B.S., (Honors), University of Dhaka
M.S., University of Dhaka
PhD, Osaka University
Lyme disease, caused by Borrelia burgdorferi, is the most prevalent tick-borne disease placing an increasing burden on public health. Lyme disease is bad—the illness is highly debilitating, and the patients can be bed-ridden and dysfunctional for long periods of time. In addition to Borrelia burgdorferi, spirochetes cause several major diseases in humans such as syphilis, leptospirosis, and periodontitis. These diseases pose significant public health problems throughout the world.
Borrelia burgdorferi can invade almost any tissue and survive and cause disease in the host for years, and thus serve as an excellent model for the study of persistent, invasive pathogens.
Spirochetes periplasmic flagella and motility are fundamentally different from other bacteria but remains poorly understood. Furthermore, the cyclic-di-GMP-mediated regulatory mechanisms involving Borrelia burgdorferi physiology and pathogenesis remains elusive. We use functional genomics, genetics, mouse and tick-mouse models of Lyme disease to study the bacterial virulence mechanisms with special emphasis on the cyclic-di-GMP signaling system, regulatory mechanisms the spirochete uses to control bacterial migration within and between the hosts, and regulation and biosynthesis of periplasmic flagella.
Pathogenic spirochetes are becoming antibiotic-resistant, however, the mechanisms involved are poorly understood. Thus, there is a need to better understand bacterial virulence mechanisms and develop alternative targets for anti-bacterial agents. Our long-term goals are to develop small molecule pharmacological agents to prevent bacterial transmission and therefore, the Lyme disease. Notably,our data indicate that the periplasmic flagella are essential for spirochete motility, which in turn is required for host infection and bacterial transmission. Consequently, these studies can lead to applications in structure-based drug design to disrupt the assembly of the periplasmic flagella, therefore blocking bacterial dissemination and preventing the spread of spirochetal diseases. Alternatively, a pharmacological agent that block a unique spirochetal signaling system can be developed to prevent the spirochete’s transmission and therefore, the disease.
Moon KH, Zhao X, Manne A, Wang J, Yu Z, Liu J, Motaleb MA. Spirochetes flagellar collar protein FlbB has astounding effects in orientation of periplasmic flagella, bacterial shape, motility, and assembly of motors in Borrelia burgdorferi. Molecular Microbiology. 102(2): 336-348. 2016. PMID: 27416872. Journal Cover illustration.
EA, Sekar P, Xu H, Moon KH, Manne A, Wooten RM, Motaleb MA. The Borrelia
burgdorferi CheY3 response
regulator is essential for chemotaxis and completion of its natural infection
Cell Microbiology. ePub May 20,
2016. PMID: 27206578.