Blythe Janowiak, Ph.D.
Molecular and Cellular Biology 1, Microbial Ecology
Ph.D., Medical College of Wisconsin
Janowiak's laboratory is interested in how specific Gram-positive pathogenic bacteria
evade the host cell defenses during an infection. By better understanding the biochemical
basis of their toxins and bacterial defenses, researchers can better target these
toxins and defenses in order to weaken the bacteria during an infection. Antibiotic
resistant bacteria are on the rise, and researchers need to develop alternatives to
the common antibiotics.
Specifically, research in her laboratory is focused around Streptococcus agalactiae (Group B Steptococcus, GBS), an important pathogen most known for its role in causing neonatal meningitis. Pregnant mothers testing positive for GBS are given prophylactic antibiotics to help prevent passing on the infection to their babies. However, due to the rampant increase use of antibiotics in animal feed, on vegetables, and in the environment, many bacterial species, including GBS, are becoming resistant to many of the common antibiotics. Therefore, novel antibiotic targets need to be developed. Attractive targets are the primary defenses of GBS against the host immune system. GBS is able to both escape from macrophages and persist inside macrophages for days, due to potent toxins and oxidative stress resistances, respectively. The goals of Janowiak's lab are to 1) explore the biochemical and biophysical mechanisms of the GBS toxins, and 2) understand the role and biochemical basis of the oxidative stress defenses of GBS.
Labs and Facilities
Janowiak welcomes graduate and undergraduate students in my laboratory with interest in the biochemistry of pathogenic bacteria. Research projects include the opportunity to study select Gram-positive pathogens using a variety of biochemical, microbiological, cellular, biophysical, and molecular techniques. Students interested are welcome to contact me about current research opportunities in my laboratory.
Publications and Media Placements
Rajapaksha, M., Lovell, S., Janowiak, B.E., Sun, J., Andra, K.K., Battaile, K.P., and Bann, J.G., pH effects on binding between the anthrax protective antigen and the host cellular receptor CMG2. Protein Science. 21, 1467-1480 (2012).
Janowiak, B.E., Jennings-Antipov, L.D., and Collier, R.J., Cys-Cys crosslinking shows contact between the N-terminus of lethal factor and Phe427 within the anthrax toxin pore. Biochemistry. 50: 3512-3516 (2011).
Wimalasena, D.S., Janowiak, B.E., Lovell, S., Miyagi, M., Sun, J., Zhou, H., Hajduch, J., Pooput, C., Kirk, K.L., Battaile, K.P., Bann, J.G., Evidence That Histidine Protonation of Receptor-Bound Anthrax Protective Antigen Is a Trigger for Pore Formation. Biochemistry. 49: 6973-6983 (2010).
Zornetta, I., Brandi, L., Janowiak, B., Dal Molin, F., Tonello, F., Collier, R.J., Montecucco, C., Imaging the cell entry of the anthrax oedema and lethal toxins with fluorescent protein chimeras. Cell Microbiol. 12: 1435-1445 (2010).
Pentelute BL, Barker AP, Janowiak BE, Kent SB, Collier RJ., A semisynthesis platform for investigating structure-function relationships in the N-terminal domain of the anthrax Lethal Factor. ACS Chem Biol. 2010 Apr 16;5(4):359-64.
Janowiak BE*, Fischer A*, Collier RJ., Effects of introducing a single charged residue into the
phenylalanine clamp of multimeric anthrax protective antigen. J Biol Chem. 2010 Mar
12;285(11):8130-7. Epub 2010 Jan 8.
*both authors contributed equally
Nakashima Y, Nii H, Janowiak BE, Griffith OW, Hibi T., Crystallization and preliminary crystallographic analysis of bifunctional gamma-glutamylcysteine synthetase-glutatione synthetase from Streptococcus agalactiae. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Jul 1;65(Pt 7):678-80. Epub 2009 Jun 27.
Janowiak BE, Finkelstein A, Collier RJ., An approach to characterizing single-subunit mutations in multimeric prepores and pores of anthrax protective antigen. Protein Sci. 2009 Feb;18(2):348-58.
Katayama H*, Janowiak BE*, Brzozowski M, Juryck J, Falke S, Gogol EP, Collier RJ, Fisher MT., GroEL as a molecular
scaffold for structural analysis of the anthrax toxin pore., Nat Struct Mol Biol.
2008 Jul;15(7):754-60. Epub 2008 Jun 22.
*both authors contributed equally
Wimalasena DS, Cramer JC, Janowiak BE, Juris SJ, Melnyk RA, Anderson DE, Kirk KL, Collier RJ, Bann JG., Effect of 2-fluorohistidine labeling of the anthrax protective antigen on stability, pore formation, and translocation. Biochemistry. 2007 Dec 25;46(51):14928-36. Epub 2007 Nov 29.
Janowiak BE, Hayward MA, Peterson FC, Volkman BF, Griffith OW., Gamma-glutamylcysteine synthetase-glutathione synthetase: domain structure and identification of residues important in substrate and glutathione binding. Biochemistry. 2006 Sep 5;45(35):10461-73.
Janowiak BE, Griffith OW., Glutathione synthesis in Streptococcus agalactiae. One protein accounts for gamma-glutamylcysteine synthetase and glutathione synthetase activities. J Biol Chem. 2005 Mar 25;280(12):11829-39. Epub 2005 Jan 10.
Brenot A, King KY, Janowiak B, Griffith O, Caparon MG., Contribution of glutathione peroxidase to the virulence
of Streptococcus pyogenes.
Infect Immun. 2004 Jan;72(1):408-13.