Revealing how an adenylate cyclase toxin uses bait and switch tactics in its activation

PLoS Biology
Natosha L Finley

Abstract

Dissecting how bacterial pathogens escape immune destruction and cause respiratory infections in humans is a work in progress. One tactic employed by microbes is to use bacterial adenylate cyclase toxins (ACTs) to disarm immune cells and disrupt cellular signaling in host cells, which facilitates the infection process. Several clinically significant pathogens, such as Bacillus anthracis and Bordetella pertussis, have ACTs that are stimulated by an activator protein in human cells. Research has shown that these bacterial ACTs have evolved distinct ways of controlling their activities, but our understanding of how the B. pertussis ACT does this is limited. In a recent study, O'Brien and colleagues provide new and exciting evidence demonstrating that the regulation of B. pertussis ACT involves conformational switching between flexible and rigid states, which is triggered upon binding the host activator protein. This study increases our knowledge of how bacterial ACTs are unique enzymes, representing a potentially novel class of drug targets that may open new pathways to combat reemerging infectious diseases.

References

Dec 1, 1989·Infection and Immunity·A A Weiss, M S Goodwin
Jul 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·J WolffS A Berkowitz
Apr 28, 1999·Trends in Microbiology·D Ladant, A Ullmann
May 2, 2003·The Journal of Biological Chemistry·Tobias S UlmerAd Bax
Nov 22, 2011·Journal of Molecular Biology·Julie Rumi-MasanteTrevor P Creamer
May 27, 2014·Journal of Molecular Biology·Alvaro VillarroelPilar Areso
Jun 8, 2014·The Journal of Biological Chemistry·Edithe SelwaThérèse E Malliavin
Sep 25, 2014·Biochemical and Biophysical Research Communications·Tzvia I SpringerNatosha L Finley
Dec 30, 2017·PLoS Biology·Darragh P O'BrienAlexandre Chenal

❮ Previous
Next ❯

Citations

Apr 8, 2020·Toxins·Rudolf LucasJürg Hamacher
Jun 12, 2020·Journal of Pharmaceutical and Biomedical Analysis·Lisa SzymkowiczD Andrew James

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthrax Vaccines

Three different types of anthrax vaccines are available; a live-attenuated, an alum-precipitated cell-free filtrate and a protein recombinant vaccine. The effectiveness between the three is uncertain, but the live-attenuated have shown to reduce the risk of anthrax with low adverse events. Here is the latest research on anthrax vaccines.

Anthrax

Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Here is the latest research on Anthrax.

Anthrax Vaccines (ASM)

Three different types of anthrax vaccines are available; a live-attenuated, an alum-precipitated cell-free filtrate and a protein recombinant vaccine. The effectiveness between the three is uncertain, but the live-attenuated have shown to reduce the risk of anthrax with low adverse events. Here is the latest research on anthrax vaccines.