University at Buffalo
The Witebsky Center

The Witebsky Center
University at Buffalo
Bacteriology Host-Microbe Interactions Immunology Parasitology Virology
The Witebsky Center The Witebsky Center
Anthony A. Campagnari

Anthony A. Campagnari, Ph.D., Professor
Department of Microbiology & Immunology
/Medicine Biomedical Research Building, 143
Phone: (716) 829-2673
Fax: (716) 829-3889
Email: aac@buffalo.edu

Campagnari

Campagnari Laboratory Research Projects

Our research interests are focused on microbial pathogenesis, particularly on the identification and characterization of virulence factors, adhesins and putative vaccine antigens.  We are currently working on three bacteria associated with human diseases.

Moraxella catarrhalis related research projects.

One major area of focus involves the Gram-negative human pathogen Moraxella catarrhalis.  This bacterium predominantly causes middle ear infections and sinusitis in infants and children, and lower respiratory tract infections in adults. This organism is the third leading cause of otitis media and it is estimated that approximately 50% of children will become colonized by this bacterium in the first six months of life.

One prominent bacterial surface component implicated as a potential virulence factor is the lipooligosaccharide (LOS) molecule. Structural studies show that M. catarrhalis LOS is similar to the LOS of other Gram-negative human mucosal pathogens.  Currently there are no studies that define a role for LOS in pathogenesis nor is there information available regarding the assembly and expression of this major surface glycolipid. The focus of this work is to perform a comprehensive analysis of the genetics and biology of M. catarrhalis LOS.

In addition we are also attempting to identify specific bacterial factors involved in attachment to host tissues.  M. catarrhalis often colonizes the mucosal surfaces in the nasopharynx of young children.  There is a strong correlation between colonization and subsequent development of otitis media.  We have now demonstrated that M. catarrhalis express peritrichious type-IV pili.  Our studies indicate pilus production by this bacterium is iron-responsive and Fur-regulated.  Additional studies will focus on elucidating the prevalence and role of type IV pili in the pathogenesis and host response of M. catarrhalis infections.  We have also recently identified a region of the M. catarrhalis chromosome that has homology to other known filamentous hemagglutinins (FHA).  These large surface proteins have been shown to be important adherence factors particularly in Bordetella pertussis. We are currently characterizing this region and we are beginning studies designed to determine the function of this FHA homologue. 

A second major focus of our research involved the sexually transmitted bacterium, Haemophilus ducreyi.  This is a Gram-negative human pathogen that causes chancroid, an ulcerative STD that is prominent in many third world countries in Africa and Asia.  Infection with H. ducreyi has been shown to be a cofactor in the heterosexual transmission of HIV.

Haemophilus ducreyi related research projects.

We have identified two outer membrane proteins, termed OmpP2a and OmpP2b, which have homology to the major porin of H. influenzae OMP P2.  Porins have been shown to be essential bacterial proteins with multiple functions.  The genes that code for these proteins have been cloned and sequenced.  Subsequent studies have demonstrated that the putative porins are differentially expressed by various clinical isolates of H. ducreyi. The overall goal of this project is to determine the role of these putative porins in the pathogenesis of H. ducreyi infections.

We have recently identified a type 1 fimbria operon in H. ducreyi 35000HP.  The gene encoding the major fimbrial filament subunit has been cloned and a fimA-deficient has been constructed.  Analysis of this mutant strain will yield important insight into the role of fimbriae in H. ducreyi pathogenesis, particularly as it pertains to colonization of the host tissues.

The third emphasis of our work with H. ducreyi involves microarray analysis specifically analyzing gene expression under varying conditions.  The entire chromosome of H. ducreyi strain 35000HP has been sequenced and annotated and a 50mer oligonucleotide array has been developed.  We have performed a preliminary study analyzing gene expression at various time points through out a standard growth curve to demonstrate the effectiveness of the array and also establish baseline levels as a guide for future studies.                  

Acinetobacter baumannii related research projects.

A. baumannii is a Gram-negative pathogen, that is largely associated with nosocomial infections in susceptible populations.  These usually involve post-operative individuals requiring ventilator assisted breathing systems.  The organisms isolated from these patients often exhibit a high degree of antibiotic resistance.  Recently, the military has seen an increased prevalence of multi-drug resistant Acinetobacter-infections in wounded soldiers returning from the Iraq and Afghanistan regions creating interest in studying this under-characterized pathogen.

The biosynthesis and expression of the lipopolysaccharide (LPS) molecule of A. baumannii is a new research focus of our laboratory. LPS is a common constituent of the outer membrane of Gram-negative bacteria and studies are underway to define the role of LPS in the pathogenesis in A. baumannii infections.  Using random transposon mutagenesis, we have identified a gene locus involved in O-antigen biosynthesis.  Studies of defined mutants that can no longer express full-length LPS molecules will yield important insights into the virulence of this opportunistic pathogen.

Our second major focus of research with A. baumannii involves the identification and characterization of conserved, surface-exposed virulence factors.  We have utilized the A. baumannii genome sequence in the NCBI database to select putative targets with homologies to other well-known bacterial components shown to be important in pathogenesis.  These studies will lead to a better understanding of how A. baumannii establishes colonization on human mucosal surfaces.  

Recent Publications:

Luke, N.R., Allen, S., Gibson, B.W. and Campagnari, A.A. 2003. “Identification of a 3-Deoxy-D-Manno-Octulosonic Acid (KDO) Biosynthetic Operon in Moraxella catarrhalis and Analysis of a KdsA-Deficient Isogenic Mutant”. Infect. Immun. 71(11):6426-6434.

Prather, D.T., Bains, M., Hancock, R. E. W., Filiatrault, M.J. and Campagnari, A.A. 2004. “Differential Expression of Porins OmpP2A and OmpP2B of Haemophilus ducreyi”. Infect. Immun. 72(11):6271-6278.

 Furano, K. and Campagnari, A.A. 2004.  “Identification of a Hemin Utilization Protein of Moraxella catarrhalis (HumA).” Infect. Immun. 72(11):6426-6432.

Luke, N.R., Howlett, A.J., Shao, J. and Campagnari, A.A. 2004. “Expression of Type-IV Pili by Moraxella catarrhalis is Essential for Natural Competence and Effected by Iron-Limitation.” Infect. Immun. 72(11):6262-6270.

Furano, K., Luke, N.R., Howlett, A.J. and Campagnari, A.A..  2005. Identification of a Conserved Moraxella catarrhalis Hemoglobin Utilization Protein (MhuA). Microbiology,151(pt. 4):1151-1158.

Characterization of a Cluster of Three Glycosyltransferase Enzymes Essential for Moraxella catarrhalis Lipooligosaccharide (LOS) Assembly.  Journal of Bacteriology, 187:2939-2947.

 Edwards, K.J., Schwingel, J.M., Datta, A.K. and Campagnari, A.A. 2005. Multiplex PCR assay that identifies the major lipooligosaccharide serotype expressed by Moraxella catarrhalis clinical isolates. J Clin Microbiol. 43:6139-6143.

 Janowicz D, Luke N.R., Fortney K.R., Katz B.P., Campagnari A.A,. and Spinola S.M.  2006. Expression of OmpP2A and OmpP2B is not required for pustule formation by Haemophilus ducreyi in human volunteers. Microb Pathog. 40 (3):110-115.

 Plamondon, P., Luke, N.R. and Campagnari, A.A. 2007. Identification of a Novel Two Partner Secretion System for Moraxella catarrhalis. Infect. Immun. 75: 2929-2936.

Nicole R. Luke, N.R., Jurcisek, J., Bakaletz, L.O., and Campagnari, A.A. 2007. Contribution of Moraxella catarrhalis Type-IV Pili to Nasopharyngeal Colonization and Biofilm Formation. Infect. Immun. 75: 5559-5564.

Loehfelm, T.F., Luke, N.R. and Campagnari, A.A. 2008. Identification and Characterization of an Acinetobacter baumannii Biofilm-Associated Protein. Journal of Bacteriology, 190: 1036-1044.

Schwingel, J.M., St. Michael, F., Cox, A.D., Masoud, H., Richards, J.C. and Campagnari, A.A. 2008. Identification and Characterization of a Unique Glycosyltransferase Involved in the Assembly of the Inner Core of Moraxella catarrhalis Lipooligosaccharides.  Glycobiology, 18: 447-455.

Russo, T.R., Beanan, J.M., Olson, R., MacDonald, U., Luke, N.R., Gill, S.R. and Campagnari, A.A. 2008. Rat Pneumonia and Soft-Tissue Infection Models for the Study of Acinetobacter baumannii Biology. Infect. Immun. 76:3577-3586.

Adams, M.D., Goglin, K., Molyneaux, N., Hujer, K.M., Lavender, H., Jamison, J.J., Macdonald, I.J., Martin, K.M., Russo, T., Campagnari, A.A., Hujer, A.M., Bonomo, RA and Gill, S.R. 2008. Comparative genome sequence analysis of multidrug resistant Acinetobacter baumannii. J Bacteriol. 190: 8053-64.

 Davie, J.J. and Campagnari, A.A. 2009. Comparative proteomic analysis of the Haemophilus ducreyi porin-deficient mutant  35000HP::P2AB. Journal of Bacteriology 191(7):2144-52, 2009 Apr.

Luke, N. R.,  S. L. Sauberan, T. A. Russo, J. M. Beanan, R. Olson, T. W. Loehfelm, A. D. Cox, F. St.   Michael, E. V. Vinogradov, and A. A. Campagnari2010. Identification and Characterization of a Glycosyltransferase Involved in Acinetobacter baumannii Lipopolysaccharide Core Biosynthesis. Infect. Immun. 78(5):2017-23. PMID: 20194587.

Russo, T. A., N. R, Luke, J. M. Beanan, R. Olson, S. L. Sauberan, U. MacDonald, L.W. Shultz, T. Umland and A.A. Campagnari. 2010. The K1 capsular polysaccharide of Acinetobacter baumannii strain 307-0294 is a major virulence factor. Infect Immun., 78:993-4000.

 

 


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