Bacteria “drones” and IBD

BioMed Radio - Washington University School of Medicine in St. Louis

A newly discovered link between bacteria and immune cells may be a significant contributor to inflammatory bowel disease, according to researchers at Washington University School of Medicine in St. Louis.

SCIENTISTS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS AND THE UNIVERSITY OF MICHIGAN HAVE FOUND A NEW WAY THAT BACTERIA CAN INTERACT WITH A HOST�S IMMUNE CELLS. AND THE NEWLY DISCOVERED CONNECTION MAY BE A KEY FACTOR IN INFLAMMATORY BOWEL DISEASE. JIM DRYDEN REPORTS�

THE STUDY, IN MICE THAT DEVELOP A CONDITION SIMILAR TO VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE, OR IBD, HIGHLIGHTS A PROTEIN THAT COULD BE A POTENTIAL TARGET FOR NEW IBD TREATMENTS. THE RESEARCHERS KNEW THAT A SPECIFIC BACTERIUM, CALLED B THETA, WAS VERY GOOD AT TRIGGERING THE INFLAMMATION. BUT THE STUDY�S FIRST AUTHOR, CHRISTINA AHN-HICKEY, SAYS THEY DIDN�T KNOW EXACTLY WHERE THE B THETA SETTLED TO CAUSE THE PROBLEMS. SO FINDING THAT ANSWER WAS THE FIRST ORDER OF BUSINESS.

(act) :16 o/c that question

The broad idea in the literature was that bacteria
themselves got into the host tissue in the gut, and so
that was kind of where we started. We needed to find a
way to visualize the bacteria themselves to get at that
question.

THEY USED MICROSCOPY TO LOOK AT THE MUCUS LAYER OF THE INTESTINE. THEY ALSO USED MUTANTS OF THE B THETA BACTERIA TO SEE WHETHER ANY OF THEM COULD GET THROUGH THAT PROTECTIVE MUCUS LAYER IN THE GUT. AND FINALLY, THEY FOUND ANTIBODIES TO THE BACTERIA THAT COULD ALLOW THEM TO VISUALIZE WHAT WAS GOING ON MORE EASILY. ONE OF THE ANTIBODIES GAVE THEM A GOOD LOOK AT THE WHOLE B THETA BACTERIUM.

(act) :26 o/c other restrictions

The other seemed to target not so much the bacteria itself
but some sort of product of the bacteria, which we then
found through closer imaging that this was actually an
outer membrane vesicle. Bacteria release these vesicles �
we think of it as a �mothership� releasing �fighter jets.�
The fighter jets are able to get to places where the
mothership can�t go.

AHN-HICKEY SAYS THE VESICLES RELEASED BY THE �MOTHERSHIP� ARE WHAT INTERACT WITH THE IMMUNE CELLS FROM THE MICE TO CAUSE INFLAMMATION AND IBD.

(act) :10 o/c parent bug

These are the factors that cause colitis, not the parent
microbe getting into the tissue itself, but these
little vesicles that come off of the parent bug.

AND PRINCIPAL INVESTIGATOR THAD STAPPENBECK SAYS THE WAY THOSE PIECES OF BACTERIA CAUSE THE PROBLEMS IS BY CARRYING SPECIFIC ENZYMES AND PROTEINS INTO PLACES WHERE THE BACTERIA CAN�T GO.

(act) :24 o/c potentially can

B theta�s about a micron or so in largest dimension, but
these vesicles are on the order of 10 to 20 to 30 nanometers,
so they�re a couple of orders of magnitude smaller, which is
really important because these now fit through some of the
pores that are present in the mucus layer. The mucus layer
is actually this tight �lattice� that, actually, bacteria
can�t fit through. But these little, tiny vesicles potentially
can.

THE GOOD NEWS, STAPPENBECK SAYS, IS THAT THOSE TINY VESICLES MAY EVENTUALLY BECOME TARGETS FOR TREATMENT.

(act) :15 o/c the gut

You may even be able to deliver things in the intestine
specifically. Most therapies are systemically delivered.
Their delivered in the bloodstream, or they go everywhere.
If you could engineer a microbe to deliver these small
vesicles, this is something that could be specifically,
really, for the gut.

STAPPENBECK, AHN-HICKEY AND THEIR COLLEAGUES REPORT THEIR FINDINGS IN THE JOURNAL CELL HOST & MICROBE. I�M JIM DRYDEN…

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