New Method Can Rapidly Detect Potential Bioterror Agent causing Q fever
Modified Georgia Institute of Technology release
By Jane Sanders, Georgia Institute of Technology
September 6, 2005
Bacterial Bioterror: New Method Can Rapidly Detect Potential
Bioterror Agent and Pinpoint Bacterial Strain
A new combination of analytical chemistry and mathematical data analysis
techniques allows the rapid identification of the species, strain and
infectious phase of the potential biological terrorism agent Coxiella
burnetii. The bacterium causes the human disease Q
fever, which can cause serious illness and even death.
Research by the Georgia Institute of Technology and the Centers
for Disease Control and Prevention (CDC) has yielded a method that
proved to be 95.2 percent accurate in identifying and classifying Coxiella
burnetii. The laboratory test delivers results in about five minutes
compared to about two hours for the lab technique currently used to detect
“Because of its potential use as a bioweapon, we needed a method
to detect Coxiella burnetii at an early stage, and we needed
to be able to determine which strain is present so authorities can determine
the geographic area from which it came,” said Facundo
Fernandez, an assistant professor in the School
of Chemistry and Biochemistry at Georgia Tech. He presented the research
team’s findings Sept. 1 at the 230th American Chemical Society National
Meeting in Washington, D.C.
Fernandez and his Ph.D. student Carrie Young, a chemist in the CDC’s
Environmental Health Lab, collaborated with CDC researchers in the National
Center for Environmental Health and the National
Center for Infectious Diseases. They combined mass spectrometry —
an analytical technique to study ionized molecules in the gas phase —
and a mathematical data analysis technique called partial least squares
Mass spectrometry allows researchers to look at the profiles of different
proteins expressed in a microorganism. Partial least squares analysis
lets researchers separate important information from “noise”
— or biological baseline shifts caused by sample preparation variations
— that could corrupt a predictive model.
Not only is the combination of these techniques into one method a novel
concept, this research also represents the first time that Coxiella
burnetii has been detected at the strain level with a rapid detection
process, Fernandez noted. Such classification is a challenging task with
bacteria, he added. Researchers believe the technique also will work with
other pathogens, which they expect to begin studying this fall.
Coxiella burnetii is a species of concern because it causes
the highly infective human disease Q fever, which is transmitted primarily
by cattle, sheep and goats. A human can be infected by as few as one bacterium.
The disease can be manifested as a chronic or acute case, depending on
the strain. Symptoms can include high fever, severe headache, vomiting,
diarrhea, abdominal pain and chest pain. Q fever can also lead to pneumonia
and hepatitis. The chronic form of the disease can cause endocarditis,
an infection of a heart valve, and even lead to death.
In addition to being a public health threat, Coxiella burnetii
is listed as a Category B bioterrorism agent because of its long-term
environmental stability, resistance to heat and drying, extremely low
infectious dose, aerosol infectious route and history of weaponization
by various countries, according to the CDC.
To date, Georgia Tech and CDC researchers can differentiate between
seven Coxiella burnetii strains, which come from Australia, the
United States and Europe. Some strains are more infective than others,
and the researchers’ method determines not only the strain, but
whether it’s a Phase I or II strain depending on its ability to
infect, Fernandez explained.
“The next step is to fine tune our model and increase the number
of strains we can identify,” Fernandez said. “There is a library
of strain samples available to us, though the samples are sanitized with
gamma radiation and rendered inactive before analysis.” To identify
strains, researchers examine the appearance of biomarker proteins in samples.
“In some cases, we classify a strain by the presence or absence
of a biomarker. And sometimes we see the same biomarker proteins, but
at varying levels, in different strains,” Fernandez noted.
The researchers’ detection technique is highly sensitive, meaning
it can detect Coxiella burnetii strains at very low concentrations
– specifically at the attomole level, which is equivalent to 1 X
10-17 moles. (Moles measure the actual number of atoms or molecules in
Until now, the best method to differentiate between strains of Coxiella
burnetii was a laboratory technique called polymerase chain reaction
(PCR), which analyzes the genes of a bacterium and yields results in one
to two hours. The new method, which analyzes the proteins of a bacterium,
can yield results in five minutes. For now, it is also a laboratory test,
though separate research involving Fernandez and other Georgia Tech researchers
is pursuing development of a field-testing instrument.
“In a bioterrorism event, you want more than one method to determine
the strain you are dealing with,” Fernandez noted. “So you
would use our technique first and then use PCR as a second method to independently
confirm your results. Also, our method using mass spectrometry, allows
you to quickly replicate your analysis – even 10 times if you want
to. That gives you an added degree of statistical significance.”
Fernandez and his colleagues began the research in June 2004 with funding
from the CDC and a Georgia Tech Research Corporation seed grant. With
their encouraging results about the method’s capability, they plan
to apply for additional federal funds in the near future.
Working with Fernandez and Young are John Barr and his colleagues Adrian
Woolfitt and Hercules Moura of the National Center for Environmental Health,
and Edward Shaw (now at Oklahoma State University) and Herbert Thompson
of the National Center for Infectious Diseases.
RESEARCH NEWS & PUBLICATIONS OFFICE
Georgia Institute of Technology
75 Fifth Street, N.W., Suite 100
Atlanta, Georgia 30308 USA
MEDIA RELATIONS CONTACTS:
1) Jane Sanders (404-894-2214); E-mail: jane.sanders[AT] edi.gatech.edu);
2) John Toon (404-894-6986); E-mail: (john.toon [AT] edi.gatech.edu)
3) National Center for Environmental Health, CDC (404-498-0070); E-mail:
(atsdric [AT] cdc.gov)
1. Facundo Fernandez, Georgia Tech (404-385-4432); E-mail: (facundo.fernandez [AT] chemistry.gatech.edu)
2. John Barr, CDC (770-488-7848); E-mail: (JBarr [AT] cdc.gov)
WRITER: Jane Sanders
This is a modified news release from the Georgia Institute of Technology. The original can be found at Bacterial Bioterror: New Method Can Rapidly Detect Potential Bioterror Agent and Pinpoint Bacterial Strain.