Spotting the culprits - new test for TB
MRC News
Scientists at the MRC's Molecular and Cellular Biology Centre have devised a
more sensitive new test to indicate the presence of Mycobacterium tuberculosis
bacilli in tissue. Their research might also help to explain how the bacilli can
persist in humans.
Tuberculosis (TB) is an infectious disease believed to cause an estimated 2
million deaths each year. The incidence of TB in South Africa is about 400 per
100 000 persons and is set to rise because of high TB/HIV co-infection rates.
The disease is caused by Mycobacterium tuberculosis. Usually their presence
is detected by means of the Ziehl-Neelson (ZN) stain, which shows acid
alcohol-fast bacilli. "But some of our patients test negative using the ZN
stain, because they have very low counts of bacilli," explains Dr Gael
Fenhalls, a Specialist Scientist at the MRC's Molecular and Cellular Biology
Centre.
Their new method detects Mycobacterium tuberculosis gene expression in the
human host. This method is very sensitive (it can detect very low levels of gene
expression) and less time-consuming than the ZN stain method. But because it can
detect novel genes being expressed by the bacilli, it can also aid in developing
new drug treatments.
Dr Fenhalls explains: "Patients with active TB harbour these bacilli in
various metabolic states - from actively growing bacilli to those in a state of
persistence. These persistent organisms are resistant to medication and require
at least 6 months of therapy to sterilise. But patients often give up their
treatment because it's so long, and this raises the risk of drug resistance
developing. So it will improve treatment if we can find a drug that can
eradicate persistent organisms and so shorten the duration of therapy."
TB leads to the formation of so-called granulomas in the lung tissue. Through
their research Dr Fenhalls and her team can now describe the different regions
in the granuloma, because of the way that the bacilli express their genes.
"When people first develop TB, non-necrotic granulomas form. They contain
cells from the human host which contain the bacilli - there is no 'zonation'
because the mycobacterial genes are expressed throughout the granuloma. We call
this a 'good' granuloma, because the bacilli are contained."
"But as the disease progresses, these granulomas change to become
necrotic. The granulomas now have a 'cheese-like' interior with no cells and the
bacilli can spread through the patient's coughing. In our study we found the
edge of the necrotic granuloma to contain human cells positive for the bacilli
genes. Then there is a 'transition zone' which contains some cells positive for
bacilli mRNA. The middle 'cheese-like' region contains no human cells or bacilli
gene expression, but contains bacilli DNA," she says.
"This distribution of gene expression suggests that different
micro-environments exist within the granulomas, to which the bacilli are
responsive, adopting different metabolic states. This ability to adopt different
metabolic states may enable them to survive the host immune system as well as be
resistant to medication - therefore they persist for a long time," she
explains.
Article courtesy of the MRC news
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