Vaccines and diagnostics development for bacterial infectious diseases
Functional genomics of bacteria using single-cell technology
Pathogenesis research of Pseudomonas aeruginosa, Burkholderia species, Mycobacterium leprae, and Leptospira species
The Hoang Lab currently has several areas of infectious disease research interests, focusing on the genetics and pathophysiology of i) B. pseudomallei, ii) P. aeruginosa, and M. leprae.
i) B. pseudomallei is a CDC Tier 1 agent, causing a disease called melioidosis throughout the tropical regions worldwide, mainly in Southeast Asia and Northern Australia. The disease resembles and can be misdiagnosed for many other bacterial diseases, but the mortality rates of infected patients can be as high as 50-90% if untreated. This bacterium can often be isolated from the water and soil of rice fields (panel A) and other environments throughout tropical regions. Aerosols inhalation containing this species is the most common cause of infection. Hence, precautions to prevent inhalation from the environment and, especially, in the laboratory are necessary (panels B and C).
There is currently no vaccine for melioidosis. The current research focuses on the molecular pathogenesis of B. pseudomallei during its infection of host cells at defined infectious stage (vesicle, cytoplasm, and membrane protrusion; panels D-F). Through our pioneering of single-cell technology and functional genomic studies, we have identified several potential vaccine candidates that we are currently testing in our vaccine formulation.
The lab has also pioneered, successfully tested, and published several molecular genetic tools, aiding molecular genetic studies in B. pseudomallei and other Burkholderia species. The ease of genetic manipulations of B. pseudomallei using these tools will expand research that will contribute to molecular genetics, pathogenesis, and bacteria-host interaction studies - crucial for the discovery of novel vaccines, therapeutics, and diagnostic targets.
A B C
ii) P. aeruginosa is an opportunistic pathogen of plants, animals, and humans. P. aeruginosa is a major bacterium causing in Cystic Fibrosis (CF) lung infection in CF patients, where the bacterium causes life-long infection through biofilm formation. Our focus is to understand the nutrient source affording bacterial replication (A, B, and C) and biofilm formation (D and E) in the lung of CF patients. Knowledge of the pathophysiology of P. aeruginosa will lead to innovative approaches for improved treatment, extending the lives of CF patients who suffer from debilitating and fatal chronic lung infections.
Lung surfactant components (90% lipids and 10% proteins), especially lipids, are absolutely essential for normal pulmonary function. Of the 90% lipids in lung surfactant, 80% is phosphatidylcholine (PC). The lipid component of lung surfactant (i.e., PC) is readily metabolized by P. aeruginosa in vitro. By performing functional genomics of P. aeruginosa directly from CF sputum, we discovered that this bacterium expressed all the genes necessary to degrade lung surfactant as a nutrient source.
P. aeruginosa nutrient acquisition in CF lungs
Spatial gene-expression in the P. aeruginosa biofilm
iii) Leprosy or Hansen’s Disease, caused by M. leprae, is historically significant in Hawaii and is still relevant today with new cases each year. The World Health Organization reported 216,108 new patients in 2016. For thousands of years that leprosy has been in existence, we still know little of what the bacterium does in the human body because it cannot be grown and easily studied. There are only two known places in nature where the bacterium grows, the human body and the footpad of the 9-banded armadillo.
Through collaboration with colleagues in Vietnam, we have extended our single-cell technology to perform functional genomics of M. leprae isolated directly from leprosy patients, to better understand how this bacterium operates in the human body. M. leprae single-cells were isolated directly from skin samples of infected leprosy patients for functional genomics studies. The functional genomics data has also led to potential early diagnostics to treat infected patients, preventing and before the occurrence of the more obvious signs and symptoms associated with the significant social stigma of this physical and psychological disease. We have found potential candidates that may serve as early diagnostics specific for this disease and is the focus of our current research.