New approach to treating infectious diseases as an alternative to antibiotics

July 11, 2018, Osaka University
New approach to treating infectious diseases as an alternative to antibiotics
Fig. 1. The mechanism of initial attachment of ETEC to human intestinal epithelium and its inhibition by antibodies. Credit: Osaka University

Osaka University-led researchers clarified how pathogenic E. coli bacteria attached to the host intestinal epithelium. They revealed that type IV pili on the surface of the bacteria were not sufficient for adherence to intestinal epithelial cells and that proteins secreted by E.coli were also necessary. It was found that this attachment mechanism might be a common feature in many enteropathogens such as Vibrio cholera and constitutes a novel therapeutic target against such bacterial pathogens.

Enterotoxigenic Escherichia coli (ETEC) is known as a major cause of diarrhea in travelers and people living in developing countries. According to the World Health Organization (WHO), ETEC is responsible for 300,000 ~ 500,000 deaths a year, constituting a serious problem.

Effective vaccines for ETEC have not been developed, so patients infected with ETEC are treated with antibiotics and supporting measures. However, the emergence of multidrug-resistant bacteria has become a social issue, so the development of new treatment methods is sought after.

Adherence to the host intestinal epithelium is an essential step for ETEC infection in humans. It was thought that a filamentous structure on the surface of bacteria called 'type IV pilus' was important for bacterial attachment, but its detailed adhesion mechanism was not known.

Osaka University-led researchers clarified how pathogenic E.coli attached to the host intestinal epithelium using type IV pili and secreted proteins. Their research results were published in PNAS.

Fig. 2. Structural model of the secreted protein CofJ (yellow) and CFA/III pilus complex. Credit: Osaka University

One of the corresponding authors, Shota Nakamura, says, "We demonstrated that type IV pili on the surface of the bacteria were not sufficient for ETEC adherence to intestinal epithelial cells and that proteins secreted by E.coli were also necessary. The administration of antibodies against the secreted proteins inhibited attachment of the E.coli."

Using X-ray crystallography, the researchers studied how a protein located only at the pilus-tip interacts with a secreted by E.coli in the intestines (Figure 2), clarifying the attachment mechanism of ETEC; that is, secreted proteins serve as molecular bridges that bind both type IV pili on the surface of the bacteria and in humans.

Nakamura also says, "It's possible that this attachment is a common feature in many type IV pili expressing enteropathogens such as Vibrio cholerae and constitutes a new therapeutic target against such bacterial pathogens."

Their research results will lead to the development of not only new vaccines for ETEC, but also anti-adhesion agents for preventing the binding of proteins implicated in bacterial . Anti-adhesion agents can rinse pathogenic bacteria out from the body without destroying them, so there is no danger of producing drug-resistant . These agents, once developed, will act as a novel treatment approach that may serve as an alternative to antibiotics.

Explore further: Molecular basis for varied presentations of ETEC explored

More information: Hiroya Oki et al. Interplay of a secreted protein with type IVb pilus for efficient enterotoxigenic Escherichia colicolonization, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073/pnas.1805671115

Related Stories

Molecular basis for varied presentations of ETEC explored

May 21, 2018

(HealthDay)—The EtpA adhesion molecule, which is secreted by enterotoxigenic Escherichia coli (ETEC) strain H10407, is a dominant ETEC blood group A-specific lectin/hemagglutinin, according to a study published online May ...

Researchers find new strategy to combat bacterial infections

January 29, 2014

Increasing numbers of bacteria are developing antibiotic resistance. This forms a significant challenge in the battle against bacterial infections. Alvin Lo and Han Remaut (VIB/Vrije Universiteit Brussel) have identified ...

New strategy to combat cystitis

June 3, 2011

One in three women will be faced at least once in her life with cystitis, for some the start of a constantly recurring infection. Cystitis is caused by Escherichia coli bacteria which fasten on to the wall of the bladder ...

Recommended for you

How quinoa plants shed excess salt and thrive in saline soils

September 21, 2018

Barely heard of a couple of years ago, quinoa today is common on European supermarket shelves. The hardy plant thrives even in saline soils. Researchers from the University of Würzburg have now determined how the plant gets ...

Basking sharks can jump as high and as fast as great whites

September 20, 2018

A collaborative team of marine biologists has discovered that basking sharks, hundreds of which are found off the shores of Ireland, Cornwall, the Isle of Man and Scotland, can jump as fast and as high out of the water as ...

Decoding the structure of an RNA-based CRISPR system

September 20, 2018

Over the past several years, CRISPR-Cas9 has moved beyond the lab bench and into the public zeitgeist. This gene-editing tool CRISPR-Cas9 holds promise for correcting defects inside individual cells and potentially healing ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.