Virulence Factor Building Block Found Hiding In Plain Sight

The discovery of the PATR motif found in the virulence factors of many harmful bacteria could lead to the development of new broad spectrum antibiotics.

AsianScientist (May 12, 2015) – Researchers have discovered a target for the development of completely new antibiotics against disease-causing bacteria.

Published online ahead of print in the leading microbiology journal Molecular Microbiology, the researchers from the University of Adelaide have identified a building block common to many types of bacterial ‘virulence factors,’ the bacterial proteins which act as weapons to cause disease, such as toxins or degrading enzymes.

The building block, called the passenger-associated transport repeat (PATR), has been found in virulence factors of many major harmful bacteria including Salmonella, Shigella and Meningococcus as well as bacteria that cause infections in cystic fibrosis and burns patients. It has been found in many of the major so-called ‘Gram negative bacteria,’ including those that have developed resistance to a broad range of antibiotics.

The PATR was shown to be integral in the transport of the virulence factors to the surface of the bacterial cell, where they need to be to function as disease-causing agents.

“Bacteria can only cause disease when virulence factors are appropriately produced by the bacteria and transported (or secreted) onto the cell surface where they become harmful,” says first author Mr. Matthew Doyle, PhD candidate in the School of Biological Sciences.

Commenting on their findings, Doyle elaborated on how this study contributes to the field.

“Our results are very exciting—we are not just talking about one molecule in one particular pathogen but rather a building block which is shared by thousands of common virulence factors produced by many major pathogenic bacteria. The PATR is crucial for those virulence factors to mature appropriately.

“It opens up the possibility for development of a completely new class of broad-spectrum bacterial virulence inhibitors. If we can inhibit this building block, we are really onto something.”

The discovery will also be useful in the biotechnology field for the development of a variety of marketable products and processes which rely on coupling biological molecules to cell surfaces.

The latest findings follow more than a decade of work led by Associate Professor Renato Morona looking at how bacteria cause disease. The research is expected to gain a lot of attention from the many groups around the world working in the field.

“We initially could not believe that this building block has been overlooked,” says Morona. “We’ve discovered something that’s been hidden in plain sight. It may shift the way research in this field is conducted.”

The article can be found at: Doyle et al. (2015) The Passenger-associated Transport Repeat Promotes Virulence Factor Secretion Efficiency And Delineates A Distinct Autotransporter Subtype.


Source: The University of Adelaide; Photo: NIAID/Flickr/CC.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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