Stomach cancer, Ku-fever, Legionnaire disease, donkey cough – Although the infectious bacteria that cause these dangerous diseases are different, they all use the same molecular technique to infect human cells. Bacteria use this machine called the Type IV (T4SS) secretion system to inject toxic molecules into cells and spread genes for antibiotic resistance to other bacteria. Now researchers at Caltech have unveiled the 3-D molecular architecture of T4SS from the human pathogen Legionella pneumophila with unprecedented details. This could in the future allow the development of targeted antibiotics for the above-mentioned diseases.
The work was done in the laboratory of Grant Jensen, a professor of biophysics and biology, and a researcher at the Howard Hughes Medical Institute, in collaboration with Joseph Vogel's laboratory at WUSTL, Washington University of Medicine. A paper describing the study appeared online on April 22 in the journal Nature Microbiology,
There are nine different types of bacterial secretion systems, Type IV is the most complex and flexible. T4SS can carry a wide variety of toxic molecules – up to 300 at a time – from bacteria in their cell sacrifice, abducting cellular functions and overwhelming cellular protective powers.
In 2017, Caltech's post-doctor Debnath Ghosal and his associates used a technique called electronic cryotography to first reveal the general T4SS low resolution architecture in Legionella, the bacterium that causes Legionnaires' disease, severe and often deadly. form of pneumonia.
Ghosal, along with Kwangcheol Jeong of WUSTL and their colleagues, have already made a detailed structural model of this dynamic multi-component machine. The team also made accurate bacterial genome disturbances to explore the mutant versions of T4SS, revealing how this complex machine organizes and assembles.
The model revealed that the secretory system consists of a separate chamber and a long channel, such as the chamber and the barrel of the gun. Characterization of these and other T4SS components may allow the development of targeted antibiotics.
Current antibiotics act extensively and destroy the bacteria in the body, including the beneficial microorganisms that live in our intestines. In the future, antibiotics may be designed to block only toxin delivery systems (such as T4SS) of harmful pathogens, which makes the bacteria inert and harmless without disturbing the so-called "
The article is entitled "Molecular architecture, polar orientation and biogenesis of Legionella Dot / Icm T4SS."
A 3-D image of a bacterial machine that injects toxins into the cells and spreads resistance to antibiotics
Debnath Ghosal et al., Molecular architecture, polar orientation and biogenesis of Legionella Dot / Icm T4SS, Nature Microbiology (2019). DOI: 10.1038 / s41564-019-0427-4
Dangerous pathogens use this sophisticated technique to infect hosts (2019, 17 May)
drawn on 18 May 2019
This document is subject to copyright. Apart from any honest work for the purposes of private research or research, no
may be reproduced without written permission. Content is provided for information purposes only.