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August 2008

Disease Investigation Leads Researchers to Possible New Mycobacterium

Dr. John SpencerIn 2007, a man showed up in a Phoenix health clinic covered with lesions and experiencing sensory loss in his feet. His doctors were mystified as to whether his condition might be caused by a bacterial infection, an autoimmune disease, or a type of cancer. His tissues began to break down, his organs began to fail and, after two weeks in the intensive care unit, the man died. His doctors suspected the man, who was originally from Mexico, died of complications from an aggressive, and often fatal, rare form of leprosy called diffuse lepromatous leprosy with Lucio’s phenomenon.

“We received serum and biopsy specimens from a clinician at the clinic who wanted confirmation of their suspicions of leprosy,” said Dr. John Spencer, an Assistant Professor in the Department of Microbiology, Immunology and Pathology and researcher with the Mycobacteria Research Laboratories. “Through serologic antigen recognition profiling and sequencing analysis of the DNA from this isolate at CSU and by Dr. Xiang Han, Head of the Diagnostic Laboratory at the M.D. Anderson Cancer Center in Houston, it was determined that this mycobacterium, although not cultivatable and bearing close sequence homologies with a number of  M. leprae genes, showed a 2.1% difference with the 16S ribosomal gene, indicating a possible difference in species. It was a mycobacterium, but it wasn’t M. leprae.”

Mexican researchers Lucio and Alvarado first described the pathology and symptoms of  this necrotizing disease found primarily in the Jalisco, Sinaloa and Michoacan provinces In Mexico  in 1852. The disease largely went unnoticed by outside scientists for more than 150 years, though rarely similar cases appeared in other parts of the world. When more than a dozen genes were sequenced last year, none of these sequences matched up to the any of the 110 known mycobacterial species but they were most closely related to M. leprae. Though not officially approved yet, Dr. Han named the new species Mycobacterium lepromatosis, and the paper written about the discovery by Dr. Han with contributions from the Mycobacteria Research Laboratories at CSU was recently accepted by the American Journal of Clinical Pathology, and will likely be published in September.

While gratifying and exciting, the story for Dr. Spencer doesn’t end there. This summer, thanks in part to a small grant funded through the Office of International Programs, he and three students traveled to the provinces of Jalisco and Sinaloa to share their findings. Dr. Spencer; Tammy Lutrell, a PhD student in MIP; Brittny Acres, a Research Associate in the lab who graduated with a bachelor’s in microbiology last year; and Anna Kellund, a student in the Hughes Undergraduate Research Scholars (HURS) Program; met with clinicians and leprosy researchers in the cities of Guadalajara and Culiacan.

Scarring in the skin on a leg of a patient with possible Lucio's leprosy“We were hosted by Dra. Mary Fafutis Morris, a leprosy researcher at the University of Guadalajara, who arranged for us to visit the dermatological clinics at both sites where I gave my presentation,” said Dr. Spencer.  “We saw patients at the clinic in Culiacan and Tammy, a former diabetic ulcer wound care specialist at a clinic in Wyoming, jumped in and spoke with the clinicians about the patients in Spanish.

“They told us about the things they wished they had to better treat patients, simple things like monofilament test devices (to measure sensory loss), a Doppler device (to measure whether the circulation is good or not in the affected limbs or feet), skin temperature measuring  devices (to measure if the skin is too cool, indicating ischemia or circulatory problems), and other simple skin care materials. Tammy is currently working with partners she knows to assemble a care package with needed supplies that we will ship to the clinics in Mexico to help them care for their leprosy patients.”

Dr. Spencer said there also was interest in trying to locate more archived tissue samples of Lucio's or locate new patients so that he might get a fresh biopsy specimen to send to the National Hansen's Disease Program at Louisiana State University to see if the researchers can get the mycobacterium to grow in animal models used for M. leprae (leprosy also is known as Hansen’s disease). Dr. Ric Slayden, also with MIP, is assisting on the DNA microarray comparison of the new bacterium with M. leprae, and the researchers continue to add sequences to the database, currently more than 23,000 bp total. In addition, Dr. Spencer has been invited to speak on the new mybacterium at the Many Host of Mycobacteria II symposium being held in Gettysburg, Penn., Sept. 15-16.