Researchers Identify Genetic Factors Enabling Deadly E. coli Strains to Infect

Researchers from Tokyo Metropolitan University have identified how certain dangerous bacteria are spread. They studied chain-like adherence pattern (CLAP) varieties of Shiga toxin-producing E. coli (STEC), finding that single bacteria attach to a surface and elongate before dividing, producing chains without ever separating. Under flow, chain ends which are torn off can attach elsewhere, dispersing the strain. They identified a new gene family mediating CLAP formation, illuminating new aspects of infection mechanisms and potential treatments.

Shiga toxin-producing Escherichia coli (STEC) are harmful bacteria responsible for serious mass food poisoning events, with a particular risk of severe disease and death in young children and the elderly. Most strains feature the locus of enterocyte effacement (LEE) within their genome, giving bacteria the ability to create lesions in the intestinal tract which help them attach and grow. While this is a major pathway by which STEC strains infect a host, LEE-negative strains, which have also been discovered, can be just as deadly, as demonstrated in a 2011 outbreak in Germany with the STEC strain O104:H4. Since they lack the molecular machinery conferred by LEE, scientists are yet to fully understand how these strains cause infection and spread.

To tackle this challenge, a team in Tokyo Metropolitan University led by doctoral candidate Yuto Kotaka are studying chain-like adherence pattern (CLAP) varieties of LEE-negative STEC strains. In O91, a frequently isolated LEE-negative strain in Japan, the European Union, and the United Kingdom, it was found that bacteria form threads or chains, but the way in which they are formed, and how they are dispersed, was not understood.

In recent work, the team observed how these chains were formed under the microscope. Instead of aggregating bacteria, they found that single bacteria could attach to a surface, elongate, then divide without individual bacteria ever being separated. Crucially, they found that environmental factors which might prevent bacteria developing a foothold, like a strong flow, could be used by the bacteria to disperse. For chains under flow, the team saw that the ends of a thread are torn off while leaving part of the original chain intact.

This separated segment is carried off downstream, where it can attach to a surface again and continue to grow. Thus, flow can form part of the strain's surface colonization strategy over wider areas. Watch the video of the bacterial chain dispersing: https://youtu.be/AU5UZ7PZYG4

To study the genetic factors essential for CLAP phenotypes, the team undertook a wide-ranging study of CLAP strains isolated in Japan. In analyzing the genes encoding for the EibG protein, an "adhesin" responsible for bacterial attachment to cells, they discovered a whole new branch of genes in CLAP forming STEC strains, the Cla adhesin family, whose knockout in experiments resulted in the complete disappearance of CLAP formations.

Uncovering the mechanisms by which deadly pathogens attach and develop within hosts is a vital step in understanding how they spread. This is a big step forward for understanding the behavior of LEE-negative bacteria, and how infections might be treated in the future.