Researchers at The University of Arizona College of Medicine's Department of Immunobiology have discovered that the agent that causes tuberculosis (TB), Mycobacterium tuberculosis, produces a new type of virulence factor called Mycobacterium Tuberculosis Pili (MTP). Their findings suggest that MTP could be a promising, new TB-vaccine candidate.
The study, "Mycobacterium tuberculosis produces pili during human infection," published in the Proceedings of the National Academy of Sciences, Volume 104, March 5-9, 2007, could spur further scientific investigations on TB, which is the No. 1 cause of bacterial infectious disease in the world today. Worldwide, 3 million people die each year from tuberculosis and an estimated 1.2 billion are infected with the bacteria.
Virulence factors, such as MTP, are essential for causing disease in the host. Pili, also called fimbriae, are hair-like adhesive structures that facilitate the initial attachment and subsequent colonization of bacteria on human cells during bacterial infections.
Many other bacteria that cause human disease produce similar adhesive factors known as pili or fimbriae that play a critical role in allowing infections to develop in the patient. This is the first report of pili being produced by M. tuberculosis.
"Tuberculosis remains the most devastating bacterial cause of human mortality today. Despite improved diagnosis, surveillance, and treatment regimens, the incidence of TB increases annually. The ability to combat this deadly pathogen hinges on the dissection and understanding of the mechanisms of pathogenesis for M. tuberculosis," writes Christopher Alteri, PhD, a former UA graduate student who is principal author on this study.
This important work was part of his dissertation research at the UA under the direction of Richard L. Friedman, PhD, professor of immunobiology. Dr. Alteri now is a postdoctoral fellow at the University of Michigan Medical School. Jorge A. Girón, PhD, UA assistant professor of immunobiology, and Juan Xicohténcatal, PhD, his postdoctoral fellow, collaborated on this study.
If M. tuberculosis pili are important for the bacillus to establish infections in humans, as with other microbes, then MTP could be considered an attractive new TB vaccine candidate, according to the study. Presently, there is a great need to develop more effective immunization strategies against this devastating disease.
Focusing on the pili adhesive factor produced by M. tuberculosis, which may enable the bacillus to colonize and grow within the human host, the UA experiments demonstrated that when the gene for pili is inactivated, the bacteria do not bind as well to host surface cell proteins, said Dr. Friedman. Serum from TB patients was found to have antibodies to MTP, which indicates that the pili are produced by the bacteria during human infection.
While most tuberculosis infections and deaths occur in Africa, Asia and India, the United States has experienced recent outbreaks. "AIDS patients, who do not have intact immune systems, are highly susceptible to TB infection. This is a major reason for the worldwide increase in the incidence of TB. This increase also is associated with poverty, the growing numbers of homeless, alcohol- and drug-abusing populations, as well as with the emergence of multi-drug resistant strains of M. tuberculosis. Such strains constitute a very serious public health problem because they cannot be treated with any of the most commonly used anti-tuberculosis antibiotics, resulting in high mortality and rates of transmission," said Dr. Friedman.
In addition to Drs. Alteri, Friedman, Girón and Xicohténcatl, researchers who participated in this study are Sonja Hess, National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH), and Guillermo Caballero-Olín, Instituto Mexicano del Seguro Social, Mexico.
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