James T. Summersgill, Ph.D.
James T. Summersgill, Ph.D.
Professor of Medicine
Director, Infectious Diseases Laboratory
Division of Infectious Diseases
Department of Medicine
Room 311, Instructional Building
500 South Preston Street
University of Louisville
Louisville, Kentucky 40292
Facsimile (502) 852-1512
Chlamydia pneumoniae is a human respiratory pathogen serving as the etiologic agent in cases of pneumonia, bronchitis and sinisitis. Most humans are exposed to this obligate intracellular bacterium at some point in their lives, perhaps numerous times, as evidenced by increasing antibody titers with age. Recently, data has emerged indicating that a potential sequella following infection with C. pneumoniae may be an increased risk for the development of atherosclerosis and coronary artery disease, likely as a result of systemic spread from the initial site of infection. Numerous techniques have demonstrated the presence of this organism in foam cells of macrophage and smooth muscle cell origin in approximately 70% of athermatous lesions examined, but not in normal arterial tissue. Isolation of viable organisms has been reported on two occasions. In addition, animal models have been developed resulting in the presence of C. pneumoniae in atherosclerotic plaques. Presence in atheromatous tissue, however,does not answer the crucial Question: Is C. pneumoniae merely an "innocent bystander" or does it possess biological features consistent with a significant role for this bacterium in the initiation or exacerbation of atherosclerosis?
We are characterizing the C. pneumoniae altered intracellular life cycle, in vitro, in response to cytokine treatment of the host cell. This altered life cycle may take the form of a "persistent state", similar to that described in detail for C. trachomatis. Induction and regulation of indoleamine-2,3-dioxygenase (IDO) activity in response to cytokine treatment, with resulting tryptophan degradation, will be determined in aortic smooth muscle cells (ASMC). We are using a proteomics approach to study differential expression of C. pneumoniae genes from persistently infected cells. A persistent form of C. pneumoniae in vivo will be necessary for this bacterium to survive in host tissue and potentially evade the host immune response.
- Hogan R, Matthews S, Mukhopadhyay S, Summersgill J & Timms P. Chlamydial Persistence: Beyond the Biphasic Paradigm. Infect. Immun. 72:1843-1855, 2004.
- Uriarte, SM, Molestina RE, Miller RD, Bernabo J, Farinati A, Eiguchi K, Ramirez JA & Summersgill JT. Effect of Fluoroquinonlone Antibiotics on the Migration of Human Phagocytes Through Chlamydia pneumoniae-Infected and Tumor Necrosis Factor alpha-Stimulated Endothelial Cells. Antimicrob. Agents Chemother. 2004.
- Mukhopadhyay S, Sullivan E, Clark A, Miller RD & Summersgill JT. Purification of Chlamydia pneumoniae elementary bodies: A detailed protocol. J. Clin. Microbiol. 2004.
- Mukhopadhyay S, Miller RD & Summersgill JT. Analysis of altered protein expression patterns of Chlamydia pneumoniae by an integrated protoeme-works system. J Proteomics Res. 2004.
- Molestina RE, Klein JB, Miller RD, Pierce WH, Ramirez JA & Summersgill JT. Proteomic anlaysis of differentially expressed Chlamydia pneumoniae genes during persistent infection of HEp-2 cells. Infect. Immun. 70:2976-2981, 2002.
- Uriarte, SM, RE Molestina, RD Miller, J Bernabo, A Farinati, K Eiguchi, JA Ramirez & JT Summersgill. Effect of macrolide antibiotics on human endothelial cells activated by Chlamydia pneumoniae infection and tumor necrosis factor alpha. J. Infect. Dis. 185:1631-1636, 2002.
- Pantoja LG, Molestina RE, Miller RD, Ramirez JA & Summersgill JT. Characterization of Chlamydia pneumoniae persistence in HEp2 cells treated with interferon-gamma. Infect. Immun. 69:7927-7932, 2001.
- Pantoja LG, Molestina RE, Miller RD, Ramirez JA & Summersgill JT. Inhibition of Chlamydia pneumoniae replication in human aortic smooth muscle cells by interferon-gamma-induced indoleamine 2,3-dioxygenase acitivity. Infect. Immun. 68:6478-6481, 2000.
- Molestina RE, Miller RD, Ramirez JA & Summersgill JT. Infection of endothelial cells with Chlamydia pneumoniae stimulates transendothelial migration of neutrophils and monocytes. Infect. Immun., 67:1323-1330, 1999
- Molestina RE, Miller RD, Lentsch AB, Ramirez JA & Summersgill JT. Requirement of NF-KB for MCP-1 mRNA in Chlamydia pneumoniae-Infected Endothelial Cells. Infect. Immun., 68:4282-4288. 2000.
- Summersgill JT, Molestina RE, Miller RD & Ramirez JA. Interactions of Chlamydia pneumoniae with human endothelial cells. J. Infect. Dis. , 181(Suppl):S479-482, 2000.
- Molestina RE, Miller RD, Ramirez JA & Summersgill JT. 1998. Characterization of a strain of Chlamydia pneumoniae isolated from a coronary atheroma by analysis of the omp1 gene and biological activity in human endothelial cells. Infect. Immun. 66:1370-1376.
- Mehta SJ, Miller RD, Ramirez JA & Summersgill JT. 1998. Inhibition of Chlamydia pneumoniae replication in HEp-2 cells: role of tryptophan catabolism. J. Infect. Dis. 177:1326-1331.
- Ramirez JA, Ahkee S, Summersgill JT, Ganzel BL, Ogden LL, Quinn TC, Gaydos CA, Bobo LL, Hammerschlag MR, Roblin PM, LeBar W, Grayston JT, Kuo CC, Campbell LA, Patton DL, Dean D & Schachter J. 1996. Isolation of Chlamydia pneumoniae from the coronary artery of a patient with coronary atherosclerosis. Ann. Intern. Med. 125:979-982 .
- Emre U, Bernius M, Roblin P, Gaerlan PF, Summersgill JT, Steiner P, Schachter J & Hammerschlag MR. 1996. Chlamydia pneumoniae infection in patients with cystic fibrosis. Clin. Infect. Dis. 22:819-823, 1996.
- Gaydos CA, Summersgill JT, Sahney NN, Ramirez JA & Quinn TC. 1996. Replication of Chlamydia pneumoniae in vitro in human macrophages, endothelial cells and aortic artery smooth muscle cells. Infect. Immun. 64:1614-1620.
- Summersgill, JT, Gaydos, CA, Sahney, NN, Quinn, TC & Ramirez, JA. 1995. Inhibition of Chlamydia pneumoniae growth in Hep2 cells pretreated with interferon gamma and tumor necrosis factor alpha. Infect. Immun. 63:2801-2803.