Pilus assembly of Gram-positive pathogens, biofilm formation and bacterial pathogenesis
The Ton-That laboratory is interested in investigating: (1) Molecular assembly on the cell surface of Gram-positive bacteria, (2) Post-translocational protein folding in Gram-positive bacteria, (3) Development of a cell-based assay to discover new bacterial anti-infective agents, and (4) Virulence determinants of Fusobacterium nucleatum.
Several outstanding questions (Black Boxes) are currently being addressed by various members in the lab: (1) How pilins are folded after membrane translocation, (2) What factors control the switch between pilus polymerization and cell wall anchoring, (3) How various pilins mediate bacterial pathogenesis and biofilm formation, and (4) How CafA mediates pilus assembly and cellular interactions.
Abu Amar Al Mamun
Research Scientist (Ph.D., Okayama University, Okayama, Japan)
The development of oral biofilm known as dental plaque requires interactions between oral microbes. The oral biofilm begins with the attachment of early colonizers Actinomyces and Streptococcus. Actinomyces oris is a key gram-negative colonizer of the oral cavity. A. oris enhances growth of a three-species biofilm composed Fusobacterium nucleatum, Streptococcus oralis and A. oris. A. oris can also serve as a bridge between Streptococcus gordonii and F. nucleatum. This adherence of Actinomyces is mainly attributed to two antigenically and functionally distinct types of fimbrae present on the bacterial surface.
The sortase SrtA, a cysteine-transpeptidase conserved in Gram-positive bacteria plays central roles in the cell wall anchoring of fimbrial polymers as well as numerous surface proteins that facilitate bacterial pathogenesis and fitness. The housekeeping sortase SrtA of A. oris is essential for cell viability. Using Tn-5 transposon mutagenesis, this lab identified 5 sets of genetic suppressors for SrtA essentiality. Two of the suppressors include genes of a locus encoding AcaC and a LytR-CpsA-Psr (LCP)-like protein. AcaC is highly glycosylated when SrtA is depleted, and this glycosylation is dependent on LCP.
To understand the mechanisms of assembly of A. oris surface structures and their interactions, I have been involved in the following projects:
- Characterization of a suppressor mutant in the operon for the genes ANA2669-2672 of unknown function for housekeeping sortase SrtA in A. oris.
- Identification of glycosylation sites in AcaC in A. oris
- Characterization of LCP-dependent glycosylation of AcaC
- Al Mamun, AA and SM Rosenberg. 2015. New DNA damage-response activators and spontaneous DNA breaks inducers in a large gene network for stress-induced mutation. Manuscript in preparation to submit in Plos Genetics.
- Al Mamun, AA, Cancer Genome Atlas Research Network. 2015. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma. Under review in New England Journal of Medicine.
- Al Mamun, AA, M-J Lombardo, AM Lisewski, C Shee, C Gonzalez, D Lin, RB Nehring, C Saint Ruf, JL Gibson, RL Frisch, O Lichtarge, PJ Hastings, SM Rosenberg. 2012. Identity and function of a large gene network underlying mutagenic repair of DNA breaks. Science 338:1344-13448. This article is featured in the Leading Edge of the Journal Cell. Genome Instability: Mapping a Mutagenic Network. Cell 152:9-10, Jan 17, 2013.
- Al Mamun, AA and MZ Humayun. 2009. Spontaneous mutagenesis is elevated in protease-defective cells. Molecular Microbiology 71:629-39.
- Al Mamun, AA. 2007. Elevated expression of DNA polymerase II increases spontaneous mutagenesis in Escherichia coli. Mutation Research. Mutation Research 6251:29-39.
- Al Mamun, AA, S Gautam and MZ Humayun. 2006. Hypermutagenesis in mutA cells is mediated by corrupted polymerase and is accompanied by replication fork collapse. Molecular Microbiology 62:1752-1763.
- Al Mamun, AA and MZ Humayun. 2006. Escherichia coli DNA polymerase II can efficiently bypass 3, N4-ethenocytosine lesions in vitro and in vivo. Mutation Research 593:164-176.
- Al Mamun, AA, KJ Marians and MZ Humayun. 2002. DNA polymerase III from Escherichia coli cells expressing mutA mistranslator tRNA is error-prone. Journal of Biological Chemistry 277:46319-46327.
- A Tominaga, MAH Mahmoud, Al Mamun, AA and T Mukaihara. 2001. Characterization of cryptic flagellin genes in Shigella boydii and Shigella dysenteriae. Genes and Genetic System 76:111-20.
- Al Mamun, AA, RS Yadava , L Ren, and MZ Humayun. 2000. The Escherichia coli UVM response is accompanied by an error-prone DNA replication activity demonstrable in vitro. Molecular Microbiology 38:368-380.
- Ren, L, Al Mamun, AA and MZ Humayun. 2000. Requirement for homologous recombination functions for expression of the mutA mistranslator tRNA-induced mutator phenotype in Escherichia coli. Journal of Bacteriology 182 (5):1427-1431.
- Al Mamun, AA, MS Rahman and MZ Humayun. 1999. Escherichia coli cells bearing mutA , a defective glyV tRNA gene, express a recA-dependent error-prone DNA replication activity. Molecular Microbiology 33(4):732-740.
- Ren, L, Al Mamun, AA and MZ Humayun. 1999. The mutA mistranslator tRNA induced mutator phenotype requires recA and recB genes but not the derepression of lexA regulated functions. Molecular Microbiology 32(3):607-615.
- Al Mamun, AA, A. Tominaga, and M. Enomoto. 1997. Cloning and characterization of the region III flagellar operons of the four Shigella subgroups: genetic defects that cause loss of flagella of Shigella boydii and Shigella sonnei. Journal of Bacteriology 179:4493-4500.
- Al Mamun, AA, A Tominaga, and M Enomoto. 1996. Detection and characterization of the flagellar master operon in the four Shigella subgroups. Journal of Bacteriology 178:3722-3726.
- Nur-E-Kamal MS, Al Mamun, AA and ZU Ahmed. 1994. Molecular cloning of the wild-type and mutant thyA gene from Shigella flexneri Y. Microbiology Immunology 38(4):309-12.
Chungyu (Julie) Chang
Senior Research Associate (Ph.D., Texas A&M University)
Pili have been demonstrated to be virulence factors in Gram positive bacteria. The diphtheria causative agent Corynebacterium diphtheriae assembles three distinct pilus types, i.e. the SpaA, SpaD, and SpaH pili. Well studied is the SpaA pilus, which is encoded by the spaA–srtA–spaB–spaC gene cluster. In C. diphtheriae, pilus assembly is a collaborated task between pilus-specific sortases and the house-keeping sortase SrtF. For example, pilin-specific sortase SrtA catalyzes pilus polymerization of SpaA/C pilins, whereas SrtF anchors the resulting pilus polymer to the cell wall via the pilus base SpaB. However, SrtA is dispensable for pilus polymerization of the SpaD and SpaH-pilus types. What determines substrate specificity of these sortase enzymes is not well understood. It has been demonstrated that the LPxTG motif within a cell wall sorting signal of pilin substrates plays a major role in determining the specificity of sortases. Elucidating additional elements contributed to specific activities displayed by various sortases is one of my research projects.
- Sanchez BC, Chang C., Wu, C., Tran, B., Ton-That, H.(2017) Electron transport chain is biochemically linked to pilus assembly required for polymicrobial interactions and biofilm formation in the Gram-positive Actinobacterium Actinomyces oris. MBio. 20; 8(3)
- Montealegre, M.C., Singh, K.V., Somarajan, S.R., Yadav, P., Chang C., Spencer, R., Sillanpää, J., Ton-That, H., Murry, B.E. (2016) Role of the Emp Subunite of Enterococcus faecium in biofilm formation, adherence to host extracellular matrix components and experimental infection. Infect Immun. 22;84(5):1491-500
- Echelman, D., Alegre-Cebollada, J., Badilla, C.L., Chang C, Ton-That, H., Fernández, J.M. (2016) Cna-A domains in bacterial pili are efficient dissipaters of large mechanical shocks. Proc Natl Acad Sci 113(9):2490-5
- Reardon-Robinson, M.E., Osipiuk, J., Jooya, N., Chang C, Joachimiak, A., Das, A.,Ton-That, H. (2015) A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence. Mol Microbiol 98(6):1037-50
- Reardon-Robinson, M. E., Osipiuk, J., Chang, C., Wu, C., Jooyna, N., Joachimiak, A., Das, A., and Ton-That, H. (2015) A disulfide bond-forming machine is linked to the sortase-mediated pilus assembly pathway in the Gram-positive bacterium Actinomyces oris. J Biol Chem 290(35):21393-405
- Kang, H.J., Paterson, N.G., Kim, C.U., Middleditch, M., Chang, C., Ton-That, H., and Baker E.N.(2014) A slow-forming isopeptide bond in the structure of the major pilin SpaD from Corynebacterium diphtheriae has implications for pilus assembly. Acta Crystallogr D Biol Crystallogr. 70(Pt 5):1190-201
- Reardon-Robinson, M., E, Wu C., Mishra A., Chang C., Bier N., Das A., and Ton-That H. (2014) Pilus hijacking by a bacterial coaggregation factor critical for oral biofilm development. PNAS 111(10):3835-40
- Broadway, M., Rogers,E., Chang, C., Huang,I-H., Dwivedi, P., Yildirim,S., Schmitt, M., Das, A., and Ton-That, H. (2013) Pilus gene pool variation and the virulence of Corynebacterium diphtheriae clinical isolates during infection of a nematode” Bacteriol 195(16):3774-83
- Sillanpää, J., Chang, C., Singh, K. V., Nallapareddy, S. R., Montealegre, M. C., Harvey, B. R., Ton-That, and Murray, B.E. (2013) Contribution of individual Ebp pilus subunits of Enterococcus faecalis OG1RF to pilus architecture, biofilm and urinary tract infection. PLoS One 11;8(7):e68813.
- C., Hung, I-H, Hendrickx, A. and Ton-That, H. (2013) Book Chapter: Gram-positive pilus visualization in The Bacterial Cell Surface: Methods and Protocols, series of Methods in Molecular Biology 966, Humana Press
- Chang, C., Mandlik, A. and Ton-That, H. (2011) Cell surface display of minor pilin adhesins in the form of a simple heterodimeric assembly in Corynebacterium diphtheriae. Mol Microbiol 79(5):1236-47
- Chang, C., Kamp, P. and Molineux, I. (2009) Gp15 and gp16 cooperate in translocating bacteriophage T7 DNA into the infected cell. Virology 398 (2010) 176–186
- Blasi, U., Fraisl , P., Chang, C., Zhang, N. and Young, R. (1999) The C-terminal sequence of the lambda holing constitutes a cytoplasmic regulatory domain. Bacteriol 181(9): 2922-2929
- Chang, C. and Bayley, H. (1998) Caged catalytic subunit of cAMP-dependent protein kinase. American Chemical Society 120(30): 7661-7662
- Bayley, H., Chang, C., Miller, W.T., Niblack, B. and Pan, P. (1998) Caged peptides and proteins by targeted chemical modification. Methods in Enzymology 291:117-135
- Smith, D.L., Chang, C., Young, R. (1998) The lambda holing accumulated beyond the lethal triggering concentration under hyperexpression conditions. Gene Expression 7(1): 39-52
- Chang, C., Niblack, B., Walker, B. and Bayley, H. (1995) A photogenerated pore-forming protein. Chemistry & Biology 2(6): 391-400
- Chang, C., Nam, K. and Young, R. (1995) S gene Expression and the timing of lysis by bacteriophage lambda. J Bacteriol 177(11): 3283-3294
- Johnson-Boaz, R., Chang, C. and Young, R. (1994) A dominant mutation in the bacteriophage lambda S gene causes premature lysis and absolute defective plating phenotype. Mol Microbiol 13(3): 495-504
- Chang, C., Nam, K., Blasi, U. and Young, R. (1993) Expression of two bacteriophage lambda S proteins in vivo. Gene 133(1): 9-16
- Blasi, U., Chang, C., Zagotta, M.T., Nam, K. and Young, R. (1990) The lethal lambda S gene encodes its own inhibitor. EMBO 9(4): 981-989
Truc T. Luong
Postdoctoral Fellow (Ph.D., Sungkyunkwan University, South Korea)
Disulfide bond-forming machines that contribute to protein folding, stabilizing structures and degradation-protection are well-characterized in eukaryotes and Gram-negative bacteria. In Escherichia coli, a disulfide bond-forming machine is comprised of a pair of oxidoreductase enzymes DsbA and DsbB. The periplasmic enzyme DsbA catalyzes disulfide bond formation, whereas DsbB recharges DsbA. How disulfide bonds are formed in Gram-positive bacteria is less well understood. Recently, we report the biochemical characterization of Actinomyces oris VKOR, which displays a similar topological arrangement as Mycobacterium tuberculosis VKOR. A. oris VKOR harbors 4 redox active cysteine residues, forming two pairs of redox centers (C93/C101 and C175/C178), with the latter constituting the redox active CXXC motif. Through this mutational analysis, we were able to isolate an MdbA-VKOR intermediate, in which the C93 residue of VKOR is postulated to form a mixed disulfide bond with MdbA. MtbVKOR can rescue A. oris ∆vkor mutant defects. Therefore, we propose a model of VKOR-mediated reactivation of MdbA that appears to be conserved in Actinobacteria. My research is continuing identify molecular mechanisms of disulfide bond formation in different Gram-positive bacteria and structural analysis of this machinery to broaden understanding about disulfide bond proteins.
- Luong TT, Reardon-Robinson M, Siegel S, Ton-That H (2017). Reoxidation of the Thiol-Disulfide Oxidoreductase MdbA by a bacterial Vitamin K Epoxide Reductase in the biofilm-forming Actinomyces oris. Journal of Bacteriology.DOI: 10.1128/JB.00817-16.
- Kim GL, Lee S, Luong TT, Nguyen C, Park S, Pyo S, Rhee DK (2017). Effect of decreased BCAA synthesis through disruption of ilvC gene on the virulence of Streptococcus pneumoniae. Archives of Pharmacal Research. DOI: 10.1007/s12272-017-0931-0
- Nguyen C, Luong TT, Lee S, Kim GL, Pyo S, Rhee DK (2016). ATF3 provides protection from Staphylococcus aureus and Listeria monocytogenes infections. FEMS Microbiology Letters. DOI: 10.1093/femsle/fnw090
- Nguyen CT, Luong TT, Lee SY, Kim GL, Kwon H, Lee HG, Park CK, Rhee DK (2015). Panax ginseng aqueous extract prevents pneumococcal sepsis in vivo by potentiating cell survival and diminishing inflammation. Phytomedicine 22(11):1055-61.
- Nguyen CT, Luong TT, Kim GL, Pyo S, Rhee DK (2015). Korean Red Ginseng inhibits apoptosis in neuroblastoma cells via estrogen receptor β-mediated phosphatidylinositol-3 kinase/Akt signaling. J Ginseng Res. 39(1):69-75.
- Nguyen CT, Kim EH, Luong TT, Pyo S, Rhee DK (2015). TLR4 mediates pneumolysin-induced ATF3 expression through the JNK/p38 pathway in Streptococcus pneumoniae-infected RAW 264.7 cells. Mol Cells. 38(1):58-64.
- Luong TT, Kim EH, Bak JP, Nguyen CT, Choi S, Briles DE, Pyo S, Rhee DK (2015). Ethanol-induced alcohol dehydrogenase E (AdhE) potentiates pneumolysin in Streptococcus pneumoniae. Infect Immun. 83(1):108-19.
- Thach TT, Luong TT, Lee S, Rhee DK (2014). Adenylate kinase from Streptococcus pneumoniae is essential for growth through its catalytic activity. FEBS Open Bio. 4:672-82.
- Nguyen CT, Le NT, Tran TD, Kim EH, Park SS, Luong TT, Chung KT, Pyo S, Rhee DK (2014). Streptococcus pneumoniae ClpL modulates adherence to A549 human lung cells through Rap1/Rac1 activation. Infect Immun. 82(9):3802-10.
- Nguyen CT, Kim EH, Luong TT, Pyo S, Rhee DK (2014). ATF3 confers resistance to pneumococcal infection through positive regulation of cytokine production. J Infect Dis. 210(11):1745-54.
Graduate Student (M.S., New York Medical College)
Pathogenic bacteria synthesize and secrete virulence factors such as pilus structural components that facilitate colonization of their host and infection. Many of these virulence factors are transported across the cytoplasmic membrane via the general secretion system (Sec) as unfolded precursors. How the unfolded proteins gain their native conformation is not well understood in Gram-positive bacteria. We have recently shown in the oral biofilm forming Actinomyces oris that disulfide bond formation is essential for post-translocational protein folding. This process is catalyzed by a pair of thiol-disulfide oxidoreductases MdbA and VKOR. I am interested in elucidating the mechanisms of MdbA-mediated oxidative protein folding, the coupling of this pathway to the electron transport chain, and its role in pathogenesis. It appears that the oxidative protein folding pathway is common in the Gram-positive actinobacteria including Corynebacterium diphtheriae and Mycobacterium tuberculosis, hence an attractive target for antimicrobials.
- Sanchez BC, Chang C, Wu C, Tran B, and Ton-That H (2017). Electron transport chain is biochemically linked to pilus assembly required for polymicrobial interactions and biofilm formation in the Gram-positive actinobacterium Actinomyces oris. mBio, 8(3):e00399-17.
- Rabadi, SM., Sanchez BC, Varanat, M., Ma, Z., Catlett, S., Melendez, j., Malik, M. and Bakshi, CS (2016). Antioxidant Defenses of Francisella tularensis Modulate Macrophage Function and Production of Proinflammatory Cytokines. J Biol Chem, 291(10):5009-21.
- Sanchez BC, Montilla N., Redondo C., Torres, L (2008). Genotypification of multirresistant Acinetobacter baumannii isolated in Dr. Domingo Luciani Hospital of Caracas. Act Cient de la Soc Venz de Bioanal Espec, 11(2): 49-56
Graduate Student (B.S.; St. Edwards University)
The role of changes in the human microbiota and their role in creating a disease-permissive environment are poorly understood. Fusobacterium nucleatum is a normal member of the gut flora, but has also been associated with the poor clinical outcome when it is overrepresented in colorectal cancer patients, has been implicated in preterm birth and contributes to oral disease. By studying the interaction between the gut flora and host cells, we hope to probe the ways that gut health can enhance or promote cancer development. My project examines the role of methionine sulfoxide reductase AB (MsrAB) and its response regulator system in evading immune cell mediated killing via the oxidative burst. By utilizing a mouse model of preterm birth and various in vitro assays, I hope to elucidate the role F. nucleatum plays in human disease.
- Syapin PJ, Martinez JM, Curtis DC, Marquardt PC, Allison CL, Groot JA, Baby C, Al-Hasan YM, Segura I, Scheible MJ, Nicholson KT, Redondo JL, Trotter DRM, Edwards DS, Bergeson SE (2016) Effective Reduction in High Ethanol Drinking by Semisynthetic Tetracycline Derivatives. Alcohol Clin Exp Res. 40(12):2482-2490.
- Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, Wu CC, LeBleu VS, Kalluri R (2015) Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 527(7579):525-530.
- Thibodeau RB, Ornelas LC, Romero J, Memos N, Scheible M, Avila A, Schumacher A, Navarro A, Zimmermann K, Cuenod BA, Frohardt RJ, Guarraci FA (2013) Acute withdrawal but not long-term withdrawal from methamphetamine affects sexual behavior in female rats. Pharmacol Biochem Behav. 103(4):701-9.
Sara D. Siegel
Graduate Student (B.S.; University of Florida, Gainesville)
Accumulation of dental plaque over time can lead to many dental-related diseases, such as dental caries and periodontitis. Dental plaque is a multispecies biofilm initiated when primary bacterial colonizers bind the tooth surface and interact with species that otherwise cannot, to eventually build a polymicrobial community. Actinomyces oris is a Gram-positive, primary colonizer that uses cell surface proteins, such as pili, for attachment and biofilm formation. My projects focus the molecular characterization of cell surface proteins that contribute to oral niche of A. oris.
I’m currently working on two projects. The first is characterizing the molecular details of an LCP protein, and its unique contribution to protein glycosylation in A. oris strain MG1. The second project is elucidating the binding domain of a pilus-associated protein – CafA, and how this protein contributes to interkingdom adherence and whether the presence and role of CafA is conserved in clinical isolates of oral Actinomyces. Additionally, I’m interested in investigating how a non-cognate pilus substrate, CafA, is elaborated onto type 2 pili.
- Luong TT, Reardon-Robinson M, Siegel SD, Ton-That H (2017). Reoxidation of the Thiol-Disulfide Oxidoreductase MdbA by a bacterial Vitamin K Epoxide Reductase in the biofilm-forming Actinomyces oris. Journal of Bacteriology, 199(10):817-16. PubMed PMID: 28289087.
- Siegel SD, Liu J, Ton-That H (2016). Biogenesis of the Gram-positive bacterial cell envelope. Curr Opin Microbiol, 34:31-37. PubMed PMID: 27497053.
- Siegel SD, Wu C, Ton-That H (2016). A Type I Signal Peptidase Is Required for Pilus Assembly in the Gram-Positive, Biofilm-Forming Bacterium Actinomyces oris. J Bacteriol.;198(15):2064-73. PubMed PMID: 27215787; PubMed Central PMCID: PMC4944219.
- Siegel SD, Reardon ME, Ton-That H (2016). Anchoring of LPXTG-Like Proteins to the Gram-Positive Cell Wall Envelope. Curr Top Microbiol Immunol.; PubMed PMID: 27097813.
- Hu H, Liu Y, Zhou Q, Siegel SD, Li Z (2015). The Centriole Cartwheel Protein SAS-6 in Trypanosoma brucei Is Required for Probasal Body Biogenesis and Flagellum Assembly. Eukaryot Cell. 14(9):898-907
- Brown LM, Corrado MM, van der Ende RM, Derks TGJ, Chen MA, Siegel SD, Hoyt Kate, Correia CE, Lumpkin C, Flanagan TB, Carreras CT, Weinstein DA (2015). Evaluation of glycogen storage disease as a cause of ketotic hypoglycemia in children. J Inherit Metab Dis. 38(3):489-93.
- Tsiliandis LA, Fiske LM, Siegel SD, Lumpkin C, Wasserstein M, Weinstein DA (2013). Aggressive therapy improves cirrhosis in glycogen storage disease type IX. Molecular Genetics and Metabolism, 109(2):179-82.
- Wrench AP, Gardner CL, Siegel SD, Pagliai F, Gonzales CF, Lorca GL (2013). MglA/SspA interactions are modulated by inorganic polyphosphate. PLoS One, 8(10):e76428.
Luis Alberto Vega
Postdoctoral Fellow (Ph.D., Washington University School of Medicine, St. Louis)
The Gram-negative anaerobe Fusobacterium nucleatum is a key colonizer in the development of oral biofilms or dental plaque and in most humans is associated with periodontal disease. Recently, F. nucleatum has been linked to other important diseases with life-threatening consequences. The abundance of F. nucleatum has been associated with adenomas and adenocarcinoma tissues in colorectal carcinogenesis, as well as reduced survival of colorectal cancer (CRC) patients and increased chemoresistance of CRCs.F. nucleatum infection is also a factor in adverse pregnancy outcomes including neonatal sepsis, bacteremia, preterm birth, inflammation of fetal membranes, and preeclampsia. My project aims to characterize F. nucleatum factors associated with the development of these diseases with the goal of identifying targets for therapeutic treatment. The focus of the research is on basic biological processes of F. nucleatum that novel genetic tools developed in the lab are allowing us to investigate.
- Vega LA, Vega LA, Valdes KM, Sundar GS, Belew AT, Islam E, Berge J, Curry P, Chen S, El-Sayed NM, Le Breton Y, McIver KS. (2017). The transcriptional regulator CpsY is important for innate immune evasion in Streptococcus pyogenes. Infect Immun 85:e00925-16.
- Valdes KM, Sundar GS, Vega LA, Belew AT, Islam E, Binet R, El-Sayed NM, Le Breton Y, McIver KS. (2016). The fruRBA operon is necessary for Group A Streptococcal growth in fructose and for resistance to neutrophil killing during growth in whole human blood. Infection and Immunity 84 (4). 1016-31. PMID: 26787724.
- Vega LA, Malke H, McIver KS. (2016). Virulence-Related Transcriptional Regulators of Streptococcus pyogenes. Chapter In: Ferretti JJ, Stevens DL, Fischetti VA, editors. Streptococcus pyogenes: Basic Biology to Clinical Manifestations [Internet]. Oklahoma City (OK): University of Oklahoma Health Sciences Center; 2016-. PMID: 26866215.
- Vega LA, Port GC, Caparon MG. (2013). An Association Between Peptidoglycan Synthesis and Organization of the Streptococcus pyogenes ExPortal. mBio 4(5):e0058-513. PMCID: PMC3781834.
- Vega LA, Caparon MG. (2012). Cationic antimicrobial peptides disrupt the Streptococcus pyogenes ExPortal. Molecular Microbiology, 85: 1119-1132. PMCID: PMC3646575.
- Rosch JW, Vega LA, Beyer JM, Lin A, Caparon MG. (2008). The signal recognition particle pathway is required for virulence in Streptococcus pyogenes. Infection and Immunity 76, 2612-9. PMCID: PMC2423074
- Chiranand W, McLeod I, Zhou H, Lynn JJ, Vega LA, Myers H, Yates JR 3rd, Lorenz MC, Gustin MC. (2008). CTA4 transcription factor mediates induction of nitrosative stress response in Candida albicans. Eukaryotic Cell 7, 268-78.
- Chávez V, Mohri-Shiomi A, Maadani A, Vega LA, Garsin DA. (2007). Oxidative stress enzymes are required for DAF-16-mediated immunity due to generation of reactive oxygen species by Caenorhabditis elegans. Genetics 176, 1567-77.
- Ullmann, BD, Myers H, Chiranand W, Lazzell AL, Zhao Q, Vega LA, Lopez-Ribot JL, Gardner PR, Gustin, MC. (2004). Inducible defense mechanism against nitric oxide in Candida albicans. Eukaryotic Cell 3, 715-23.