Molecular Sciences Faculty Directory
Robert Belland, Ph.D.
Associate Professor
858 Madison Ave.
Room 801
Memphis, TN 38163
Email: rbelland@utmem.edu
Phone: 901-448-8544
Fax: 901-448-7360
Research Interests
My research effort is directed at understanding the pathogenic characteristics of Chlamydia trachomatis and C. pneumoniae that contribute to chronic human diseases such as trachoma, infertility, reactive arthritis and atherosclerosis. These disease syndromes generally follow less severe acute infections. The development of long-term, persistent disease states is complex and it is not clear whether disease progression is due to specific characteristics of the host or pathogen. We have used a functional genomic approach to identify pathogen-specific genotypes and phenotypes associated with chronic diseases. In the future we would like to complement these studies by determining host-susceptibility patterns associated with chronic disease.
Chlamydia pneumoniae and Atherosclerosis
Exposure to C. pneumoniae is extremely common and respiratory infections occur
repeatedly among most people. Strong associations exist between C. pneumoniae
infection and atherosclerosis as demonstrated by (a) sero-epidemiological
studies showing patients with cardiovascular disease have higher titers of
anti-C. pneumoniae antibodies compared with control patients, (b) detection of
the organism within atherosclerotic lesions, but not adjacent normal tissue by
immunohistochemistry, PCR and electron microscopy and by culturing the organism
from lesions (c) demonstrating that C. pneumoniae can either initiate lesion
development or cause exacerbation of lesions in rabbit and mouse animal models,
respectively. The association of this organism with atherosclerosis also has
provided sufficient impetus to conduct a variety of human secondary prevention
antibiotic treatment trials. Results of these studies have been mixed, and thus
far no clear long lasting benefit has emerged from these types of
investigations. Studies of C. pneumoniae pathogenesis have shown that the
organism can infect many cell types associated with both respiratory and
cardiovascular sites including lung epithelium and resident alveolar
macrophages, circulating monocytes, arterial smooth muscle cells and vascular
endothelium. Infected cells have been shown to exhibit characteristics
associated with the development of cardiovascular disease (e.g. secretion of
proinflammatory cytokines and procoagulants by infected endothelial cells and
foam cell formation by infected macrophages). More detailed analysis of C.
pneumoniae pathogenesis has been aided by the availability of genomic sequence
information. Genomic and proteomic analyses of C. pneumonie infections in
relevant cell types will help define the pathogenic potential of the organism in
both respiratory and cardiovascular disease. C. pneumoniae, like all chlamydiae,
is an obligate intracellular prokaryotic pathogen. Unlike C. trachomatis, the
other major human chlamydial pathogen, which exhibits an in vivo tropism for
mucosal epithelial cells, C. pneumoniae can infect and survive in a wider array
of host cell types, including lung epithelium, resident macrophages (alveolar
and monocyte derived), circulating monocytes, arterial smooth muscle cells and
vascular endothelium. C. pneumoniae can infect and modify the physiology of the
various cell types present in the lung, circulation, and atheroma itself and may
transit from the lung to the atheroma via circulating and. The C. pneumoniae
intracellular developmental cycle resembles that of other chlamydiae in its
general features (Fig.1).
Chlamydiae remain within the confines of the host cell vesicle throughout their
cycle of intracellular development but modify this structure in several ways
during their growth phase. The final stages of chlamydial growth during a
productive infection involve differentiation of RB back to EB. This is
accompanied by lysis of the host cell or direct release of EB. Productive
infections are only one of several possible outcomes of chlamydial interactions
within any given host cell. Chronic chlamydial infections have been recognized
in vivo for decades and physiologic mediators of persistence include
immune-regulated cytokines such as gamma-interferon (IFN-g) and tumor necrosis
factor alpha (TNF-a). These attributes are consistent with involvement of
chronic diseases such as atherosclerosis.
C. pneumoniae has the capacity to initiate and propagate inflammation in ways
that contribute to atherosclerosis. The pathogen likely accesses the vasculature
during local inflammation in a lower respiratory tract infection. The organism
disseminates systemically but exhibits tropism to arterial vasculature. The
pathogen can infect and multiply within all cell types commonly found in the
atheroma, including coronary artery endothelial cells, macrophages, and aortic
artery smooth muscle cells.
One growth characteristic likely to be associated with long-term disease in
cardiovascular tissue is the tendency or ability of the isolate to establish
persistent infections. The application of genomic analyses to clinical isolates
should provide useful information in the development of therapeutic approaches
that target isolates most likely to be associated with CVD and should help in
the development of diagnostic tools that indicate the presence of isolates
associated with the development of CVD.
Figure Legends
Figure 1. The developmental cycle of C. pneumoniae. The normal cycle may be
disrupted by the induction of persistence due to nutritional deprivation,
antibiotic treatment, or growth in specific cell types and the appearance of
large aberrant bacterial forms. Reactivation of the normal developmental cycle
can be seen in many cases when the inducer of persistence is removed.
Figure 2. The polyclonal nature of C. pneumoniae strains causing respiratory
disease can be demonstrated by the presence of distinct mixtures of bacterial
genotypes (as described in Table 1) in strain isolates. Certain genotypes may
exhibit a selective advantage in the ability to disseminate or establish
infection in cardiovascular sites.
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Education
- B.Sc., 1981, University of Victoria (Biochemistry and Microbiology), Victoria, British Columbia, Canada
- Ph.D., 1987, University of Victoria (Biochemistry), Victoria, British Columbia, Canada
