Colorado State University Researchers Find Deadly Bacteria Becoming Resistant in New Way

A team of Colorado State University researchers has co-directed a study that found that the organism that causes melioidosis — and which is considered at top biothreat for potential use in an act of terrorism — can become resistant to the antibiotic most commonly used to treat it by mutating in a way scientists have never seen before. The study holds important clues for treating melioidosis and for future studies that may help unlock the strategies bacteria use to become resistant to antibiotics.

Melioidosis is a deadly disease if not treated quickly and with the right antibiotic, usually ceftazidime. It is caused by the bacteria Burkholderia pseudomallei.

Typically, bacteria have been known to mutate or change to become resistant to antibiotics by making a small but effective change in their DNA. Researchers on this project, co-directed by Herbert Schweizer, a researcher in the university’s Department of Microbiology, Immunology and Pathology, discovered that the bacteria completely discarded an entire section of it is DNA to develop resistance to a key drug used to treat it. This research was prompted when doctors began to notice that a significant number of cases treated with the standard antibiotic ceftazidime did not improve.

“To see a bacterium remove large portions of its own DNA is surprising because it’s almost like bacterial suicide,” Schweizer said. “The bacteria are weakened by this change — evidenced by the fact that they grow very slowly in typical conditions. Its slow growth helped it elude proper treatment because it didn’t show up on tests which depended upon seeing bacteria multiply in the test media that Burkholderia pseudomallei typically thrives in. This new mutant form of the bacterium we looked at in this study was likely responsible for a good portion of about 11 to 17 percent of the cases of melioidosis that did not respond to ceftazidime treatment.”

Schweizer said that it was surprising to see the DNA of the bacterium change so significantly and still cause disease.

“The ultimate outcome of this research is that, when patients don’t respond to ceftazidime, we now know what to look for. And hospitals can begin using new tests to diagnose the problematic mutant strains early and patients can then be treated with other antibiotics that may be more effective against the resistant strains,” Schweizer said.

Burkholderia pseudomallei is considered an important research priority by the U.S. government because it is not commonly seen in other areas of the world and could be used as a bioweapon. The bacteria are found in water and soil in areas of Thailand and Australia, and melioidosis is also becoming an emerging disease in India and other parts of the world. It is not found in the United States other than rare cases contracted by people while traveling abroad. Because it is not common in the U.S. and other countries but is deadly and requires only a small amount to cause illness, it is considered a biological weapon threat. It has historically been researched for use as a biological weapon.

The mortality rate of melioidosis in some parts of the world is still as high as 40 percent even if diagnosed and treated swiftly. It causes pneumonia and other infections in people and many animals including goats, cattle, sheep, dogs and cats.

Schweizer conducted the research as part of the projects located in the University’s Rocky Mountain Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, a consortium of researchers from around the West devoted to finding tests, cures and preventions for some of the world’s most deadly infectious diseases, with efforts devoted to national and global health as well as part of the nation’s biosecurity strategy.

The research team in this study includes former CSU graduate student Drew A. Rholl and also is comprised of scientists from Mahidol University in Bangkok, Thailand; Genome Institute of Singapore; University of Cambridge; and Oxford.

The research findings were published in today’s issue of the Proceedings of the National Academy of Sciences.