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Our Scientists

Bavesh D. Kana, PhD
International Early Career Scientist / 2012–Present

Scientific Discipline

Genetics, Molecular Biology

Host Institution

University of the Witwatersrand, Johannesburg

Current Position

Dr. Kana is a senior researcher and head of the University of the Witwatersrand node of the Department of Science and Technology/National Research Foundation Center of Excellence for Biomedical TB Research in the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Current Research

Remodeling of the Mycobacterial Cell Wall

Bavesh Kana studies the enzymes that are predicted to be involved in remodeling the mycobacterial cell wall and their contribution to modulation of bacterial growth and reactivation from dormancy. He is specifically interested in the role these enzymes play in determining the complex clinical outcomes that are seen with infection by Mycobacterium tuberculosis, the causative agent of tuberculosis.

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Electron micrograph of mycobacterial cells...

Biography

Growing up in Johannesburg, South Africa, in the 1980s, Bavesh Kana saw workers on his father’s farm unknowingly passing tuberculosis (TB) infection to each other and members of his family. A few workers even died from the dreaded…

Growing up in Johannesburg, South Africa, in the 1980s, Bavesh Kana saw workers on his father’s farm unknowingly passing tuberculosis (TB) infection to each other and members of his family. A few workers even died from the dreaded disease.

Roughly one-third of the world’s population—2 billion people—is infected with TB. But the problem is particularly acute in southern Africa, Kana says. South Africa ranks third among the TB high-burden countries, confirming that many South Africans are infected with the bacteria that cause the disease. The rampant HIV epidemic in the region worsens the situation, since the virus increases susceptibility to TB and coinfection complicates the treatment of both conditions.

Having seen the effects of the disease as a child helped motivate Kana to study science when he got to college. The University of the Witwatersrand in his hometown was the most affordable option for his undergraduate studies, and a logical choice, he says, for a student who came from “humble beginnings.” Fortunately, the university also happened to be home to an outstanding TB research group, so Kana stayed there for his doctoral work. He quickly learned that the scientific advances researchers needed to conquer the disease would not come easily.

“The thing about TB research is that it’s not a field that one goes into lightly,” he says. “The organism is remarkably adapted to its human host, there are multiple disease states, and, in the lab, the bacteria take a month to form colonies on plates. Any investment has to be long term.”

Kana is committed to the challenge. One of the most frustrating aspects of TB infection is the bacterium’s ability to slip into a latent state, lurking in the body without causing symptoms but capable of sickening its host and transmitting to others months or even years later. Furthermore, current drugs do not effectively target dormant infections. Even successful TB treatment can leave a residual population of bacteria in the body that can reactivate later.

Most people infected with TB never develop symptoms and are not contagious, but 10 to 20 percent will develop active disease, depending on their HIV infection status. “We don’t understand the process of reactivation very well,” Kana says. “Something happens in bacterial cells to cause them to shift from dormant to actively growing.”

As a postdoctoral researcher working with Valerie Mizrahi, a former HHMI International Research Scholar at the University of the Witwatersrand (and now an HHMI Senior International Research Scholar at the University of Capetown), and Gilla Kaplan at the University of Medicine and Dentistry of New Jersey, Kana defined a class of enzymes that TB bacteria produce and use to shift from dormant to active, called resuscitation promoting factors (Rpfs). (Mizrahi and Kaplan are advisors to the KwaZulu-Natal Research Institute for Tuberculosis and HIV, a new South African research center funded by HHMI.)

These factors snip peptidoglycan, a layer of the bacterial cell wall that gives it rigidity. Many traditional antibiotics, such as amoxicillin, work by preventing bacteria from manufacturing this critical structural component. But Kana points out the bacterial life cycle also requires that this layer be remodeled after it is produced. “When the cell needs to divide, peptidoglycan remodeling allows for expansion and cell division,” he explains. Researchers know that remodeling of the cell wall is also necessary for some other species of dormant bacteria to reactivate.

Kana believes that Rpfs enable this remodeling by snipping free the molecules that make up peptidoglycan. TB bacteria possess five different Rpf genes, possibly with overlapping functions—making it difficult to tease out their precise roles in infection. Kana and his collaborators laboriously knocked out the five Rpf genes in the bacterium in several possible combinations and tested them in a mouse model of TB infection. Deleting four or all five genes, which should prevent peptidoglycan remodeling, made the TB bacteria very weak.

Kana envisions that a drug that inactivates Rpf enzymes could block reactivation of latent TB, and his research suggests another possible advantage of such drugs. His hypothesis is that deleting Rpfs would block the production of muropeptides, which are shed from the peptidoglycan layer as it expands and, in mice, trigger a strong inflammatory response by the immune system. This reaction leads to the formation of lesions in the lung, where TB bacteria hide out and persist. Kana now plans to investigate the role of Rpfs and muropeptides in human TB infection.

His research group’s findings may even speed diagnosis and treatment for South Africans in the near term. It takes weeks to culture bacteria from a sputum sample to determine a patient’s TB status. Kana’s group would like to speed this process up by using Rpfs and muropeptides. A speedier diagnosis will allow for better patient management and for prescribing the most appropriate drugs in the case of patients who carry drug-resistant TB. “I’m very excited that we might be able to take our findings all the way to the clinic,” he says.

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Education

  • BSc, biochemistry and genetics, University of the Witwatersrand, South Africa
  • BSc Hons, biochemistry, University of the Witwatersrand, South Africa
  • PhD, mycobacteriology, University of the Witwatersrand, South Africa

Awards

  • Friedel Sellschop Research Award
  • South African Medical Research Council Career Development Award