Gastric cancer, Q fever, Legionnaire's disease, whooping cough – although the infectious bacteria that cause this dangerous disease vary, they all use the same molecular machinery to infect human cells. Bacteria use this machine, called the Type IV secretion system (T4SS), to inject toxic molecules into cells and also to spread genes for antibiotic resistance to fellow bacteria. Now, researchers at Caltech have revealed the 3-D molecular architecture of T4SS from the human pathogen Legionella pneumophila with unprecedented detail. This in the future allows the development of antibiotics that are well targeted for these diseases.
The work was carried out in the laboratory of Grant Jensen, professor of biophysics and biology and researcher at the Howard Hughes Medical Institute, working with the Joseph Vogel laboratory at the University of Washington Medical School in St. Louis. Louis (WUSTL). A paper describing the study appeared online on April 22 in the journal Natural Microbiology.
There are nine types of bacterial secretion systems, the most complicated and versatile Type IV. T4SS can transport various toxic molecules – up to 300 at a time – from bacteria into their cellular victims, hijack cellular functions and flood cell defenses.
In 2017, postdoctoral scholar Caltech Debnath Ghosal and colleagues used a technique called electron cryotomography to reveal, for the first time, the overall low resolution T4SS architecture in Legionella, the bacteria that causes Legionnaires disease, which is severe and often deadly forms of pneumonia.
The Ghosal, together with Kwangcheol Jeong from WUSTL and their colleagues, have now made a detailed structural model of this dynamic multi-component engine. The team also made a proper interference with the bacterial gene to study the mutant version of T4SS, revealing how this complex machine regulates and assembles.
The model reveals that the secretion system consists of different spaces and long channels, such as the space and barrel of a weapon. Characterizing this and other components of T4SS can enable the development of antibiotics that are right on target.
Antibiotics currently work extensively and destroy bacteria throughout the body, including beneficial microorganisms that live in our intestines. In the future, antibiotics can be designed to block only the toxin delivery system (such as T4SS) from harmful pathogens, making the bacteria inert and harmless without disturbing the so-called "good bacteria" in the body.
This paper is titled "Molecular architecture, targeting poles, and biogenesis of Legionella Dot / Icm T4SS."
3-D image of a bacterial machine that injects toxins into cells and spreads antibiotic resistance
Debnath Ghosal et al, Molecular architecture, targeting poles and biogenesis of Legionella Dot / Icm T4SS, Natural Microbiology (2019). DOI: 10.1038 / s41564-019-0427-4
Malicious pathogens use this sophisticated machine to infect hosts (2019, May 17)
taken May 18, 2019
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