Structure of Salmonella bacteria imaged at near atomic scale
14 March 2011
Scientists at the Research Institute of Molecular Pathology in
Vienna have imaged in unprecedented detail the needle-shaped extensions
that Salmonella bacteria use to infect their host.
The scientists employed recently developed methods of
cryo-electron microscopy and have been able to clarify the structure
of this infection apparatus on the near-atomic scale.
Some of the most dreaded
diseases in the world such as plague, typhoid and cholera are caused
by bacteria that have one thing in common: they possess an infection
apparatus which is a nearly unbeatable weapon. Detailed knowledge of the needles’
structure may help to
develop substances that interfere with its function and thus prevent
When attacking a cell of the body, Salmonella bacteria develop numerous
hollow-needle-shaped structures that project from the bacterial
surface. Through these needles, the bacteria inject signal
substances into the host cells that re-program these cells and
thereby overcome their defense. From this time on
the pathogens can invade the cells unimpeded and in large
The biochemist and biophysicist Thomas Marlovits, a group leader
at the Vienna Institutes IMP (Research Institute of Molecular
Pathology) and IMBA (Institute of Molecular Biotechnology) has been
occupied for several years with the infection complex of
As early as in 2006 Thomas Marlovits showed how the
needle complex of Salmonella typhimurium develops (Nature 441,
637-640). Together with his doctoral student Oliver Schraidt he has
now been able to demonstrate the three-dimensional structure of this
complex in extremely high resolution.
The team was able to show
details with dimensions of just 5 to 6 angstroems, which are nearly
atomic orders of magnitude. Their work will be presented in the
forthcoming issue of the journal Science.
Structure of the needle-complex of Salmonella,
embedded in a cellular context (artist’s interpretation based on
original data). Source: IMP-IMBA.
High precision microscopy
Never before has the infection tool of salmonellae been presented
in such precision. This was achieved by the combined use of
high-resolution cryo-electron microscopy and specially developed
'Austria’s coolest microscope' makes it possible
to shock-freeze biological samples at minus 196 degrees
centigrade and view them in almost unchanged condition. However,
when 'zooming in' on their object, scientists are confronted with
a treacherous problem: the high-energy electron beam falls at such
high concentrations on the sample that the latter is destroyed
after the very first image.
The Viennese scientists have resolved
the problem by developing new image-processing algorithms and
with sheer numbers of images. They analyzed about 37,000 images of
isolated needle complexes. Similar images were grouped and computed
jointly. By doing so they were able to generate a single sharp
image from numerous blurred ones. This enormous computing power
was created by a cluster of about 500 interconnected computers.
Microscopy without the human interference factor
The microscope works in semi-automated fashion at night to obtain
the large number of images. This is very advantageous because human
beings merely interfere with the job. They breathe, speak, move, and
thus unsettle the sensitive microscope. Even a moving elevator may
irritate the electron beam.
The cryo-electron microscope at IMP-IMBA is the only one of its
kind in Austria. The immense technical effort associated with its
operation pays off, as far as the scientists are concerned.
Advancing into the subnanometer range created a further means of
expanding their knowledge. They were able to 'adjust' existing data
(obtained from crystallography) to the needle structure and thus
complement the three-dimensional image in a perfect manner. The
use of this hybrid method enabled the scientists to elucidate the
complete construction plan of the infection apparatus.
Marlovits regards this technology as an innovation boost: "Using the
methods we developed for our work, we were able to establish imaging
standards at a very high level. We can explore its absolute limits
with the aid of the fantastic infrastructure we have here at Campus
This knowledge not only
advances basic research. "Using our data, we may well be able to
find a compound that interferes with the needle complex and
disturb its function," says Marlovits. "We would then have a very
effective medication — one that combats not only salmonellae but
also other pathogens that employ this system, such as pathogens that
cause cholera, plague or typhoid."
Oliver Schraidt & Thomas C. Marlovits. Three-Dimensional Model of
Salmonella’s Needle Complex at Subnanometer Resolution. Science,
March 4, 2011