Scientists from the Virginia Bioinformatics Institute (VBI) at Virginia
Tech, the University of Maryland School of Medicine, and the University
of Louisville have revealed that genes for a specific type of molecular
secretion system in Rickettsia, a structure that is linked in many
cases to virulence, have been conserved over many years of evolution.
The scientists compared the gene sequences of 13 Rickettsia species
to detect a highly conserved type IV secretion system. Type IV
secretion systems are membrane-spanning transporters that can act as
syringes that inject virulence factors into the cells of their hosts
(eukaryotes). Once introduced, these virulence factors compromise the
host and may result in harmful disease, for example Legionnaires’
disease (Legionella pneumophila) and Q fever (Coxiella burnetii).
However, these secretion systems have not been implicated in human
diseases caused by Rickettsia, including epidemic typhus (R.
prowazekii) and Rocky Mountain spotted fever (R. rickettsii). Type IV
secretion systems are unique in their ability to transport nucleic
acids and proteins into plant and animal cells. A possible role of the
transporter that is not directly associated with virulence, such as DNA
transfer, has been overlooked in Rickettsia.
Dr. Joseph Gillespie, a bioinformatician at the Virginia
Bioinformatics Institute and leader of the study, remarked: "We have
used the Rickettsia genomic information steadily accumulated over the
past 10 years as a starting point to look in detail at the origin and
function of Rickettsia virulence-like genes. The study reveals a highly
conserved type IV secretion system across the 13 genomes investigated,
some of which are, intriguingly, not known to cause disease in their
invertebrate and vertebrate hosts."
In addition to the evolutionarily conserved nature of the Rickettsia
type IV secretion system, informatics analysis revealed some unexpected
properties, including gene duplication of nearly half of its
components. Gene duplication is very rare in Rickettsia genomes. By
digging a little further, the team also identified three additional
genes that likely contribute to the secretion system. Gillespie noted:
"Because Rickettsia live inside their hosts at all stages of their life
cycle, we are very limited in how we can characterize their genes.
Researchers often have little choice but to apply related information
from other bacteria that are easier to study." This often entails
labor-intensive manual work that cannot currently be substituted by
automated gene prediction methods. "Sometimes, the brain beats the
algorithm," Gillespie added.
One of the major revelations of the sequence comparison is that the
ancestor organism of the Rickettsia most likely acquired a
virulence-like genetic locus from distantly related bacteria. The team
speculates that this may have taken place while the ancestor was
residing in a protozoan host.
Principal Investigator Bruno Sobral remarked: "Virulent species of
Rickettsia are of great interest both as emerging agents of infectious
disease and potential bioterror agents. However, a lot of intense
laboratory work has failed to provide information that characterizes
their virulence factors. Our comparative genomics approach sheds light
on the evolution of Rickettsia virulence and provides a solid
foundation for the future laboratory assessment of the function of the
Rickettsia type IV secretion system."
Dr. Gillespie concluded: "Additional experimental evidence from
recent studies suggests that some of the components of the Rickettsia
type IV secretion system are indeed expressed, regulated and secreted.
It is too early yet to know with certainty the precise mechanism of how
the system operates but we now have a solid foundation for future work."
Source : Virginia Tech