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#: 760146 S8/Complications  (CIS:DIABETES) 10-Oct-97  03:50:10 Sb: Bladder
	Bacteria Trick Fm: SYSOP-Curtise McKenzie 71172,2135 To: all Replies: 0
	TID: 107905    Par: 0         Chd: 0         Sib: 0






Bladder Bacteria Trick Revealed

By Leslie Lang

NEW YORK, Oct 09 (Reuters) -- Scientists have discovered that E. coli bacteria
can dodge antibiotics by hiding in the very immune system cells that would
normally engulf and destroy them.

The new findings may help explain why certain bacterial infections, including
bladder infections, keep coming back, even after treatment with antibiotics.

In a report published this week in the journal Nature, researchers at
Washington University School of Medicine in St. Louis, Missouri, describe how
E. coli -- the most abundant microbe in the human body -- uses a protein key
to unlock the door to macrophages, immune system cells that normally engulf
bacteria that become covered with antibodies produced by the body.

"When our bodies produce antibodies and other small proteins that bind to
bacteria, an immune cell such as a macrophage will recognize the protein, the
antibody. When that occurs, it engulfs the organism and shunts it down the
killing pathway," explains study lead-author Dr. David Baorto, a postdoctoral
researcher in the school's division of laboratory medicine.

"We have shown that a common organism can be taken into macrophages in other
than this classical pathway without getting killed," he says.

According to Baorto, the key to this bacterial trick is a protein called FimH,
"which is a sticky molecule that allows it to bind to a certain part on our
cells." The protein is located at the very tip of the bacterium's hair-like
structures, called pili. "It actually is the functional binding protein of the
pili," the researcher adds.

"We now know what the 'lock' is on our cells that the 'key' is binding to,"
Baorto says -- a particular protein on the macrophage's surface called CD48.
Once attached, E. coli slips into the cell and becomes safe from many
antibiotics -- including antibiotics such as gentamicin which kill microbes
directly and are not active within cells, Baorto explains.

"In cases where bacteria take advantage of this mechanism to enter cells, they
can later come out and reinfect," he adds.

                                        In the study, the researchers allowed
										macrophages to invade laboratory
										cultures of mouse macrophages. Baorto
										and his colleagues then bathed the
										cells in the antibiotic gentamicin.
										Microbes outside the cell were quickly
										destroyed. But those that got inside
										the macrophages by binding to CD48
										with the FimH protein survived the
										four-day experiment.

"Gentamicin is an antibiotic which does not penetrate cell membranes -- it
only works outside the cell. And by killing all the bacteria that were not yet
taken in, we used it as a tool to just follow how the macrophages handled the
bugs," the researcher says.

Areas of the body where E. coli is most likely to apply this FimH-CD48
interaction are those that have limited antibody activity, Baorto explains. He
says the walls of the bladder are one of these areas, theoretically, because
"the urine constantly washing through the bladder does not give antibodies the
opportunity to concentrate there."

The researcher also points out that bacterial invasion of macrophages in many
parts of the body may be more likely to occur "in people who are
immunocompromised so severely that they have deficiency in antibody
production." These people, he notes, would include those infected with HIV, a
group prone to recurrent, opportunistic infections.

SOURCE: Nature (1997;389:636-639)