Research in Action: Dr. Carolina Mehaffy

Research in Action

12 Jan 2017

Probing the biological secrets of a clever adversary

Wearing a protective gown, mask, respirator and gloves, Dr. Carolina Mehaffy is staring an old enemy in the face. The petri dish in front of her is teeming with bacteria that cause tuberculosis (TB), still one of the most common infectious diseases worldwide.

Today, Mehaffy is focusing in on a particularly troubling type of TB bacteria: the kind that are resistant to the two main anti-TB drugs, isoniazid and rifampin. Multidrug-resistant tuberculosis is a global public health problem.

“While incidence and death rates for tuberculosis are declining worldwide, cases of multidrug-resistant tuberculosis are actually going up every year in many countries,” says Mehaffy, a scientist at Public Health Ontario.

In 2012, there were an estimated 450,000 new cases of multidrug-resistant TB (MDR-TB) in the world, according to the World Health Organization. That’s roughly five per cent of all new TB cases.

In Canada, where TB rates are low, MDR-TB is present. Figures from the Public Health Agency of Canada show that in 2012, nine cases of MDR-TB were recorded, out of a total of 1,404 new laboratory-confirmed TB cases. Ontario has about 60 per cent of all MDR-TB cases, most of which occur in foreign-born individuals.

But Mehaffy warns against any complacency when it comes to this clever disease. TB can become resistant when medication isn’t administered or taken properly, or is stopped too soon. Drug-resistant TB can also spread directly from person to person.

MDR-TB is difficult and costly to treat. Drugs must be taken daily for up to two years, and can cause serious side effects. Patients may need to be isolated for long periods of time. And there’s a high mortality rate.

As a microbiologist, Mehaffy hopes to outsmart MDR-TB by learning its tricks. She’s zeroing in on the basic biology of the bacteria to understand how it evades powerful drugs.

Scientists already know there are genetic mutations in drug-resistant TB. But Mehaffy has found resistant strains that don’t have those mutations. So what’s going on?

She’s searching the DNA of resistant bacteria for other explanations. Some answers may lie in features of the bacterium’s cell wall, or in proteins that pump out drugs.

In a recently published study that grew out of her postdoctoral research, Mehaffy identified a particular set of lipids (molecules) in the cell wall of resistant bacteria. She believes these lipids may make the wall more impermeable to drugs.

Mehaffy is excited about discoveries like these. They could lead to better detection methods and novel therapies. “If we could develop a treatment that targets these kinds of cell responses, it could be used in addition to current drugs to enhance therapy,” she says.

Mehaffy’s interest in TB was sparked at the age of 23 when she attended a lecture in her native Colombia. The speaker was Dr. Patrick Brennan, a renowned U.S. microbiologist and expert on TB. She was captivated by his talk.

“Afterwards, I had the opportunity to talk with him about some ideas I had,” she recalls. Soon, Mehaffy was the recipient of a World Health Organization grant for young scientists. It helped her in her early work at Colorado State University, a major centre for TB research.

In 2012, Mehaffy leaped at a chance to join PHO, where she does research with application to both the clinical laboratory and a more basic level. She is also an assistant professor of laboratory medicine and pathobiology at the University of Toronto. Though fascinated by her MDR-TB research, Mehaffy is also looking at TB in high-risk communities. There’s a pilot study underway with PHO medical microbiologist Dr. Frances Jamieson, focusing on Toronto’s homeless and under-housed population. The researchers want to know if there are genetic factors in people that may increase the likelihood they will become sick with TB.

“We already know that some people, like those with HIV and other conditions that suppress the immune system, have a higher risk of developing active TB. But there may be genetic factors that make some people more susceptible—as well as factors relating to the bacteria itself, and to the environment,” explains Jamieson. 

Public Health Ontario operates the largest tuberculosis and mycobacteriology laboratory in North America, processing over 60,000 specimens each year. It provides almost 95 per cent of the diagnostic testing and all the reference testing for Ontario. As well, PHO connects with a wide range of partners and clients, from health care providers and institutions, public health units, the broader laboratory sector, academia, and municipal, provincial, federal and international governments. This provides a rich and substantial source of biological specimens and organisms. The volume of tests and range of relationships foster an environment of creativity and collaboration in the pursuit of solutions to address the challenges of tuberculosis elimination. 

Selected publications:

  1. Bisson GP, Mehaffy C, Broeckling C, Prenni J, Rifat D, Lun DS, Burgos M, Weissman D, Karakousis PC, Dobos K. Upregulation of the phthiocerol dimycocerosate biosynthetic pathway by rifampin-resistant, rpoB mutant Mycobacterium tuberculosis. J Bacteriol. 2012;194(23):6441-52.
  2. Mehaffy MC, Kruh-Garcia NA, Dobos KM. Prospective on Mycobacterium tuberculosis proteomics. J Proteome Res. 2012;11(1):17-25.
  3. Mehaffy C, Hess A, Prenni JE, Mathema B, Kreiswirth B, Dobos KM. Descriptive proteomic analysis shows protein variability between closely related clinical isolates of Mycobacterium tuberculosis. Proteomics. 2010;10(10):1966-84.
  4. Mehaffy C, Brennan PJ, Dobos KM. Proteomics studies and antigen discovery. In: The art and science of tuberculosis vaccine development. Nor MN, Acosta A, Sarmiento ME, editors. Selangor Darul Ehsan, Malaysia: Oxford University Press; 2010. p. 47-58.
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Updated 12 Jan 2017