Researchers learned that a non-virulent strain of Coxiella burnetii (C. burnetii) bacteria, which typically causes Q Fever in humans, became virulent over time, according to a new study undertaken by scientists at the National Institute of Allergy and Infectious Diseases (NIAID). The researchers were then able to create a truly non-virulent form of that strain for safer use in research.
The discovery, unexpected by scientists who were running the study, was made after scientists discovered that “the weakened form of [C. burnetii] not typically known to cause disease naturally acquired an ability to do so.” They then “identified the genetic mutation responsible for the increased ability to cause disease (virulence) and created a form of the bacteria without the genetic flaw that could safely be used for research.”
C. burnetii “naturally infects livestock, including goats, sheep, and cattle.” It causes Q Fever in humans, which causes fewer than 1,000 cases per year in the United States but can in rare cases (fewer than 5 out of 100) cause “chronic Q fever, which develops months or years following the initial infection. This condition requires months of antibiotic treatment and can result in death.” Acute Q Fever is “characterized by mild-to-severe flu-like symptoms and can be treated with antibiotics.” Those at highest risk include “farmers, veterinarians, and animal researchers.”
The researchers set to find out how the length of lipopolysaccharide (LPS)—“a large molecule…[that] can profoundly influence a bacterium’s ability to cause disease in humans”—affected the bacteria’s virulence. The “wild type” of C. burnetii is “highly virulent and considered a select agent by the U.S. Centers for Disease Control and Prevention,” and there are three other strains – one highly virulent (NMI), one less virulent (NMC), one not virulent at all (NMII) – that are typically used for research.
The researchers infected guinea pigs with all three strains of the bacteria to “investigate how LPS length influences C. burnetii virulence.” The scientists found that NMII “isolates in the spleen of 3 of the 4 guinea pigs infected…suggesting that the bacteria disseminated in the animals rather than being immediately cleared.” The NMII isolates also were found to “feature an unrecognized form of LPS modification that helped produce elongated LMS and, therefore, became similarly virulent to the NMC strain.” A cellular culture confirmed these findings, and in response, the scientists created a new strain called “NMII-E” that “deleted the specific gene, and found that this strain did not produce the same LPS effects.”
The authors stated that these findings have “implications for laboratory work with C. burnetii, diagnostic sensitivity, and vaccine development. Specifically, the ability of the NMII strain to naturally revert to a more virulent form suggests that individual researchers who are working with the strain should perform their work in higher biosafety level conditions.” They also note that this work “demonstrates the success of the select agent program and advancement of safe alternatives for conducting important scientific research.”
NIH’s website has the news release.