The overall interest of the lab
is the study of the pathogenesis of bacterial meningitis,
specifically interactions between Group B Streptococcus
(GBS) and brain microvascular endothelial cells
(BMEC) that comprise the human blood-brain barrier.
Our research seeks to identify GBS genes and gene
products responsible for BMEC cellular invasion,
characterize the innate immune response of the blood-brain
barrier to bacterial pathogens and understand the
contribution of bacterial surface filamentous structures,
called pili, to the disease process.
Lab
website
Publications:
Maisey HC, Quach D, Hensler ME, Liu
GY, Nizet V. and Doran, K.S. 2007. A group B streptococcal
pilus protein promotes virulence and phagocyte resistance.
(manuscript submitted).
Carlin AF, Uchiyama S, Khosravi A, Quach D, Hightower
G, Mitchell TJ, Varki A, Doran, K.S. and Nizet,
V. 2007. The surface-anchored NanA protein promotes
pneumococcal blood-brain barrier invasion. (manuscript
submitted).
Hensler, M.E., Quach, D., Hsieh C.-J., Doran, K.S.
and Nizet, V. 2007. CAMP factor is not essential
for systemic virulence of Group B streptococcus.
J. Microb Pathog (in press).
Maisey, H.C., Hensler, M. E., Nizet, V. and Doran,
K.S. 2007. Group B streptococcal pili proteins contribute
to adherence and invasion of brain microvascular
endothelial cells. J. Bacteriol. 189: 1464-1467.
Kwinn, L.A., Aziz, R.K., Khosravi, A., Timmer, A.M.,
Taylor, W.L., Kubal, M., Doran, K.S., Kotb, M.,
and Nizet, V. 2007. Genetic Characterization and
virulence role of the Ralp3/Lsap locus upstream
of the streptolysin S operon in invasive M1T1 group
A streptococcus. J. Bacteriol. 189: 1322-1329.
Maisey, H.C., Hensler, M. E., Khosravi, A., Liu,
G.Y., Nizet, V. and Doran, K.S. 2006. A single streptococcal
gene can confer innate immune resistance and virulence
to a nonpathogenic bacterium. International Congress
Series 1289: 223-226.
Doran, K.S., Engelson, E.J., Khosravi, A., Maisey,
H.C., Fedtke, I., Equils, O., Michelsen, K.S., Arditi,
M., Peschel, A., and Nizet, V. 2005. Blood-brain
barrier invasion by group B streptococcus
depends upon proper cell-surface anchoring of lipoteichoic
acid. J. Clin. Invest. 115: 2499-2507.
Liu, G.Y., Doran, K.S., Lawrence, T., Turkson, N.,
Puliti, M., Tissi, L., Nizet, V. 2004. Sword and
shield: linked group B streptococcal B-hemolysin/cytolysin
and carotenoid pigment act synergistically to subvert
phagocytic defenses. Proc. Natl. Acad. Sci. 101:
14491-14496.
Doran, K.S. and Nizet, V. 2004. Molecular pathogenesis
of neonatal group B streptococcal infection: no
longer in its infancy. Mol. Microbiol. 54: 23-31.
Doran, K.S., Liu, G.Y., Nizet, V. 2003. Group B
streptococcal B-hemolysin/cytolysin activates neutrophil
signaling pathways in brain endothelium and contributes
to development of meningitis. J. Clin. Invest. 112:
736-744.
Doran, K.S., Benoit, V.M., Gertz, R.E., Jr., Beall,
B., Nizet, V. 2002. Late-onset group B streptococcal
infection in identical twins: insight to disease
pathogenesis. J. Perinatol. 22: 326-330.
Doran, K.S., Chang, J.C.W., Benoit, V.M., Eckmann,
L., Nizet, V. 2002. Group B streptococcal B-hemolysin/cytolysin
promotes invasion of human lung epithelial cells
and the release of interleukin-8. J. Infect. Dis.185:
196-203.
Doran, K.S., Helinski, D.R., and Konieczny, I. 1999.
Host-dependent requirement for specific DnaA boxes
for plasmid RK2 replication. Mol. Microbiol. 33:
490-498.
Doran, K.S., Helinski, D.R., and Konieczny, I. 1999.
A critical DnaA box directs the cooperative binding
of the Escherichia coli DnaA protein to
the plasmid RK2 replication origin. J. Biol. Chem.
274: 17918-17923.
Doran, K.S., Konieczny, I., and Helinski, D.R. 1998.
Replication origin of the broad host range plasmid
RK2: Positioning of various motifs is critical for
initiation of replication. J. Biol. Chem. 273: 8447-8453.
Konieczny,I., Doran, K.S., Helinski, D.R., and Blasina,
A. 1997. Role of TrfA and DnaA proteins in origin
opening during initiation of DNA replication of
the broad host range plasmid RK2. J. Biol. Chem.
272: 20173-20178.