Transcript Two salmonellas (E Jakobsson)

The Two Salmonella’s: A case history in the role of open
scientific inquiry in the fight against bioterrorism and
infectious disease.
Eric Jakobsson, Department of Molecular and Integrative
Physiology, National Center for Supercomputing Applications,
University of Illinois at Urbana-Champaign
We now have the complete genomic sequences of two
Salmonella’s: Salmonella typhi and Salmonella typhimurium.
Typhi:
•Causes typhoid fever, which is lethal in a high
fraction of untreated cases.
•Is rare in industrialized countries due to public
health, but kills estimated 600,000 people per year
world-wide.
•Significant and growing fraction is multi-drug
resistant.
•Does not persist in the food supply; needs a human
as a host and vector of infection (the famous
Typhoid Mary)
Typhimurium:
•Causes gastroenteritis, always miserable but
rarely fatal.
•Persists in food supply, from which it readily
spreads to humans (Salmonella typhimurium was
the agent in the largest bioterrorism attack in US,
which was done through restaurant salad bars in
Oregon)
•Significant and growing fraction is multi-drug
resistant
Comparative Facts between typhi and typhimurium
•Many genes are almost identical.
•Typhimurium genome codes for more proteins.
Many genes in typhimurium are psuedo-genes in
typhi.
•Genetic bases of virulence factors in typhi are
pretty well-known.
•Genetic bases for typhimurium being able to
persist in wider environment are not known exactly,
but are presumably in the genes that typhimurium
has and typhi lacks.
•Genetic bases for multi-drug resistance are pretty
well known.
Weaponization of Salmonella consideration leads to:
Big question #1: Would it be possible to use genomic
knowledge to engineer a super-lethal Salmonella combining
multi-drug resistance, typhi’s virulence, and typhimurium’s
ability to persist in the food supply?
AAnswer: Probably. In fact, almost certainly.
Overcoming the threat of multi-drug resistant typhi
and typhimurium consideration leads to:
•Big question #2: Since it is predictable that broadspectrum antibiotics will become useless against both
typhi and typhimurium, isn’t it necessary to use genomic
knowledge to design Salmonella-specific drugs to
combat naturally occurring Salmonella infections?
Answer: Yes
The Salmonella dilemma: Dissemination of genomic
knowledge of Salmonella can facilitate bio-weapons
development but is necessary to combat Salmonella
infection. What to do?
•Alternative 1: Restrict dissemination of genomic
knowledge. In the short term, this may hinder development
of “super-Salmonella” terror weapon, but in the long run
leaves us at the mercy of multi-drug resistant Salmonella
strains ranging from incapacitating to lethal.
•Alternative 2: Disseminate genomic knowledge, but
strongly support development of Salmonella-specific drugs.
The knowledge may provide a rogue state with the ability to
develop “super-Salmonella” terror weapon, but it provides
us with the opportunity to defend against all Salmonella
infection, from either terrorist or natural source.
The Salmonella dilemma is not only the Salmonella
dilemma. Any major bacterial disease that is
common in the non-industrialized world poses
exactly the same issues.
Conclusion: The right policy course is to freely
disseminate knowledge of bacterial genomes, at the
same time embarking on a vigorous program to use
that knowledge for design of specific antimicrobial
drugs to replace the broad spectrum antibiotics that
are predictably on a path to becoming useless.