  The gram-negative bacterium Yersinia pestis, the aetiological agent of
bubonic plague, is one the deadliest pathogens known to man. Despite its
historical reputation, plague is a modern disease which annually afflicts
thousands of people. Public safety considerations greatly limit clinical
experimentation on this organism and thus development of theoretical tools to
analyze the capabilities of this pathogen is of utmost importance. Here, we
report the first genome-scale metabolic model of Yersinia pestis biovar
Mediaevalis based both on its recently annotated genome, and physiological and
biochemical data from literature. Our model demonstrates excellent agreement
with Y. pestis known metabolic needs and capabilities. Since Y. pestis is a
meiotrophic organism, we have developed CryptFind, a systematic approach to
identify all candidate cryptic genes responsible for known and theoretical
meiotrophic phenomena. In addition to uncovering every known cryptic gene for
Y. pestis, our analysis of the rhamnose fermentation pathway suggests that betB
is the responsible cryptic gene. Despite all of our medical advances, we still
do not have a vaccine for bubonic plague. Recent discoveries of antibiotic
resistant strains of Yersinia pestis coupled with the threat of plague being
used as a bioterrorism weapon compel us to develop new tools for studying the
physiology of this deadly pathogen. Using our theoretical model, we can study
the cells phenotypic behavior under different circumstances and identify
metabolic weaknesses which may be harnessed for the development of
therapeutics. Additionally, the automatic identification of cryptic genes
expands the usage of genomic data for pharmaceutical purposes.
