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Researchers now are focused on tweaking the device so that it can
provide a complete toxin profile of staph that will quickly reveal the
virulence of infections. To accomplish that goal, researchers from the
university�s Center of Biomedical Research Excellence (COBRE) are
partnering with CAMBR scientists.
Eventually, it is hoped that even the hard-to-identify MRSA bacteria
will be detected quickly using some iteration of the nanotechnology.
MRSA�s resistance to antibiotics has earned it �superbug� status. It
is responsible for more 94,000 infections and 16,000 deaths annually
in the U.S. alone, according to recent Center for Disease Control
reports. Those numbers indicate it is a greater health threat to
Americans than the AIDS virus.
The spiking MRSA death toll recently reported by the Center for
Disease Control presents formidable motivation to move infectious
disease research ahead, and to get life saving nanotechnologies into
the marketplace. University of Idaho scientists are focused on both
goals.
The CAMBR Biosensor
The vast majority of hospitals, including all regional facilities in
Coeur d�Alene, Idaho, and Spokane, Wash., still culture staph in Petri
dishes. The culture usually takes one to two days to mature until it
is identifiable. CAMBR biosensors identify staph within three hours,
with an equally astounding increase in accuracy. The device already
has successfully detected the staphylococcus aureus 16S rRNA gene, 16S
rRNA, and enterotoxin B, as well as a biomark for lung cancer.
�Our electronic detection capability is approximately 1,000 times more
sensitive than the chemilumine technologies currently being used in
clinical laboratories,� said Wusi Maki, principal investigator for
CAMBR biomolecular research.
�Our plan is to work with Professor Greg Bohach and use the nanosensor
CAMBR has developed to provide a toxin profile that will tell us very
quickly, and very accurately, if we are looking at lethal or just mild
staph,� said Maki.
Bohach is principal investigator and director of the COBRE in the
university�s Department of Microbiology, Molecular Biology and
Biochemistry (MMBB).
There currently is no method available to quickly and accurately judge
the virulence of staph bacteria, Bohach noted.
Finding effective �capture molecules,� those that adhere specifically
to staph and its toxins, is key to creating a biosensor-generated
toxin profile and insights into the virulence of specific staph
infections.
Finding an RNA Fragment in a Molecular Library Stack
University of Idaho MMBB graduate student Ryan Dobler has been working
with Bohach and scientists at CAMBR labs to identify and replicate
capture molecules. Specifically, he has been searching through a vast
molecular library looking for an aptamer molecule, �a piece of RNA
that binds to a target,� Dobler explained.
His work has confirmed that the large pool of RNA fragments he studied
are binding; specifically, that they attach to fibronectin binding
protein. �Fibronectin binding protein is a unique protein that�s found
on the surface of staph bacteria,� Dobler said. �It helps bind the
staph to human tissue.�
The research has not yet yielded an aptamer that would most
effectively and most specifically recognize staph. In his year-long
investigation, Dobler tested about 80 samples among the thousands that
may yield results.
He is writing up his research, and will present his findings in his
master�s thesis in December. Bohach, Maki and their teams hope to find
funding to continue the study.
�A good example of capture molecules are those that attach themselves
to the toxins that staph makes,� Bohach explained. �We hope to
identify particularly those toxins that are associated with the more
virulent strains, including MRSA strains. There�s quite a bit known
about the toxins, and we can � in a limited number of steps � screen
and isolate staph for many different toxins at the same time.�
�So if you�re looking specifically for MRSA, you could look for those
bacterial molecules that are associated with it, and through that
unique association, identify it with precision,� he said.
As the research progresses, capture molecules for a variety of
identifying toxins will be incorporated onto the biosensor, which will
quickly read and accurately translate the toxin profile.
Using staph Pathogenesis as a Treatment Delivery System
Bohach and others members of his team also are looking at the
mechanisms staph bacteria employ to enter host cells and proliferate.
Using nanowires and other nanomaterials (NMs), they aim to hijack the
methods bacteria use for toxin delivery, and use them to deliver drug
therapies specifically to infected cells.
Bohach is working with University of Idaho professor of physics and
materials engineer David McIlroy, microbiologist Carolyn Hovde and
others to develop nanowires and other nanomaterials (NMs) for use as
innovative drug delivery systems.
McIlroy leads a team of seven researchers supported by the
university�s Blue Ribbon Strategic Initiative funding. Their goal is
to integrate nanonmaterials research with cell biology and bioscience
research.
The Idaho researchers have found that NMs penetrate tumors easily, and
can do so coated with antibodies or other materials that seek and
destroy infected cells, while sparing normal cells.
They are looking for ways to enable NMs to more readily penetrate the
targeted cells, and they report that nanowires coated with the protein
fibronectin penetrate cells more easily than uncoated nanowires. In
experiments with human and animal cells, they have illustrated that
coated nanowires can enter and deliver a toxic agent (StxA1) that
kills the cells.
Microbiologists Bohach and Hovde work with CAMBR scientists including:
Maki, biochemist; Shiva Restage, organic chemist; Miramar Mishap,
surface chemist and nanofabrication expert; and Brian Filanoski, a
biochemist studying optical detection of bio-agents.
University of Idaho CAMBR biosensor breakthroughs have recently
generated two patent applications. The technology is at the
demonstration phase and work is needed to bring it to a marketable
system, said Maki. �All the building blocks are in place to produce a
real system. With the right investment and focus, the technology could
be made ready by the teams in Post Falls and Moscow in a few years,"
she said.
The technology developers have experience delivering commercial
technologies, and that task is within the charter of the CAMBR
organization, she added.
Once developed and adopted for use in hospitals, biosensors would
impact both those who test positive and those who test negative for
the bacteria. For the duration of the current one to three day wait
for a staph culture, hospitals must isolate the patient. Insurance
seldom covers that expense, so patients and hospitals currently pick
up the hefty tab.
�There is an immediate need for faster, more accurate staph detection,�
said Maki. �Quick identification in hospitals could save many lives,
and millions of dollars.�
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