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Tuesday, March 29, 2005 Microbe Masquerade For the past couple of days, the blogosphere has been oohing and ahhing over the observations that octopuses can troll around the sea floor looking like coconuts and algae, but this is hardly unique in nature. Even seemingly "dumb" bacteria can don disguises and sneak right past watchful eyes. And they don't even have to go through the trouble of walking on two legs. A recent review in Science tells us that our gut contains up to 100 trillion microbes with genomic material that may exceed 100 times the number of our own genes. The most obvious benefit that these microbes have for their hosts is that of nutrition--they help break down food. But in order to stay in the nice comfortable niche of the GI tract, these microbes must develop some sort of strategy to evade the immune response in which the primarily response is to recognize self from non-self. So how to overcome this "immunological paradox"?  Another article in Science by Coyne et al. examines the gut bacterium Bacteroides fragilis and its particular strategy for immune evasion. A large percentage of our gut microflora consists of Bacteroides species--up to 30-50% of the feces--which are important energy sources for our colon cells by producing butyrate, acetate, and propionate. They're also important for creating a nonhospitable environment for pathogens like Salmonella although occasionally, B. fragilis can get out of control too and cause abdominal absesses and diarrhea.But what does B. fragilis get out of the whole deal? One can think of the bacteria as tiny herds of herbivores snipping off the sugar residues (fucose) on the surface of host cells and using those sugars for food. But how to evade those immune cells scouting for rogue bacteria? Coyne et al. teased apart the fucose metabolic pathway in B. fragilis and discovered that not only does the bacterium use the sugar as an energy source, but it also incorporates the sugar into the polysaccharides making up the bacterial capsule. So these bugs are not just eating the "grass" but are sticking clumps of vegetation onto their hides to escape the notice of the host's police force. This type of camouflage on the molecular scale is called molecular mimicry or "crypsis". This hypothesis proposes that molecular structures such as amino acid sequences and proteins with a specific conformation may be similar in two different organisms (like a microbe and its host), but the origin of those similar molecules are different. In 1964, R.T. Damian coined the term "molecular mimicry" to describe the idea that microbes evolved similar antigens to the host to evade immune response. But what happens when molecular mimicry "fails"? In the early 1980s researchers were attempting to generate monoclonal antibodies to the measles and herpes simplex viruses. When these antibodies were tested, some of them not only interacted with the virus proteins but also host "self" proteins such as the ones found on the surface of T cells. Later experiments with animal models proved that this phenomenon wasn't just a fluke and analysis of amino acid sequences showed that some viral proteins and self proteins have significant homology. This failure of molecular mimicry can spell disaster for ourselves, especially for people with hypervigilant immune systems (such as lacking T cell Robin Hoods). A major problem that molecular mimicry poses to our health is autoimmune disease. If a microbe cloaks itself in proteins or molecules that are similar to the ones host cells, the immune system can get confused and not only attack the microbes but also our own cells. But for our commensal microbes it's business as usual as they dispense nutrients in our guts with disguises intact. [posted by S. Y. Affolee on 3:53 AM : ]
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