Profs study deadly germ seen in Iraq

Yale researchers are waging their own war against an invisible enemy in Iraq — a strain of multiresistant bacteria that has infected over 700 soldiers and been associated with seven deaths since 2003.

According to research published today in Genes and Development, a Yale team has identified 16 “alien islands” on the genome of Acinetobactar baumannii that are responsible for its virulence. The bacteria targets individuals with compromised immune systems, making Iraqi soldiers who suffer traumatic wounds ideal hosts for the “superbug.” The lab, which is led by Yale professor Michael Snyder, is responsible for developing the first complete sequence of the microbe’s genome.

“Alien islands” are DNA segments that the bacteria acquires from other microorganisms and retains if they provide a survival benefit.

“[A. baumannii] is a pathogen on the rise,” Snyder said. “It has become a more serious health concern in recent years, especially since it has evolved into more and more resistant forms.”

A. baumannii, thought to reside in soil and water, can, if left untreated, cause pneumonia, meningitis, respiratory infections, sepsis and urinary tract infections. Upon infection, the organism has a casualty rate of 75 percent.

“The Department of Defense is very concerned,” Snyder said. “There was an outbreak of the bacteria in Iraq. It’s clear that we’re dealing with a number of resistant strains.”

Col. Bruno Petrucelli, the U.S. Army’s senior epidemiologist, said the organism’s resistance to most drugs as well as its high casualty rate makes it potentially very dangerous.

“Once it has established itself, it is difficult to eliminate,” Petrucelli said.

A. baumannii has become one of the most common sources of infection among American troops in Iraq, which has a climate very supportive of the bug. The strain typically infects soldiers through wounds while they are in the battlefield or at military medical facilities.

Snyder said the pathogenic genes identified by the group may help researchers target effective antimicrobial drugs as well as provide insight into the mechanisms by which bacteria develop virulence.

“The study provides the foundation for researchers to build a drug effective against the bacteria,” said Tara Gianoulis, a researcher in professor Mark Gerstein’s lab, which collaborated with Snyder’s lab on the study. “There’s still a lot of work to be done in characterizing these segments, but [our work] provides a nice molecular toolbox.”

The research group used cutting-edge technology, including 454 sequencing, a genomic sequencing technique developed by the Branford-based company 454 Life Sciences, and transposon mutagenesis in their research.

“[454 sequencing] is a highly efficient technique that allows us to sequence microbial genomes at less than the price of a car,” Snyder said, adding that the technique allowed them to sequence the bacteria’s genome in a matter of weeks.

Mutagenesis involves deactivating genes thought to be pathogenic to see if the organism is virulent in their absence, Gianoulis said. If the bacteria’s ability to infect a host organism is reduced or eliminated when certain genes are removed, those genes are implicated in its virulence.

The group identified genes to test by comparing the genome of the bacteria to that of its nearest relative, which is not virulent, Gianoulis said. If A. baumannii contained a stretch of DNA not present in the related species, Gianoulis said, it was isolated as a candidate.

“If you imagine DNA as a string of words, [these candidate segments] are the words missing on the benign species,” she said.

Computational techniques, which allowed the lab to organize the bacteria’s genome into patterns, also enabled them to identify these “alien” segments based on their divergence from such patterns, she said.

“In a bacteria, you not only have the host bacterial DNA but also [that which] … has been taken from other bacteria,” said Gianoulis. “[These segments] can be selected because they are wildly different from the rest of the genome.”

The research follows a study the lab conducted in 2005 that found that ethanol stimulates the virulence of A. baumannii.

Snyder said the group hopes to continue researching the biology of the bacteria, including the triggers that activate its virulence and the toxins it releases upon infection of a host.

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