Tuberculosis (TB) is an infectious bacterial disease that mainly affects the lungs. It is a major global public health problem.
often takes many months and till this day there is no effective vaccine.
Various TB bacterial strains exist globally, with different
‘The Lineage 4 tuberculosis strain can be genetically further subdivided into several sublineages. Some of these sublineages occur all over the world, others are geographically highly restricted.’
Only the so-called Lineage 4 occurs on all
continents. It is responsible for the majority of the 10 million new
infections and two million deaths annually.
Under the lead of Sébastien Gagneux at the Swiss Tropical and
Public Health Institute (Swiss (TPH), and DZIF scientist Stefan Niemann,
Research Center Borstel, a team of 75 scientists at 56 institutions
analyzed the genetic make-up of TB bacteria from several thousand
Surprisingly, it was found that Lineage 4 can be genetically
further subdivided into several sublineages. Some of these sublineages
occur all over the world, others are geographically highly restricted.
According to the study in the journal Nature Genetics
bacteria can be divided into generalists with worldwide distribution and
specialists that have focused on localized ecological niche. While
ecologists have been differentiating between generalists and
specialists, especially in plants, for a pathogen that transmits
exclusively from human to human, such a subdivision is new.
Generalists are immunologically more versatile than specialists
TB bacteria have a unique property: they hardly vary their antigens,
and are thus efficiently recognized by the human immune system. As a
result, a fierce immune reaction occurs, which affects the lungs in
particular, and promotes coughing. Thanks to this strategy, TB bacteria
is transmitted very efficiently from human to human.
The researchers show that the generalists pursue an additional
strategy. They show a slightly increased diversity of their antigens
compared to the specialists. "Generalists are thus able to react more
specifically to the immune system of different human populations," says
Stefan Niemann, who coordinates the research field "Tuberculosis" at
DZIF. They have adapted their molecular strategy and are able to push
through and spread much more globally.
Implications for vaccine development
These new findings have implications for the development of new TB
vaccines. The more TB bacteria can adapt their antigens, the more
difficult it will be to design a vaccine that is equally effective in
all human populations across the world. Hence, the development of a
broadly active TB vaccine might be delayed even further.
The international cooperation has made these results possible; for
the German Center for Infection Research scientists from the sites
Hamburg-Lübeck-Borstel, Munich and Tübingen have contributed to it as
well as scientists from the African Partner Institutions. "National and
international networks are the basis for the global fight against
infectious diseases as HIV and TB", says DZIF Prof Michael Hoelscher,
Director of the Tropical Institute in Munich, LMU.