Dec. 28, 2011

Why it is Hard to Treat Tuberculosis

by Mariel Emrich

Click to enlarge images

By Mariel Emrich, Columbia Grammar and Preparatory School

Pictured here are two cells that have grown asymmetrically, each with a green pole (non-growing and made up of old, stained cell wall) and a blue pole (growing and made up of new cell wall). (Credit: Image courtesy of Harvard School of Public Health)

Tuberculosis (TB) is caused by the bacteria Mycobacterium tuberculosis, which you can get exposed to by breathing in air droplets from a cough or sneeze of an infected person. Infants, the elderly, and people with weakened immune systems have a higher risk of getting TB. Risks of contracting TB increase if you are in frequent contact with people who have TB, have poor nutrition, or live in crowded or unsanitary living conditions. In the United States, there are about 10 cases of TB per 100,000 people.

Symptoms of TB include coughing, excessive sweating, fatigue, fever, and unintentional weight loss. Tests a doctor may take to see if a patient has TB include bronchoscopy, chest CT scan, and chest x-ray. If these tests show the patient has clubbing of the fingers or toes (mostly in people with advanced disease), enlarged or tender lymph nodes in neck, fluid around lung, or unusual breath sounds (crackles), they most likely have TB.

TB is a difficult disease to treat. People are prescribed a combination of many antibiotics to be taken daily for 6 to 9 months. This is a schedule that is hard for patients to follow and hard for their nurses and doctors to administer. Even after beginning the appropriate treatment, some of the infectious cells survive for long periods of time.

Scientists at Harvard School of Public Health (HSPH), led Bree Aldridge, Marta Fernandez-Suarez, and senior author Sarah Fortune, assistant professor of immunology and infectious diseases, conducted a study to figure out why some tuberculosis cells are inherently more difficult to treat with antibiotics. These scientists set out to distinguish which cells live and which cells die after treatment and the reasons some cells are more resistant to treatment. Their results were published December 15, 2011 in an advance online edition of Science.

The researchers designed a unique microfluidic chamber in which they grew Mycobacterium smegmatic cells (which behave closely to Mycobacterium tuberculosis cells). The cells' walls were stained with a green fluorescent dye. Next, the cells were grown in a stain-free media. They filmed the cells' growth with a live-cell imaging system. New growth is unlabeled and appears blue, while the old cell wall retains the green dye and appears green.

The researchers predicted that the M. smegmatis cells would divide evenly into similar-sized daughter cells. However, the cells divided into daughter cells of a wide range of sizes. This diversity in the size of daughter cells occurs because M. smegmatis grow in an unusual manner, elongating from one end.

The researchers figured that these different sized daughter cells would be susceptible to different antibiotics. Therefore, they treated each cell with different antibiotic treatments according to their size. Different daughter cells did have different susceptibilities to the treatments.

Learning more about how the bacteria responsible for TB grow gives researchers a better idea of why tuberculosis is such a difficult disease to treat and may lead to better targeted treatments in future.

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Mariel is currently a sophomore at Columbia Grammar and Preparatory School in New York City. She loves learning about science and particularly enjoys genetics, cancer research, radiology, and forensics.

About Mariel Emrich

The views expressed are those of the author and are not necessarily those of Science Friday.

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