Superbug impact on the gut

June 25, 2020

Monash University researchers have discovered that the devastating bacterial superbug Clostridioides difficile hijacks the human wound healing system in order to cause serious and persistent disease, opening up the development of new therapies to treat the disease.

Clostridioides difficile is the most common hospital-acquired disease and causes persistent and life-threatening gut infections - particularly in elderly and immunocompromised patients.

The infection is very difficult to treat, and often repeatedly reoccurs in patients even after they have been given powerful and debilitating antibiotics for many months. C. difficile is also highly resistant to antibiotics, which greatly complicates treatment.

A team based in the Monash Biomedicine Discovery Institute (BDI) found that C. difficile massively activates a human enzyme called plasminogen in order to destroy gut tissue and to help spread the infection throughout the patient. Ordinarily, plasminogen, and its active form plasmin, is deployed in a highly controlled fashion to break down scar tissue and help wounds heal.

"The results were a huge surprise, and revealed that the severe damage caused to the gut by C. difficile was actually caused by a human enzyme rather than a bacterial toxin," said study co-leader and infectious disease expert Prof Dena Lyras.

Given their findings, the researchers decided to investigate whether potent antibodies developed by the team and that inhibited the plasminogen / plasmin system could be used to treat the disease.

"We found that an antibody that prevented plasminogen from being activated dramatically stalled the progress of infection and tissue damage," said first author Milena Awad.

The researchers now aim to commercialise their antibodies in order to treat a range of bacterial and inflammatory diseases.

An advantage of targeting a human protein in an infectious disease is that resistance to the therapy is far less likely to occur.

"The antibody could have broad utility, since the plasminogen / plasmin system is dysregulated in a range of different serious inflammatory and infectious diseases - for example, the plasminogen system most likely is a driver of the devastating lung damage seen in COVID-19," said study co-leader and structural biologist Prof James Whisstock.
-end-
The study, published in the leading US journal Gastroenterology today, was led by senior authors Professor Dena Lyras, Dr Ruby Law and Professor James Whisstock, in conjunction with joint-lead authors Dr Milena Awad, Dr Melanie Hutton, and Dr Adam Quek.

Read the abstract of the paper in Gastroenterology titled: Human Plasminogen Exacerbates Clostridioides difficile Enteric Disease and Alters the Spore Surface

About the Monash Biomedicine Discovery Institute at Monash University

Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.

MEDIA ENQUIRIES

Media
Monash University
T: +61 3 9903 4840 E: media@monash.edu

Monash University

Related Antibiotics Articles from Brightsurf:

New tricks for old antibiotics
The study published in the journal Immunity reveals that tetracyclines (broad spectre antibiotics), by partially inhibiting cell mitochondria activity, induce a compensatory response on the organism that decreases tissue damage caused during infection.

Benefits, risks seen with antibiotics-first for appendicitis
Antibiotics are a good choice for some patients with appendicitis but not all, according to study results published today in the New England Journal of Medicine.

How antibiotics interact
Understanding bottleneck effects in the translation of bacterial proteins can lead to a more effective combination of antibiotics / study in 'Nature Communications'

Are antivitamins the new antibiotics?
Antibiotics are among the most important discoveries of modern medicine and have saved millions of lives since the discovery of penicillin almost 100 years ago.

Hygiene reduces the need for antibiotics by up to 30%
A new paper published in the American Journal of Infection Control (AJIC), finds improved everyday hygiene practices, such as hand-washing, reduces the risk of common infections by up to 50%, reducing the need for antibiotics, by up to 30%.

Antibiotics: City dwellers and children take the most
City dwellers take more antibiotics than people in rural areas; children and the elderly use them more often than middle-aged people; the use of antibiotics decreases as education increases, but only in rich countries: These are three of the more striking trends identified by researchers of the NRW Forschungskolleg ''One Health and Urban Transformation'' at the University of Bonn.

Metals could be the link to new antibiotics
Compounds containing metals could hold the key to the next generation of antibiotics to combat the growing threat of global antibiotic resistance.

Antibiotics from the sea
The team led by Prof. Christian Jogler of Friedrich Schiller University, Jena, has succeeded in cultivating several dozen marine bacteria in the laboratory -- bacteria that had previously been paid little attention.

Antibiotics not necessary for most toothaches, according to new ADA guideline
The American Dental Association (ADA) announced today a new guideline indicating that in most cases, antibiotics are not recommended for toothaches.

Antibiotics with novel mechanism of action discovered
Many life-threatening bacteria are becoming increasingly resistant to existing antibiotics.

Read More: Antibiotics News and Antibiotics Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.