By

M. Kulandhaivel

I M.Sc.,

Department of Biochemistry

Orcadian Population Investigating the Relationship between Human Plasma N-glycans and Metabolic Syndrome

Glycosylation refers to the enzymatic post-translational modification in which the addition of complex oligosaccharide molecules (glycans) enriches protein complexity and functional diversity. Glycans have a broad spectrum of biological roles, including their influence on protein folding, cell signaling and immune function. Alongside the genome and proteome, the human glycome is subject to immense variation.

Protein Markers Associated with an ALDH Sub-Population in Colorectal Cancer

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Although almost 70% of patients can be operated on with intent to cure, up to 30% of all these patients will relapse within 2-3 years. Survival rates for colon cancer have steadily improved mainly due to a combination of earlier diagnosis and improvements in treatment. Nevertheless, an improved understanding of the protein signaling pathways could provide new biomarkers for potential targets of therapeutic and surgical intervention.
By
Chandrasekaran
Final year biochemistry

University of California, Irvine and MIT researchers have developed a new strategy to immunize against microbes that invade the gastrointestinal tract, including Salmonella, which causes more foodborne illness in the United States than any other bacteria.

Source: University of California, Irvine

The researchers targeted a molecule that Salmonella and other bacteria secrete to scavenge iron, which is essential to many cellular functions. Immunization against this molecule led to the production of antibodies that reduced Salmonella growth, and to much lower levels of the bacteria. This approach could offer an alternative to antibiotics, which can cause side effects because they also kill beneficial bacteria. Using too many antibiotics can also lead to drug resistance. "Enteric infections are difficult to treat, because antibiotics also disrupt the body's beneficial microbes that can provide a defense against these pathogens," said Manuela Raffatellu, a UCI associate professor of microbiology & molecular genetics. "Our strategy is narrow-spectrum and augments the host's existing defenses." Raffatellu and MIT's Elizabeth Nolan are the senior authors of the study, which appears in the Proceedings of the National Academy of Sciences the week of Nov. 7. The paper's lead authors are Martina Sassone-Corsi, a UCI postdoctoral scholar, and Phoom Chairatana, who recently received a doctorate in chemistry at MIT.

Iron-clad defenses

Most bacteria, as well as some fungi, use molecules known as siderophores to obtain iron, a metal that is critical for cellular processes including metabolism and DNA synthesis. Bacteria that live in the intestinal tract secrete siderophores into the gut and then reabsorb them after they have grabbed onto iron. There are hundreds of different types of siderophores, and in this study, the researchers focused on a subset of siderophores that are produced by Salmonella and a few other types of pathogenic bacteria that can live in the gut. The researchers were inspired by the way that some organisms naturally combat microbes by blocking their iron uptake. Humans have a defense protein known as lipocalin 2, which can capture some siderophores and prevent these molecules from carrying iron into bacterial cells. However, lipocalin 2 is not effective against certain types of siderophores, including one type used by Salmonella. "There's no identified human defense mechanism against some of these molecules. That's how we got thinking about how we could boost this metal-withholding response via an immunization," Nolan said.

The siderophore molecules are too small to induce an immune response from a host organism, so the researchers decided to attach it to a protein that does induce an immune response -- cholera toxin subunit B (CTB). The siderophore-CTB complex is delivered nasally or injected into the abdomen and makes its way to the lining of the GI tract, where the body begins producing antibodies against both CTB and the siderophore. The researchers gave mice the immunization twice, two weeks apart, and then infected them with Salmonella 36 to 51 days after the first immunization. They found that antibodies against the siderophores peaked around 21 days after the first immunization and then remained at high levels. The immunized mice also had much smaller numbers of Salmonella in their gut and did not experience the weight loss seen in mice that were infected but not immunized. In a paper appearing in the same issue of PNAS, researchers at the University of Michigan used a similar approach to generate an immune response against E. coli that can cause urinary tract infections.

Bacterial benefits

The researchers also found that immunization not only reduced the Salmonella population but also led to the expansion of the population of a beneficial bacteria known as Lactobacillus -- the probiotic bacteria found in yogurt, which help to inhibit the growth of pathogenic microbes. "We think that the expansion of Lactobacillus may be conferring additional benefit to the host," Nolan says. This immunization strategy could be useful to protect people at high risk for certain kinds of infections, such as people who have compromised immune systems or cancer patients receiving chemotherapy, Nolan says. This approach could also be used to generate antibodies to treat people after they become infected with certain pathogens, such as Salmonella. The researchers are now working to isolate and analyze the antibodies that the mice produced in this study, and they are developing immunization strategies against other types of siderophores found in other organisms.

By

Dr. G. Saravanan

Associate Professor & Head

Department of Biochemistry

A team at Griffith's Institute for Glycomics identified a unique sensory structure that is able to bind host-specific sugar and is present on particularly virulent strains of Campylobacter jejuni.

Source:Griffith University

In their paper A direct-sensing galactose chemoreceptor recently evolved in invasive strains of Campylobacter jejuni published in Nature Communications this week, the team explain that the ability to cause disease depends on the ability of bacterial cells to move towards their target host cells. This movement is determined by specialised structures on the bacterial cells called sensory receptors that sense chemicals in their environment. It is the first known finding of a bacterial sensor that can bind sugar directly.

Campylobacter bacteria are now well recognised as one of the most common cause of food borne enteritis and have surpassed other food bugs such as Salmonella and Shigella as causes of illness, hospitalisation and of lost production in the workplace. The campylobacter infection is usually passed to humans from food animals, particularly poultry, through consumption of undercooked meats, unpasteurised milk and contaminated water. The researchers used chicken models to look at the mutant displays with disabled CcrG sensor and determined that disabling just this one sensor reduces the ability of campylobacteria to colonise chickens.

"This is a very important finding as sensory structures are very specific to each bacteria and offer high target specificity for design of new antimicrobial compounds," says research leader Professor Victoria Korolik. "Essentially it should be possible to design an antimicrobial drug to target a specific pathogen that will not affect normal flora." "Targeting sensory apparatus of microbes also reduces risk of development of antimicrobial resistance, since the bacterial cell will not be killed, but rather, have its ability to reach host cells and cause disease, disabled." "In addition, getting an understanding of how bacterial sensors bind to chemicals has enormous potential for the future. With understanding will come the ability to engineer bacteria with a set of sensors that will selectively direct cancer-killing bacteria toward cancer cells or direct bacteria that degrade chemicals in environmental contamination, such as oil spills to the contaminated areas."

By

V. V. SATHIBABU UDDANDRAO    

JRF & Ph. D Research Scholar

Department of Biochemistry