By Emily Caldwell
Scientists have combined chemistry and biology research techniques to explain how certain bacteria grow structures on their surfaces that allow them to simultaneously cause illness and protect themselves from the body’s defenses.
The researchers are the first to reproduce a specific component of this natural process in a test tube – an essential step to fully understanding how these structures grow.
With the new method described, these and other researchers now can delve even deeper into the various interactions that must occur for these structures – called lipopolysaccharides – to form, potentially discovering new antibiotic targets along the way.
Lipopolysaccharides are composed primarily of polysaccharides – strings of sugars that are attached to bacterial cell surfaces. They help bacteria hide from the immune system and also serve as identifiers of a given type of bacteria, making them attractive targets for drugs. But before a drug can be designed to inhibit their growth, scientists must first understand how polysaccharides are developed in the first place.
Now that scientists can reproduce formation of the lipopolysaccharide, they can more directly characterize the export process – a step in the pathway that serves as another potential antibiotic target
“We were able to answer some of the questions about how components of this growth system do their jobs. This will allow us to more fully characterize lipopolysaccharide biosynthesis in vitro, a process which may shed light on useful targets for developing antibiotic agents,” said Robert Woodward, a graduate student in chemistry at Ohio State University and lead author of the study.
The study is published in the April 25 online edition of the journal Nature Chemical Biology.
The researchers used a harmless strain of Escherichia coli as a model for this work, which would apply to other E. coli strains and similar Gram-negative bacteria, a reference to how their cell walls are structured.
The surface of these bacteria house the lipopolysaccharide, which is a three-part molecular structure embedded into the cell membrane. Two sections of this structure are well understood, but the third, called the O-polysaccharide, has to date been impossible to reproduce.
Two significant challenges have hindered research efforts in this area: The five sugars strung together to compose this section of the molecule are difficult to chemically prepare in the lab, and one of the key enzymes that initiates the structure’s growth process doesn’t easily function in a water-based solution in a test tube.
Ohio State synthetic chemists and biochemists put their heads together to solve these two problems, Woodward said.
To produce the five-sugar chain, the researchers started with a chemically prepared building block containing a single sugar and introduced enzymes that generated a five-sugar unit from that single carbohydrate.
“The first part was done chemically, and in the second part, we used the exact same enzymes that are normally present in a bacterial cell to transform the single sugar into a five-sugar string,” Woodward said.
