Toggle Main Menu Toggle Search

ePrints

Multiple effects of benzamide antibiotics on FtsZ function

Lookup NU author(s): Dr David Adams, Dr Ling Juan Wu, Professor Jeff Errington

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

P>Cell division in almost all bacteria is orchestrated by the essential tubulin homologue FtsZ, which assembles into a ring-like structure and acts as a scaffold for the division machinery. Division was recently validated as an important target for antibiotics by the demonstration that low-molecular-weight inhibitors of FtsZ, called benzamides, can cure mice infected with Staphylococcus aureus. In treated cells of Bacillus subtilis we show that FtsZ assembles into foci throughout the cell, including abnormal locations at the cell poles and over the nucleoid. These foci are not inactive aggregates because they remain dynamic, turning over almost as rapidly as untreated polymers. Remarkably, although division is completely blocked, the foci efficiently recruit division proteins that normally co-assemble with FtsZ. However, they show no affinity for components of the Min or Nucleoid occlusion systems. In vitro, the benzamides strongly promote the polymerization of FtsZ, into hyperstable polymers, which are highly curved. Importantly, even at low concentrations, benzamides transform the structure of the Z ring, resulting in abnormal helical cell division events. We propose that benzamides act principally by promoting an FtsZ protomer conformation that is incompatible with a higher-order level of assembly needed to make a division ring.


Publication metadata

Author(s): Adams DW, Wu LJ, Czaplewski LG, Errington J

Publication type: Article

Publication status: Published

Journal: Molecular Microbiology

Year: 2011

Volume: 80

Issue: 1

Pages: 68-84

Print publication date: 15/02/2011

ISSN (print): 0950-382X

ISSN (electronic): 1365-2958

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/j.1365-2958.2011.07559.x

DOI: 10.1111/j.1365-2958.2011.07559.x


Altmetrics

Altmetrics provided by Altmetric


Actions

    Link to this publication


Share