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@article{Vieira:2022:10.1021/acschembio.2c00276,
author = {Vieira, de Castro G and Worm, D and Grabe, G and Rowan, F and Haggerty, L and Losada, De La Lastra A and Popescu, O and Helaine, S and Barnard, A},
doi = {10.1021/acschembio.2c00276},
journal = {ACS Chemical Biology},
pages = {1598--1606},
title = {Characterisation of the key determinants of Phd antitoxin mediated Doc toxin inactivation in Salmonella},
url = {http://dx.doi.org/10.1021/acschembio.2c00276},
volume = {17},
year = {2022}
}

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TY  - JOUR
AB  - In the search for novel antimicrobial therapeutics, toxin-antitoxin (TA) modules are promising yet underexplored targets for overcoming antibiotic failure. The bacterial toxin Doc has been associated with the persistence of Salmonella in macrophages, enabling its survival upon antibiotic exposure. After developing a novel method to produce the recombinant toxin, we have used antitoxin-mimicking peptides to thoroughly investigate the mechanism by which its cognate antitoxin Phd neutralizes the activity of Doc. We reveal insights into the molecular detail of the Phd–Doc relationship and discriminate antitoxin residues that stabilize the TA complex from those essential for inhibiting the activity of the toxin. Coexpression of Doc and antitoxin peptides in Salmonella was able to counteract the activity of the toxin, confirming our in vitro results with equivalent sequences. Our findings provide key principles for the development of chemical tools to study and therapeutically interrogate this important class of protein–protein interactions.
AU  - Vieira,de Castro G
AU  - Worm,D
AU  - Grabe,G
AU  - Rowan,F
AU  - Haggerty,L
AU  - Losada,De La Lastra A
AU  - Popescu,O
AU  - Helaine,S
AU  - Barnard,A
DO  - 10.1021/acschembio.2c00276
EP  - 1606
PY  - 2022///
SN  - 1554-8929
SP  - 1598
TI  - Characterisation of the key determinants of Phd antitoxin mediated Doc toxin inactivation in Salmonella
T2  - ACS Chemical Biology
UR  - http://dx.doi.org/10.1021/acschembio.2c00276
UR  - http://hdl.handle.net/10044/1/97563
VL  - 17
ER  -

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