Bacteria-killing proteins cover blood type blind spot

Feb 14, 2010

A set of proteins found in our intestines can recognize and kill bacteria that have human blood type molecules on 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 journal Nature Medicine.

Many have receptors that respond to molecules on the surfaces of bacteria, but these proteins are different because they recognize structures found on our own cells, says senior author Richard D. Cummings, PhD, professor and chair of the Department of Biochemistry. "It's like having a platoon in an army whose sole purpose is to track down enemy soldiers that are wearing the home country's uniforms."

comes from differences in sugar molecules attached to proteins on . If incompatible blood types are mixed, the antibodies from one person will make red blood cells from the other person clump together, with devastating results in an emergency. But someone's usually doesn't make antibodies to the sugar molecules on his or her own red blood cells. That creates a potential blind spot that bacteria could exploit.

For example, a strain of E. coli (O86) has molecules on its surface like those in humans with blood type B. People with blood type B are unable to produce antibodies against E. coli O86. Although O86 is known to infect birds, it's not a major danger like other types of E. coli, some of which can cause severe diarrhea.

Cummings and his colleagues wanted to know why more bacteria haven't adopted the tactics of E. coli O86 to get around the immune system. Searching for proteins that could bind to the sugar molecules characteristic 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 within a couple of minutes."

When E. coli O86 is exposed to these proteins and viewed by electron microscopy, "it looks as if somebody is tearing away at their outer membranes," he adds.

However, galectins-4 and -8 did not kill human red blood cells expressing blood group antigens. High levels of lactose (milk sugar) can inhibit the lethal activity of these galactins, whereas sucrose (cane sugar) does not.

"This raises the question of whether there are dietary effects, as from milk sugars or other dietary polysaccharides, that might inhibit activity of these galectins on intestinal microbes and their proliferation and colonization," Cummings says.

Cummings notes the unique properties of galectins-4 and -8 may provide an explanation for why the human population has such a diversity of sugar molecules on blood cells. The diversity may ensure that some part of the population might be able to fend off a bacterial infection. For example, ABO blood type seems to affect susceptibility to Helicobacter pylori, a bacterium linked to ulcers.

Galectins were thought to have evolved long before "adaptive immunity," the part of vertebrates' immune systems that is responsible for producing a variety of . Galectins may have allowed the generation of a diverse group of blood type sugar molecules in human tissues as a safe set of molecules to evolve because immunity is backstopped by galectins, Cummings says.

Galectins-4 and-8 were also able to kill another variety of E. coli that display a found on many mammalian cells, although more protein was needed. That leads to a question Cummings and his colleagues are investigating now: What else do galectins recognize, and how does that constrain the kinds of bacteria that can live in our intestines? In addition, it may now be 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.

Explore further: New malaria vaccine candidates identified

More information: S.R. Stowell et al. Innate immune lectins kill bacteria expressing blood group antigen. Nat. Med. 16, (2010).

Related Stories

Swiss researchers develop antibody test

Mar 03, 2008

ETH Zurich professor Peter Seeberger has been working on a sugar-based malaria vaccine for years. The new test takes him one important step closer to his goal. The malaria pathogen plasmodium falciparum carries poisonous ...

Cancer-fighting antibodies

Dec 22, 2008

(PhysOrg.com) -- MIT engineers have found that antibodies do not need a particular sugar attachment long believed to be essential to their function, a discovery that could make producing therapeutic antibodies ...

Going from ulcers to cancer

Aug 22, 2008

Researchers have uncovered a big clue as to why some of the bacteria that cause stomach ulcers pose a greater risk for serious problems like stomach cancer than others; it turns out these bacteria can exploit the surrounding ...

White blood cells are picky about sugar

Jul 11, 2007

Biology textbooks are blunt—neutrophils are mindless killers. These white blood cells patrol the body and guard against infection by bacteria and fungi, identifying and destroying any invaders that cross ...

Recommended for you

Breakthrough in understanding of important blood protein

52 minutes ago

The human body contains a unique protein that has the unusual property of destroying itself after a few hours of existence - it must therefore be continually recreated and is no stable protein. The protein, ...

Key to aging immune system is discovered

1 hour ago

There's a good reason people over 60 are not donor candidates for bone marrow transplantation. The immune system ages and weakens with time, making the elderly prone to life-threatening infection and other ...

Putting a number on pain

1 hour ago

"How much pain are you in?" It's a harder question than many people think. Tools for assessing patients' pain—be they children or adults—rely on perception: a subjective measure that eludes quantification ...

New infections cause dormant viruses to reactivate

2 hours ago

The famous slogan is "A diamond is forever," but that phrase might be better suited to herpes: Unlike most viruses, which succumb to the immune system's attack, herpes remains in the body forever, lying in wait, sometimes ...

User comments : 0