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.

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Selected Publications

• 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., YlaN is an iron(II) binding protein that functions to relieve Fur-mediated repression of gene expression in Staphylococcus aureus. https://www.biorxiv.org/content/10.1101/2023.10.03.560778v1

• 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://journals.asm.org/doi/10.1128/mbio.01350-23

• 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. 9/23 Advanced Science accepted
• 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. PLoS Pathogens. 6/2023 PMID: 37440594 https://pubmed.ncbi.nlm.nih.gov/37440594/
• 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. bioRxiv https://pubmed.ncbi.nlm.nih.gov/37398167/
• 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. PLoS Pathogens. Accepted 5/2023

  https://pubmed.ncbi.nlm.nih.gov/37235600/

•  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). American Chemical Society Applied Materials & Interfaces 3/2023 PMID: 36975176 * co-corresponding authors https://pubs.acs.org/doi/10.1021/acsami.2c19899
• 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. mSphere. 2/2023 PMID: 37017574 https://journals.asm.org/doi/full/10.1128/msphere.00524-22?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org 
• 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. American Chemical Society Omega. 11/2022 PMID: 36506149 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730764/ 
• Andrews T.P., Hoyer J.S., Fahrenfeld N.L., Boyd J.M.*, Duffy S.* Complete genome sequences of five Phietaviruses infecting Staphylococcus aureus. Microbiology Resource Announcements 10/2022 PMID: 36173192 * co-corresponding authors https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9583785/ 
• 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. American Chemical Society Omega12/2021 PMID: 34984275 https://pubs.acs.org/doi/10.1021/acsomega.1c04034 
• Esquilin-Lebron K., Dubrac, S., Barras F., Boyd J.M. Bacterial approaches for assembling iron-sulfur proteins. mBio12/2021 PMID 34781750. https://journals.asm.org/doi/full/10.1128/mBio.02425-21?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org 
  
• 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. Molecular Microbiology. 2021. https://pubmed.ncbi.nlm.nih.gov/33034093/
• 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. Methods in Molecular Biology, 2021 https://pubmed.ncbi.nlm.nih.gov/34292543/
• 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. mBio. 2020 https://journals.asm.org/doi/10.1128/mBio.02555-20
• 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. Applied and Environmental Microbiology 2021. https://journals.asm.org/doi/10.1128/AEM.01108-21?url_ver=Z39.882003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
• Price E.E., Román-Rodríguez F., Boyd J.M., Bacterial approaches to sensing and responding to respiration and respiration metabolites. Molecular Microbiology 2021. https://onlinelibrary.wiley.com/doi/10.1111/mmi.14795
• 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. ACS Infection Disease. 2021 * co-corresponding authors
  https://pubs.acs.org/doi/10.1021/acsinfecdis.1c00265
• 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. Journal of Bacteriology. 2021
  https://journals.asm.org/doi/10.1128/JB.00204-21?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
• 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. mBio. 2021
  https://journals.asm.org/doi/10.1128/mBio.00814-21
• Price E.E., Boyd J.M., Genetic control of metal ion homeostasis in Staphylococcus aureus. Trends in Microbiology, 2020 PMID: 32381454.
• 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. ACS Omega, 2020 PMID: 32426592.
• 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. ACS Crystal Design and Growth, 2020 doi.10.1021/acs.cgd.0c00107
• Tiwari N., López-Redondo M., Miguel-Romero L., Kulhankova K., Cahill M.P., Al-Tameemi H., Herfst C.A., Kirby J.R., Boyd J.M., McCormick J.K., Salgado-Pabón W., Marina A., Schlievert P.M., Fuentes E.J., The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines. Proceedings of the National Academy of Sciences, 2020 PMID: 32354997.
• Rudra, P., Boyd J.M. Metabolic control of virulence factor production in Staphylococcus aureus. Current Opinion in Microbiology, 2020 PMID: 32388086.
• Norambuena J., Miller M., Boyd J.M.*, Barkay T.*, Expression and regulation of the mer operon in Thermus thermophilus. Environmental Microbiology. 2020.
  * co-corresponding authors
• Ferrer-Gonzalez E., Fujita J., Yoshizawa T., Nelson J., Pilch A., Hillman E., Ozawa M., Kuroda N., Al-Tameemi H., Boyd J.M., LaVoie E., Matsumura H., and Pilch D. Structure-Guided Design of a Fluorescent Probe for the Visualization of FtsZ in Clinically Important Gram-Positive and Gram-Negative Bacterial Pathogens. Nature Scientific Reports. 2019.
• Mashruwala A.A., Eilers B.J., Fuchs A., Earle C.A., Van De Guchte A., Copié V., Boyd J.M. The ClpCP complex modulates respiratory, but not fermentative metabolism in Staphylococcus aureus and is regulated in a SrrAB-dependent manner. Journal of Bacteriology. 2019.
• Norambuena J., Hanson T., Barkay T., Boyd J.M., Superoxide dismutase and pseudocatalase increase tolerance to Hg(II) in Thermus thermophilus HB27 by maintaining the reduced bacillithiol pool. mBio. 2019.
• Boyd J.M., Dunn K., Mohammed N., Desai, P., Purdy M., Li W.H., Fourre T., Miksa D., Crane S., Southall M., Fassih A., Propionibacterium acnes Susceptibility to Low-Level 449 nm Blue Light. Lasers in Surgery and Medicine. 2019. PMID: 30919507
• Austin C.M., Garabaglu S., Krute C.N., Ridder M.J., Seawell N.A., Markiewicz M.A., Boyd J.M., Bose J.L. Contribution of YjbIH to virulence factor expression and host colonization in Staphylococcus aureus. Infection and Immunity. 2019. PMID: 30885928
• Bezar I.F., Mashruwala A.A., Boyd J.M., Stock A.M., Drug-like Fragments Inhibit agr-Mediated Virulence Expression in Staphylococcus aureus. Nature Scientific Reports. 2019
• Rosario-Cruz Z.*, Eletsky A., Daigham N.S., Al-Tameemi H.M., Swapna G.V.T., Szyperski T., Montelione G.T., and Boyd J.M. The copBL operon protects Staphylococcus aureus from copper toxicity: Cbl is an extracellular membrane-associated copper-binding protein. Journal of Biological Chemistry. 2019 Jan. PMID: 30655293
  *highlighted by JBC as a must-read article
• Dubovoy V., Ganti A., Zhang T., Al-Tameemi H.M., Cerezo J., Boyd J.M.*, Asefa T.* One-pot hydrothermal synthesis of benzalkonium-templated mesoporous silica antimicrobial agents. Journal of the American Chemical Society. 2018 Oct. PMID: 30260224
  *co-corresponding authors
• Harper L., Balasubramania D., Ohneck E.A., Sause W.E., Chapman J., Mejia-Sosa B.2 Lhakhang T., Heguy A., Tsirigos A., Ueberheide B., Boyd J.M., Lun D.S., Torres V.J. Staphylococcus aureus responds to the central metabolite pyruvate to regulate virulence. mBio. 2018 Jan. PMID: 29362239
• Norambuena J., Wang Y., Hanson T., Boyd J.M., Barkay T. Low molecular weight thiols and thioredoxins are important players in Hg(II) tolerance for Thermus thermophilus HB27. Applied and Environmental Microbiology . 2017.
• Mashruwala A.A., Boyd J.M. Investigating the role(s) of SufT and the domain of unknown function 59 (DUF59) in the maturation of iron-sulfur proteins. Current Genetics. 2017. PMID 28589301
• Mashruwala A.A., Gries C.M., Scherr T.D., Kielian T., and Boyd J.M. SaeRS is responsive to cellular respiratory status and regulates fermentative biofilm formation in Staphylococcus aureus. Infection and Immunity 2017. PMID: 28507069
• Roberts C., Jasim H., Mashruwala A.A., Rosario-Cruz Z., Sause, W., Torres V.J., and Boyd J.M. The Suf iron-sulfur cluster biosynthetic system is essential for Staphylococcus aureus viability and defective Fe-S cluster biosynthesis results in broad metabolic defects and decreased survival in neutrophils. Infection and Immunity. 2017. PMID: 28320837
• Tanner A.W., Carabetta V.J., Martinie R.J., Mashruwala A.A., Boyd J.M., Krebs C., Dubnau D. The RicAFT (YmcA-YlbF-YaaT) complex carries two [4Fe-4S]²⁺ clusters and may respond to redox changes. Molecular Microbiology. 2017. PMID:28295778 DOI
• Mashruwala A.A. Van de Guchte A., Boyd J.M. Impaired respiration elicits SrrAB-dependent programmed cell lysis and biofilm formation in Staphylococcus aureus. eLife. 2017 Feb. PMID:28221135
  Manuscript
  Podcast Discussing the Article
  Insight Article
  Article Digest
• Mashruwala, A. A., Boyd J.M. The Staphylococcus aureus SrrAB regulatory system modulates hydrogen peroxide resistance factors, which imparts protection to aconitase during aerobic growth. PLoS One. 2017 Jan. PMID:28099473
• Mashruwala A.M., and Boyd J.M. De novo assembly of plasmids using yeast recombinational cloning. Methods in Molecular Biology. 2016 Feb. PMID: 26194707
• Rosario-Cruz Z. and Boyd J.M. Physiological roles of bacillithiol in intracellular metal processing. Current Genetics. 2016 Feb. PMID: 26259870
• Mashruwala A.A., Bhatt S., Poudel S., Boyd E.S., and Boyd J.M. The DUF59 containing protein SufT is involved in the maturation of iron-sulfur (FeS) proteins during conditions of high FeS cofactor demand in Staphylococcus aureus. PLoS Genetics. 2016 Aug. PMID: 27517714
• Choby J.E., Mike L.A., Mashruwala A.A., Dutter B.F., Dunman, P.M., Sulikowski G.A., Boyd J.M.*, and Skaar E.P.* A small-molecule inhibitor of iron-sulfur cluster assembly uncovers a link between virulence regulation and metabolism in Staphylococcus aureus in an Sae-dependent manner. Cell Chemical Biology. 2016 Nov. PMID:27773628
  *co-corresponding authors
• Mashruwala A.A., Roberts C., Bhatt S. May K.L., Carroll R.K., Shaw L.N., Boyd J.M. Staphylococcus aureus SufT: an essential iron-sulfur cluster assembly factor in cells experiencing a high-demand for lipoic acid. Molecular Microbiology. 2016 Sep. PMID: 27671355
• Mashruwala A.A., Pang Y.Y., Rosario-Cruz Z., Chahal H.K., Benson M.A., Anzaldi-Mike L.L., Skaar E.P., Torres V.J., Nauseef W.M., Boyd J.M. Nfu facilitates that maturation of iron-sulfur proteins and participates in virulence in Staphylococcus aureus. Molecular Microbiology. 2015 Feb. PMID: 25388433
• Eveleigh D.E., Häggblom M., and Boyd J.M. The early challenges of antibiotic discovery. Microbe. 2015 Nov. 10 (11): 449-450.
• Rosario-Cruz Z., Chahal H.K., Anzaldi-Mike L.L., Skaar E.P., and Boyd J.M. Bacillithiol has a role in Fe-S cluster biogenesis in Staphylococcus aureus. Molecular Microbiology. 2015 Oct. PMID: 26135358
• Tammy M. Joska, T.M., Mashruwala A., Boyd J.M.*, and Belden W.J.*, A universal cloning method based on yeast homologous recombination that is simple, efficient, and versatile. Journal of Microbial Methods. 2014 Jan 10. PMID: 2441681
  *co-corresponding authors
• White M.J., Boyd J.M., Horswill A.R., Nauseef W.M., Phosphatidylinositol-specific phospholipase C contributes to survival of Staphylococcus aureus USA300 in human blood and neutrophils. Infection and Immunity. 2014 Jan 22. PMID: 24452683
• Perrineau M.M, Gross J., Zelzion E., Price D.C. Levitan O., Boyd J.M., Bhattacharya D., Using natural selection to unlock the adaptive potential of microalgal genomes. PLoS One. 2014 Mar 21. PMID: 24658261.
• Boyd E.S., Thomas K.M., Dai Y., Boyd J.M.*, Outten F.W.* Interplay between oxygen and Fe-S cluster biogenesis: Insights from the Suf pathway. Biochemistry. 2014 Sep 11. PMID: 25153801
  *co-corresponding authors
• Yu J., Madsen M.L., Carruthers M.D., Phillips G.J., Kavanaugh J.S., Boyd J.M., Horswill A.R., Minion F.C.. Analysis of autoinducer-2 quorum sensing in Yersina pestis. Infection and Immunity. 2013 Nov 15. PMID: 24247266.
• Price-Whelan A., Poon C.K., Benson M.A., Eidem T.T., Roux C.M., Boyd J.M., Dunman P.M., Torres V.J., Krulwich T.A., Transcriptional profiling of Staphylococcus aureus during growth in 2 M NaCl leads to clarification of physiological roles for Kdp and Ktr K+ uptake systems. MBio. 2013 Aug 20. 4(4). PMID: 23963175.
• Pang Y.Y., Schwartz J., Boyd J.M., Horswill AR, Nauseef W.M., Methionine sulfoxide reductases Protect against oxidative stress in Staphylococcus aureus encountering exogenous oxidants and human neutrophils. Journal of Innate Immunity. 2013 Nov 15. PMID: 24331053
• Walker J.N., Spaulding A., Salgado-Pab?n W., Schlievert P.M., Boyd J.M., Horswill A.R. The Staphylococcus aureus ArlRS two-component system is a novel regulator of agglutination and pathogenesis. PLoS Pathogens. 2013 Dec 9. PMID: 24367264.
  
• Perrineau M.M, Gross J., Zelzion E., Price D.C., Boyd J.M., Bhattacharya D. Evolution of salt tolerance in a laboratory reared population of Chlamydomonas reinhardtii. Environmental Microbiology. 2013 Dec 24. PMID 24373049

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Courses

Undergraduate

• 11:680:481 | Microbial Physiology (56k PDF)

Graduate

• 16:682:503 | Microbial Physiology

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