Scientists have sequenced the entire genome of a sexually transmitted bacterium, Ureaplasma urealyticum, that infects an estimated 60 percent to 80 percent of adults and, if passed on to newborn infants, can cause in them meningitis, pneumonia, and even death.
"The results of this project add to the rapidly growing list of pathogenic
microbes whose genomes have been sequenced," says Anthony S. Fauci, M.D.,
director of the National Institute of Allergy and Infectious Diseases
(NIAID), which helped support the research. "This breakthrough will lead to
a much better understanding of how U. urealyticum causes disease, and should
allow scientists to devise better treatments against it."
"Although this knowledge will not immediately lead to a cure, it will put
tools in people's hands," says John Glass, Ph.D., who performed much of the
sequencing while a postdoctoral fellow at the University of Alabama at
Birmingham (UAB). Dr. Glass, now a researcher at Eli Lilly and Company, is
lead author of a paper, published in the current issue of Nature, that
describes the genome sequence.
"We know very little about this organism compared with others that cause
disease in humans," says senior author Gail H. Cassell, Ph.D., formerly at
UAB but now vice president for infectious disease research and clinical
investigation at Eli Lilly and Company. The sequence should help clear up
several questions scientists want answered about U. urealyticum, she said.
For instance, the majority of pregnant women are infected by this bacterium,
but in most cases it does no harm. "The enigma surrounding this organism is
that it appears to cause disease in only a sub-population of infected
people," Dr. Cassell says. "The sequence will help us understand why that is
so." It will also help scientists better understand what allows U.
urealyticum to invade intact fetal membranes and infect the placenta and
amniotic fluid, she notes.
Scientists also want to understand the genetic and molecular mechanisms
behind U. urealyticum's propensity to cause disease. Preliminary analyses
of its genome did not find certain disease-causing genes known to exist in
other bacteria. However, some studies have shown that U. urealyticum causes
tissue damage, so Dr. Glass suspects such "virulence" genes exist in the
bacterium, but that they're different enough from known genes that
scientists will have to look harder to find them. Scientists might even
discover a whole new class of such genes, Dr. Glass speculates.
Despite their many questions, the researchers do have some answers. Here
are highlights from the initial analysis of the genome:
- The genome of U. urealyticum is the second smallest of any sequenced
microbe, consisting of only 751,719 DNA base pairs. (For comparison, a
typical bacterium has millions of base pairs of DNA, and the human genome
contains about 3 billion.).
- The U. urealyticum genome consists of 652 genes, half of which have
unknown functions. Some of these mysterious genes are similar to genes
identified in other organisms, but more than half of them have never been
- This bacterium has a novel metabolic system. Like all bacteria of the
genus Ureaplasma, it can "digest" urea, a substance commonly found in urine.
But U. urealyticum apparently possesses enzymes that metabolize urea
differently than any known bacteria.
The genome sequence of U. urealyticum will be compared with the sequences of
other sexually transmitted bacteria in order to search out any
commonalities. "The sequence is now available in a relational database
designed to make comparisons between organisms that damage the reproductive
tract," says project officer Penelope J. Hitchcock, D.V.M., chief of NIAID's
Sexually Transmitted Disease branch. To date, the genomes of five
STD-causing bacteria have been sequenced with NIAID support, and that
information, along with the gene sequences of other STD pathogens, is made
widely available to researchers via the STDGEN Web site at
Finally, the U. urealyticum genome was sequenced with a new technique,
developed at PE Biosystems, that allowed just two researchers using one
automated sequencing machine to complete the work in 21 months. The
effectiveness of such a "micro-sequencing center" may encourage other small,
academic labs to take on genome projects of their own.
JI Glass et. al. The complete sequence of Ureaplasma Urealyticum: alternate
views of a minimal genome and mucosal pathogen. Nature 407(6805):757-62