Special Proteins Guide Immunity Against Bacteria that Employ 'Glycan Camouflage'

Our bodies produce a family of proteins that recognize and kill bacteria whose carbohydrate coatings are similar but not identical to those of our own cells, scientists at The Scripps Research Institute (TSRI) and Emory University School of Medicine have discovered.

Called galectins, these proteins recognize carbohydrates from a broad range of disease-causing bacteria and could potentially be deployed as antibiotics to treat certain infections.  

The results were published online ahead of print on May 11, 2014 by the journal Nature Chemical Biology.

The team made the discovery with the aid of glass slides coated with an array of glycans (carbohydrates found on the surfaces of cells) derived from more than 300 species of bacteria, many of which are found in the intestine. One can think of the library of glycans on these slides—called microbial glycan microarrays—as wardrobes displaying a variety of clothes worn by gut bacteria.

“Our contribution was the production of this expanded microbial glycan array,” said James Paulson, chair of the TSRI Department of Cell and Molecular Biology, who led the research with Richard D. Cummings, professor and chair of the Department of Biochemistry at Emory. “This new array will place TSRI as a leader, if not the leader, in developing glycan array tools accessible to the scientific community.”

TSRI is already known worldwide for glycan arrays, producing the largest mammalian glycan microarray. Data from this array has been used in hundreds of publications by investigators that gain access through the Consortium for Functional Glycomics.

In this recent report, the team used the new bacterial glycan array to understand the ways in which adaptive or antibody-based factors work together with innate or galectin-based immune factors to give us protection against a broad range of microbes. To prevent autoimmune attack, our bodies usually don’t make antibodies against molecules found on our own cells. That leaves gaps in our defenses that bacteria could exploit. Several of those gaps are filled by galectins, the researchers found.

The discovery expands upon an initial finding, published in Nature Medicine in 2010, describing galectins that recognize and kill bacteria that express the human blood group B antigen.

In contrast to antibodies, the galectins kill the bacteria directly, without needing other parts of the immune system to pile on. The researchers identified several varieties of bacteria (Pseudomonas aeruginosa, Providencia alcalifaciens, Klebsiella pneumoniae and Serratia marcescens, for example) targeted for killing by galectins. In some cases, only certain strains of a given bacteria were vulnerable, because only those strains carried the target glycan.

The new microarray technology opens up many potentially productive avenues of research, the authors say.

“Using these tools, investigators could identify developmental- and age-specific differences in antimicrobial glycan antibodies in humans, which may predict susceptibility to disease,” Cummings said. “These studies use tiny amounts of blood—just a few drops—and show how glycan microarrays could supersede previous technology.”

Co-first authors of the paper “Microbial glycan microarrays define key features of host-microbial interactions” are Ryan McBride, research assistant at TSRI; Sean Stowell, a resident in laboratory and transfusion medicine at Emory; and Connie Arthur, postdoctoral fellow at Emory.

Other authors include Oren Berger and Nahid Razi of TSRI; Jamie Heimburg-Molinaro, Lilian C Rodrigues, Jean-Philippe Gourdine, Alexander J. Noll and David F Smith of Emory University School of Medicine; Stephan von Gunten of University of Bern (Bern, Switzerland); and Yuriy A Knirel of Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences (Moscow). See http://www.nature.com/nchembio/journal/vaop/ncurrent/abs/nchembio.1525.html

The research was supported by the National Institute of Allergy and Infectious Diseases (AI050143), the National Heart Lung and Blood Institute (HL107151, HL085607), the National Institute for General Medical Sciences (GM103694, GM098791, GM62116), the US National Blood Foundation, the Swiss National Science Foundation, CSL Behring AG and the Brazilian Ministry of Education.

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