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NAME: Dominique
M. Galli, Ph.D.
PHONE: (317)
278-1936
FAX: (317) 278-1411
E-MAIL: dgalli@iupui.edu
OFFICE ADDRESS:
Indiana University School of
Dentistry
Department of Oral Biology
1121 West Michigan Street, Room 261
Indianapolis, Indiana 46202
POSITION/TITLE:
Associate Professor
Department of Oral Biology
Faculty Fellow
Office of the Executive Vice Chancellor and Dean of Faculties
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EDUCATION:
M.S. in Biology, Ludwig Maximiliams-Universität, Munich, Germany
PhD. in Microbiology, Ludwig Maximiliams-Universität, Munich, Germany
Postdoctoral Fellowship, University of Texas Health Science Center, San Antonio, TX
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RESEARCH INTERESTS
Aggregatibacter (formerly Actinobcacillus)
actinomycetemcomitans (Aa) is a Gram-negative facultative,
capnophylic, coccobacillus found in the oral cavities of healthy and
periodontally affected individuals. The organism has been implicated as the
causative agent of aggressive periodontitis as well as other types of human
infections. Aa is also a member of a clinically important group of
bacteria, the HACEK group that is responsible for 3-10% of cases of infective
endocarditis. For a long time a thorough study of Aa virulence traits was
hampered due to the lack of an appropriate genetic system. In recent years, the
core of our research has focused on the use of plasmids and other mobile genetic
elements to develop molecular biological and genetic tools that will allow for
an investigation of the functionality and regulation of putative Aa
virulence traits. The use of these genetic tools has been crucial in the
initiation of the following three projects.
1. Aa-neutrophil interaction
It has been widely accepted that periodontal pathogens have
the ability to evade or inhibit the host immune system. For Aa to be
established in the host it must protect itself from the numerous host defenses,
starting with resistance to phagocytosis and/or killing by neutrophils. In order
to elucidate Aa-neutrophil interactions we have initiated a comprehensive
study including Aa strains, which differ in their serotype, their ability
to express leukotoxin, and their ability to express surface fimbriae. Bridging
the gap between the disciplines of microbiology and cell biology, data obtained
have provided new insights as to how Aa may resist killing by neutrophils.
2. Characterization of biofilms formed by Aa
The etiology of periodontal disease is complex and involves
bacteria that adhere to and colonize the mostly anaerobic environment in the
subgingival pocket to form a biofilm. Fresh clinical isolates of Aa
express fimbriae, are self-aggregating and form tenacious biofilms on surfaces,
such as glass, plastic and saliva-coated hydroxyapatite. A phenotypically
distinct variant no longer expresses these fimbriae and, according to published
literature, has lost the ability to self-aggregate. Currently, we are
characterizing biofilms formed by Aa under different environmental
conditions by use of 2-photon laser scanning confocal microscopy and
computational image analysis. Our preliminary data indicate that loss of
fimbriae does not prevent biofilm formation, although there are noticeable
differences in the structure of biofilms when comparing self-aggregating and
non-aggregating variants of Aa. Secondly, Aa can form biofilms
under aerobic and anaerobic conditions. Oxygen-related variations in biofilm
formation may play a role in the adaptation of Aa to different host
environments (periodontal pocket vs. heart tissue).
3. Conjugative transfer in mixed biofilms
Antibiotic resistance has been increasingly described among
bacterial species including oral microorganisms. Despite the magnitude of this
problem there is still a critical gap in the knowledge base that centers on the
frequency and mechanism of spread of resistance genes in microbial biofilms.
Resistance genes are often carried on mobile genetic elements capable of
interspecies transmission. Our goal is to monitor the potential, the extent, and
the dynamics of conjugative gene transfer in biofilms in situ. We are
currently attempting to design a simple broad-host-range genetic tool based on a
DNA inversion system that we discovered on a native Aa plasmid. The new
tool will allow for the non-intrusive visual tracking of mobile genetic elements
in multispecies biofilms. The availability of this new genetic tool will
facilitate future assessment on the true level of conjugative transfer in
situ in any biofilms of clinical significance.
SELECTED PUBLICATIONS
Galli, D.M., and M.A. Menke. Characterization of the
transposition mode of insertion element IS1216V in a Gram-negative
host. (in preparation)
Gustavsson, A., and D.M. Galli. Oxygen-related variation
in biofilm formation of fimbriated and non-fimbriated Aggregatibacter
actinomycetemcomitans. (in preparation)
Barry, M., Galli, D.M., Hakim, F.F., Holyfield, L.J.,
O’Donnell, J.A., Robbins, M.R., and R.S. Wilder. Dental education's role in
preparing students for an interprofessional health care team. (in
preparation)
Chen, Z., Galli, D. M., Pierce, M.R., and R.L. Gregory.
Involvement of quorum sensing in Streptococcus mutans antigen I/II
regulation. Infect. Immun., submitted.
Chen, J., Pappas, D., and D.M. Galli. Functional
and mutational analysis of the pVT745-specific oriT. J Bacteriol,
submitted, currently being revised.
Galli, D.M., and J. Chen. 2006. Entry exclusion activity
on conjugative plasmid pVT745. Plasmid, 55(2):158-163.
Permpanich, P., Kowolik, M., and D.M. Galli. 2006.
Resistance of fluorescent-labeled Actinobacillus actinomycetemcomitans
strains to phagocytosis and killing by human neutrophils Cell. Microbiol,
8(1):72-84.
Chen, J., LeBlanc, D. J., and D. M. Galli. 2002. DNA
inversion on conjugative plasmid pVT745. J. Bacteriol. 184:5926-5934.
Galli, D. M., Kerr, M. S., Fair, A. D., Permpanich, P.,
and D. J. LeBlanc. 2002. Parameters associated with cloning in
Actinobacillus actinomycetemcomitans. Plasmid 47: 138-147.
Galli, D.M., Chen, J., Novak, K.F., and LeBlanc, D.J.
2001. Nucleotide sequence and analysis of conjugative plasmid pVT745. J.
Bacteriol. 183:1585-1594.
Galli, D.M., and LeBlanc, D.J. 1997. Identification of a
maintenance system on rolling circle replicating plasmid pVT736-1. Mol.
Microbiol. 25:649-659.
Galli, D.M., Polan-Curtain, J.L., and LeBlanc, D.J. 1996.
Structural and segregational stability of various replicons in
Actinobacillus actinomycetemcomitans. Plasmid 36:42-48.
Galli, D.M., and LeBlanc, D.J. 1995. Transcriptional
analysis of rolling circle replicating plasmid pVT736-1: Evidence for
replication control by antisense RNA. J. Bacteriol. 177:4474-4480.
Galli, D.M. and LeBlanc, D.J. 1994. Characterization of
pVT736-1, a rolling circle DNA plasmid from the gram-negative bacterium
Actinobacillus actinomycetemcomitans. Plasmid 31:148-157.