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My
research is primarily concerned with secondary
pathogens of the respiratory tract. Pseudomonas
aeruginosa, has been of particular concern
because of the high mortality rates associated
with hospital-acquired infections and the high
incidence in cystic fibrosis patients. More recently
we have expanded our interests to other Gram-negative
bacteria.
Recent investigations have concerned identification of the receptors on eukaryotic
cells for bacteria. The primary interest has been identification of receptors
for Pseudomonas aeruginosa. Two classes of receptors have been identified.
We are currently trying to identify the bacterial adhesins responsible for the
binding. At least two adhesins have been characterized: pili and flagella. The
role of pili has been documented by several investigators. How flagella may function
as an adhesin is less clear, but our results indicate that it is required for
adherence. We have hypothesized that after the organisms have attached to cells
by contractile pili, they are brought to the cell surface where secondary adhesins
create a stronger attachment. Flagellin appears to be a major secondary adhesin.
An exciting finding that may be related to the targeting of the flagellin is
posttranslational modification of flagellin. A segment of DNA located downstream
of the flagellin gene appears to be involved in the modification of flagellin.
This process is distinct from the phosphorylation of flagellin that has been
noted by others, and may involve glycosylation--a rare event in bacteria. The
regulation and significance of the modificationare a major areas of focus.
An new area of investigation is genetic immunization to prevent the occurence
of secondary infection following traumatic injury. Preliminary data using the P.
aeruginosa flagellin gene in a eucaryotic expression system indicates that
we can induce a strong immune response to bacterial antigens following injection
of the plasmid DNA. Current studies are concentrating on defining the optimum
conditions for immunization and determining the efficacy of these vaccines.
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Baker,
N. and Verran, J. (2004). The future
of Microbiology Laboratory Classes: Wet,
dry or in combination. Nature Rev. Microbiol.
2 :338-342.
Denis-Mize KS, Price BM, Baker N.R.,
Galloway DR. 2000. Analysis of immunization
with DNA encoding Pseudomonas aeruginosa
exotoxin A. FEMS Immunol Med Microbiol.
27:147-54.
Wahl, S. and Baker, N.R.
Identification of a locus involved in the
posttranslational modification of flagellin
from Pseudomonas aeruginosa. Molecular
Microbiology - In preparation
Wahl, S. and Baker, N.R.
Analysis of type a flagellin from Pseudomonas
aeruginosa strain PAO1. In preparation.
Baker, N.R., Gehring, K.
and Wahl, S. Evidence for a direct role
of flagellin in the adherence of Pseudomonas
aeruginosa to glycosphingolipids. In
preparation.
Baker,
N. R. 1992. Mucosal adherence of
Pseudomonas aeruginosa. In R.B.Fick
(ed.), Pseudomonas aeruginosa the opportunist:
pathogenesis and disease. CRC Press, Inc.
Baker,
N.R., V. Minor, C. Deal, M.S. Shahrabadi,
D.A. Simpson, and D.E.Woods. 1991. Pseudomonas
aeruginosa exoenzyme-S is an adhesin.
Infect.Immun. 59:2859-2863.
Baker,
N. R. 1991. The role of exoenzyme-S
in the adherence of Pseudomonas aeruginosa.
Pediat. Pulmon. S6: 136-137.
Baker,
N.R., G. Hansson, H. Leffler, G.
Riise, and C. Svanborg-Eden. 1990.Glycosphingolipid
receptors for Pseudomonas aeruginosa.
Infect. Immun.58:2361-2366.
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