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Dangerous pathogens infect with this sophisticated machinery host



  Dangerous pathogens infect with this sophisticated machinery host.
Photo credit: California Institute of Technology

Gastric cancer, Q fever, Legionnaire's disease, whooping cough ̵

1; although the infectious bacteria that cause these dangerous diseases are different, they all use the same molecular machinery to infect human cells. Bacteria use this machinery, called the Type IV secretion system (T4SS), to inject toxic molecules into cells and spread antibiotic resistance genes to other bacteria. Caltech researchers have now unveiled the T4SS 3-D molecular architecture of the human pathogen Legionella pneumophila with unprecedented detail. In the future, this could enable the development of targeted antibiotics against the diseases mentioned.

The work was carried out in the laboratory of Grant Jensen, Professor of Biophysics and Biology and researcher at the Howard Hughes Medical Institute, in collaboration with the laboratory of Joseph Vogel at the Washington University School of Medicine in St. Louis (WUSTL). An article describing the research appeared online on April 22 in the journal Nature Microbiology .

There are nine different types of bacterial secretion systems, with Type IV being the most sophisticated and versatile. A T4SS can carry a variety of toxic molecules – up to 300 simultaneously – from a bacterium into its cellular victim, steal cellular functions, and overwhelm cell defenses.

In 2017, Caltech postdoctoral fellow Debnath Ghosal and his associates used a technique called electron cryotomography, which first unveils the low-resolution T4SS overall architecture in Legionella, a bacterium that causes Legionnaires' Disease, a serious and often deadly form of pneumonia ,

Ghosal and Kwangcheol Jeong of WUSTL and their colleagues have now created a detailed structural model of this dynamic multi-component machine. The team has also precisely disturbed the genes of the bacterium to study mutated versions of the T4SS and uncover how this complex machine organizes and assembles.

<img src = "https://3c1703fe8d.site.internapcdn.net/newman/csz/news/800/2019/dangerouspat.gif" alt = "Dangerous pathogens use this sophisticated machinery to infect hosts The Type IV secretion system shows how this complex bacterial machine is composed Picture credits: Jensen Labor

The model revealed that the secretion system, like the chamber and the barrel of a weapon, consists of a separate chamber and a long channel. The characterization of these and other components of T4SS could allow the development of targeted antibiotics.

Current antibiotics work to a great extent and eliminate bacteria throughout the body, including the beneficial microorganisms that live in our intestines. In the future, antibiotics could be developed to block only the toxin delivery systems (such as the T4SS) of harmful pathogens and render the bacteria inert and harmless without disturbing the body's so-called "good bacteria".

"Molecular architecture, polar targeting and biogenesis of the Legionella Dot / Icm T4SS."


3-D image of a bacteria machine that injects toxins into cells and spreads antibiotic resistance


Further information:
Debnath Ghosal et al., Molecular Architecture, Polar Targeting and Biogenesis of the Legionella Dot / Icm T4SS, Nature Microbiology (2019). DOI: 10.1038 / s41564-019-0427-4

Provided by
California Institute of Technology




Quote :
Dangerous pathogens infect with these sophisticated machinery hosts (2019, May 17)
retrieved on May 18, 2019
from https://phys.org/news/2019-05-dangerous-pathogens-sophisticated-machinery-infect.html

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