Computational Study of Bacterial Membrane Disruption by Cationic Biocides: Structural Basis for Water Pore Formation

2014 ◽  
Vol 118 (32) ◽  
pp. 9722-9732 ◽  
Author(s):  
Eric H. Hill ◽  
David G. Whitten ◽  
Deborah G. Evans
Keyword(s):  
Pore Formation ◽  
Computational Study ◽  
Structural Basis ◽  
Membrane Disruption ◽  
Bacterial Membrane ◽  
Water Pore

scholarly journals Correction: Dynamic properties of dipeptidyl peptidase III from Bacteroides thetaiotaomicron and the structural basis for its substrate specificity – a computational study

2017 ◽  
Vol 13 (12) ◽  
pp. 2729-2730
Author(s):  
M. Tomin ◽  
S. Tomić
Keyword(s):  
Substrate Specificity ◽  
Computational Study ◽  
Dynamic Properties ◽  
Dipeptidyl Peptidase ◽  
Structural Basis ◽  
Bacteroides Thetaiotaomicron

Correction for ‘Dynamic properties of dipeptidyl peptidase III from Bacteroides thetaiotaomicron and the structural basis for its substrate specificity – a computational study’ by M. Tomin et al., Mol. BioSyst., 2017, 13, 2407–2417.

Structural Basis for the Mutation-Induced Dysfunction of Human CYP2J2: A Computational Study

2013 ◽  
Vol 53 (6) ◽  
pp. 1350-1357 ◽  
Author(s):  
Shan Cong ◽  
Xiao-Tu Ma ◽  
Yi-Xue Li ◽  
Jing-Fang Wang
Keyword(s):  
Computational Study ◽  
Structural Basis

The structural basis for membrane binding and pore formation by lymphocyte perforin

Nature ◽  
2010 ◽  
Vol 468 (7322) ◽  
pp. 447-451 ◽  
Author(s):  
Ruby H. P. Law ◽  
Natalya Lukoyanova ◽  
Ilia Voskoboinik ◽  
Tom T. Caradoc-Davies ◽  
Katherine Baran ◽  
...  
Keyword(s):  
Pore Formation ◽  
Membrane Binding ◽  
Structural Basis

scholarly journals Alarmone Ap4A is elevated by aminoglycoside antibiotics and enhances their bactericidal activity

2019 ◽  
Vol 116 (19) ◽  
pp. 9578-9585 ◽  
Author(s):  
Xia Ji ◽  
Jin Zou ◽  
Haibo Peng ◽  
Anne-Sophie Stolle ◽  
Ruiqiang Xie ◽  
...  
Keyword(s):  
Therapeutic Index ◽  
Fold Increase ◽  
Multidrug Resistant ◽  
Trna Synthetase ◽  
Aminoglycoside Antibiotics ◽  
Membrane Disruption ◽  
Bacterial Membrane ◽  
Bacterial Killing ◽  
Messenger Molecules ◽  
Increased Susceptibility

Second messenger molecules play important roles in the responses to various stimuli that can determine a cell's fate under stress conditions. Here, we report that lethal concentrations of aminoglycoside antibiotics result in the production of a dinucleotide alarmone metabolite–diadenosine tetraphosphate (Ap4A), which promotes bacterial cell killing by this class of antibiotics. We show that the treatment ofEscherichia coliwith lethal concentrations of kanamycin (Kan) dramatically increases the production of Ap4A. This elevation of Ap4A is dependent on the production of a hydroxyl radical and involves the induction of the Ap4A synthetase lysyl-tRNA synthetase (LysU). Ectopic alteration of intracellular Ap4A concentration via the elimination of the Ap4A phosphatase diadenosine tetraphosphatase (ApaH) and the overexpression of LysU causes over a 5,000-fold increase in bacterial killing by aminoglycosides. This increased susceptibility to aminoglycosides correlates with bacterial membrane disruption. Our findings provide a role for the alarmone Ap4A and suggest that blocking Ap4A degradation or increasing its synthesis might constitute an approach to enhance aminoglycoside killing potency by broadening their therapeutic index and thereby allowing lower nontoxic dosages of these antibiotics to be used in the treatment of multidrug-resistant infections.

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