synthesis in Staphylococcus aureus. 9/2025  mBio. PMID: 41042061
https://journals.asm.org/doi/10.1128/mbio.01415-25 

Roman-Rodriguez F., Tyagi N., Al-Tameemi H., Boyd J.M. Pseudomonas aeruginosa secreted respiratory toxin HQNO triggers fatty acid accumulation in respiring Staphylococcus aureus, decreasing SaeRS-dependent transcriptional regulation. 9/2025  Journal of Bacteriology. PMID: 41060081
https://journals.asm.org/doi/10.1128/jb.00395-25

Roman Rodriguez F., Tyagi N., Kim J., Parker D., Boyd J.M., An effective response to respiratory inhibition by a Pseudomonas aeruginosa excreted quinoline promotes Staphylococcus aureus fitness and survival in co-culture. 9/2025 Journal of Bacteriology. PMID: 41114581
https://journals.asm.org/doi/10.1128/jb.00101-25

Boyd J.M., Rios-Delgado G., Esquilín-Lebrón K., Ryan Kaler K., Mereddy G., Norambuena J., Zheng V., Beavers W.N., Kim J., Parker D., Skaar E.P., Carrol. R.K., Yang J.H. Fermentative growth decreases the iron demand of Staphylococcus aureus. 9/2025 Journal of Inorganic Biochemistry. PMID: 41032936
https://www.sciencedirect.com/science/article/pii/S016201342500265X?via%3Dihub

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. 8/2025  PMID: 40745169
https://pmc.ncbi.nlm.nih.gov/articles/PMC12313914/

Charbonnier M., Probst S., Racine H., Radin J.N., Rios-Delgado G., Laster H.M., Mazgaj R., Kohl M., Blum M., Marchand V., Chicher J., Marzi S., Romby P., Tree J., Waldron K.J., Boyd J.M., Dutheil J.Y., Kehl-Fie T.E., Lalaouna D., A Zur-dependent regulatory RNA involved in maintaining zinc homeostasis in Staphylococcus aureus. 8/2025 bioRxiv.
https://www.biorxiv.org/content/10.1101/2025.08.23.671911v1

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
https://pubmed.ncbi.nlm.nih.gov/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
 https://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
https://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
https://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
https://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
https://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.
https://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.
https://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
https://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
https://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
https://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
https://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
https://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
https://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
https://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
https://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
https://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.
https://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.
https://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
https://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.
https://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.
https://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.
https://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 to Gram-positive pathogens. 10/2020 mBio. PMID: 33109764.
https://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.
^{https://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
https://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.
https://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.
https://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.
https://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
https://enviromicro-journals.onlinelibrary.wiley.com/doi/10.1111/1462-2920.14953

Undergraduate

• 11:680:481 | Microbial Physiology

Graduate

• 16:682:503 | Microbial Physiology

Current Members:
Ph.D. students

• Gustavo Rios
• Franklin Roman Rodriguez
• Hannah Bovermann
• Nupur Tyagi
• Liangyu Lyu

M.S. students:

• Navitri Naidu
• Matthew Pagoria

Undergraduate students:

• Tedros Abera
• Vincent Zheng

Lab Alumni:

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