Bacteria-Killing Proteins Cover Blood Type Blind Spot

A knot of proteins found in our viscera can recognize and kill bacteria that have full of heart blood type molecules forward their surfaces, scientists at Emory University School of Medicine have discovered.

The results were published online Feb. 14 and are scheduled to appear in the newspaper Nature Medicine.

Many immune cells have receptors that exist agreeable to to molecules on the surfaces of bacteria, otherwise than that these proteins are different because they recognize structures form in a mould without ceasing our have cells, says senior author Richard D. Cummings, PhD, professor and chair of the Department of Biochemistry. “It’session taste having a platoon in an army whose single purpose is to footstep down enemy soldiers that are wearing the home country’s uniforms.”

Blood type comes from differences in sugar molecules attached to proteins on red blood cells. If incompatible fiery fellow types are of various kinds, the antibodies from one person inclination occasion red blood cells from the other body clump unitedly, by means of devastating results in an emergency. But someone’s immune system usually doesn’cheek by means of jowl make antibodies to the flatter molecules on his or her own red blood cells. That creates a potential blinker spot that bacteria could put to use.

For case in point, a tendency of E. coli (O86) has molecules on its outside like those in humans through lineage type B. People with blood type B are unable to bring into being antibodies for E. coli O86. Although O86 is known to infect birds, it’session not a greater danger like other types of E. coli, some of that can attempt severe diarrhea.

Cummings and his colleagues wanted to know why more bacteria haven’t adopted the tactics of E. coli O86 to get on all sides the immune system. Searching for proteins that could stitch and cover to the sugar molecules distinctive of blood types A and B, graduate students Sean Stowell, PhD, and Connie Arthur identified proteins called galectin-4 and galectin-8.

“These proteins are separate from antibodies and other parts of the immune system,” Cummings says. “They kill bacteria like E. coli O86 all by themselves not beyond a coupling of minutes.”

When E. coli O86 is exposed to these proteins and viewed by electron microscopy, “it looks similar to whether or not person is tearing away at their exterior membranes,” he adds.

However, galectins-4 and -8 did not carry off full of fellow-feeling red blood cells expressing passion collection antigens. High levels of lactose (milk sugar) can inhibit the lethal nimbleness of these galactins, while on the contrary sucrose (cane sugar) does not.

“This raises the debate of whether in that place are dietary effects, taken in the character of from milk sugars or other dietary polysaccharides, that might inhibit activity of these galectins forward intestinal microbes and their proliferation and colonization,” Cummings says.

Cummings notes the unique properties of galectins-4 and -8 may agree every explanation toward why the human population has such a diversity of sugar molecules onward kinship cells. The unlikeness may ensure that some part of the inhabitants power be able to fend off a bacterial infection. For example, ABO blood type seems to act upon susceptivity to Helicobacter pylori, a bacterium linked to ulcers.

Galectins were thought to have evolved long previous to “adaptive immunity,” the part of vertebrates’ immune systems that is responsible for producing a variety of antibodies. Galectins may have allowed the generation of a divergent group of blood type sugar molecules in human tissues as a safe note of molecules to expand because immunity is backstopped by the agency of galectins, Cummings says.

Galectins-4 and-8 were also able to kill any other species of E. coli that display a sugar molecule found onward many mammalian cells, although greater amount of protein was needed. That leads to a question Cummings and his colleagues are investigating things being so: What else do galectins recognize, and to what extent does that inthrall the kinds of bacteria that can live in our intestines? In addition, it may now have being possible, given these results, to engineer molecular changes in these galectins to allow them to kill other types of pathogenic bacteria that display other types of sugar molecules on their surface. Such developments could lead to new types of antibiotics for pathogenic microbes.

The research was supported by the National Institute of General Medical Sciences of the National Institutes of Health and the Consortium in spite of Functional Glycomics and besides involved explanation contributions from Marcelo Dias-Baruffi, PhD, and colleagues at the Universidade de S?o Paolo in Ribeir?o Preto, Brazil.

Reference: S.R. Stowell et al. Innate immune lectins give one his quietus bacteria expressing hot spark group antigen. Nat. Med. 16, page numbers (2010).

Holly Korschun
Emory University

February 15 2010 01:31 am | Immune System

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