Many strains of e-coli, gram negative rods, readily form sexual pilia
and swap DNA with bacteria of other species. They also produce soluble
beta amyloid, which they catylise out of solution to form a steel wool
style matrix of filaments all out of proportion to their size and
number which allows less talented microbiota to attach.
So far a big difference between healthy sinuses and CS sinuses has
been that no gram negative rods are reported in healthy sinuses, while
a few gram negative rods are frequently reported in CS sinuse
smears.

Now the University of North Carolina has found that the bisphosphonate
drugs clodronate and etidronate
block a key enzyme Relaxase that allows e-coli to open it's cell
membrane, swap DNA and spread resistance genes. It also kills the e-
coli that carry the enzyme. If Relaxase is conserved in other bacteria
species it could kill them as well. This could be huge. Didronel is an
approved and available drug so it could be prescribed with antibotics
tommorow.  How useful this combination is will depend on how well it
penetrates the biofilm, but there are no regulatory barriers.

I am not a big fan of the chronic use of bisphosphonates as they are
often prescribed to prevent osteoporosis because over the long term
they can cause complications with the bone renewal balance of the jaw
and teeth and I am pretty sure that you would not want to take it in
combination with predisone. However there should be a history to check
for safety when used in conjunction with various antibotics  as they
are currently prescribed along with antibiotics to patients that have
had hip replacement surgery.

http://www.sciencedaily.com/releases/2007/07/070709171636.htm
Source:      University of North Carolina at Chapel Hill
Date:     July 12, 2007
    More on:
Bacteria, Pharmacology, Microbes and More, Infectious Diseases,
Microbiology, Extreme Survival
New Way To Target And Kill Antibiotic-resistant Bacteria Found

Science Daily - Putting bacteria on birth control could stop the
spread of drug-resistant microbes, and researchers at the University
of North Carolina at Chapel Hill have found a way to do just that.

Antibiotic resistance propagates in bacteria by moving DNA strands
containing the resistance genes to neighboring cells. An enzyme called
relaxase is essential for this process. Bisphosphonates, already
approved to treat bone loss, have now been shown to potently disrupt
the relaxase function. Some bisphosphonates prevent the transfer of
antibiotic resistance genes and selectively kill bacterial cells that
harbor resistance. (Credit: Scott Lujan, University of North Carolina
at Chapel Hill)

The team discovered a key weakness in the enzyme that helps "fertile"
bacteria swap genes for drug resistance. Drugs called bisphosphonates,
widely prescribed for bone loss, block this enzyme and prevent
bacteria from spreading antibiotic resistance genes, the research
shows. Interfering with the enzyme has the added effect of
annihilating antibiotic-resistant bacteria in laboratory cultures.
Animal studies of the drugs are now underway.

"Our discoveries may lead to the ability to selectively kill
antibiotic-resistant bacteria in patients, and to halt the spread of
resistance in clinical settings," said Matt Redinbo, Ph.D., senior
study author and professor of chemistry, biochemistry and biophysics
at UNC-Chapel Hill.

The study provides a new weapon in the battle against antibiotic-
resistant bacteria, which represent a serious public health problem.
In the last decade, almost every type of bacteria has become more
resistant to antibiotic treatment. These bugs cause deadly infections
that are difficult to treat and expensive to cure.

Every time someone takes an antibiotic, the drug kills the weakest
bacteria in the bloodstream. Any bug that has a protective mutation
against the antibiotic survives. These drug-resistant microbes quickly
accumulate useful mutations and share them with other bacteria through
conjugation -- the microbe equivalent of mating.

Conjugation starts when two bacteria smoosh their membranes together.
After each opens a hole in their membrane, one squirts a single strand
of DNA to the other. Then the two go on their merry way, one with new
genes for traits such as drug resistance. Many highly-drug resistant
bacteria rely on an enzyme, called DNA relaxase, to obtain and pass on
their resistance genes. A mutation that provides antibiotic resistance
can sweep through a colony as quickly as the latest YouTube hit.

The researchers analyzed relaxase because it plays a crucial role in
conjugation. The enzyme starts and stops the movement of DNA between
bacteria. "Relaxase is the gatekeeper, and it is also the Achilles'
heel of the resistance process," Redinbo said.

Led by graduate student Scott Lujan, the team suspected they could
block relaxase by searching for vulnerability in a three-dimensional
picture of the relaxase protein. Lujan, a biochemistry graduate
student in the School of Medicine, confirmed the hunch using x-ray
crystallography, which creates nanoscale structural images of the
enzyme.

The researchers predicted that the enzyme's weak link is the spot
where it handles DNA. Relaxase must juggle two phosphate-rich DNA
strands at the same time. The team suspected a chemical decoy -- a
phosphate ion -- could plug this dual DNA binding site. Redinbo, who
has a background in cancer and other disease-related research,
realized that bisphosphonates were the right-size decoy.

There are several bisphosphonates on the market; two proved effective.
The drugs, called clodronate and etidronate, steal the DNA binding
site, preventing relaxase from handling DNA. This wreaks havoc inside
E. coli bacteria that are preparing to transfer their genes, the
researchers found. Exactly how bisphosphonates destroy each bacterium
is still unknown, Redinbo said, but the drugs are potent, wiping out
any E. coli carrying relaxase. "That it killed bacteria was a
surprise," he said. By targeting these bacteria, the drugs act like
birth control and prevent antibiotic resistance from spreading.

Redinbo, who cautions that the results only apply to E. coli, said
further testing will reveal whether bisphosphonates also attack
similar species like Acinetobacter baumannii (hospital-acquired
pneumonia), Staphylococcus aureus (staph infections) and Burkholderia
(lung infections).

"We hope this discovery will help existing antibiotics or offer a new
treatment for antibiotic-resistant bacteria," he said.

The drugs may be most effective at sites where clinicians can best
control dosage -- on skin and in the gastrointestinal tract, Redinbo
said. Other applications may include disinfectants and treatments for
farm animals.

Study coauthors, all from UNC-Chapel Hill, include Laura Guogas,
Heather Ragonese and Steven Matson. Redinbo is a member of the UNC
Lineberger Comprehensive Cancer Center.

Redinbo and his colleagues have filed a patent and formed a small
company to further develop the technology.

The study appears online the week of July 9, 2007, in the Proceedings
of the National Academy of Sciences. Funding was provided by the
National Institutes of Health.

Note: This story has been adapted from a news release issued by
University of North Carolina at Chapel Hill.