scholarly journals Discovery of anti-TB agents that target the cell-division protein FtsZ

2010 ◽  
Vol 2 (8) ◽  
pp. 1305-1323 ◽  
Author(s):  
Kunal Kumar ◽  
Divya Awasthi ◽  
William T Berger ◽  
Peter J Tonge ◽  
Richard A Slayden ◽  
...  
Keyword(s):  
Cell Division ◽  
Cell Division Protein

scholarly journals Assembly of bacterial cell division protein FtsZ into dynamic biomolecular condensates

2021 ◽  
Vol 1868 (5) ◽  
pp. 118986 ◽  
Author(s):  
Miguel Ángel Robles-Ramos ◽  
Silvia Zorrilla ◽  
Carlos Alfonso ◽  
William Margolin ◽  
Germán Rivas ◽  
...  
Keyword(s):  
Cell Division ◽  
Bacterial Cell ◽  
Bacterial Cell Division ◽  
Cell Division Protein

scholarly journals Cell division protein DivIB influences the Spo0J/Soj system of chromosome segregation in Bacillus subtilis

2004 ◽  
Vol 55 (2) ◽  
pp. 349-367 ◽  
Author(s):  
Gonçalo Real ◽  
Sabine Autret ◽  
Elizabeth J. Harry ◽  
Jeffery Errington ◽  
Adriano O. Henriques
Keyword(s):  
Bacillus Subtilis ◽  
Cell Division ◽  
Chromosome Segregation ◽  
Cell Division Protein

scholarly journals Patterning of the MinD cell division protein in cells of arbitrary shape can be predicted using a heuristic dispersion relation

2016 ◽  
Vol 3 (1) ◽  
pp. 119-145 ◽  
Author(s):  
James C. Walsh ◽  
◽  
Christopher N. Angstmann ◽  
Anna V. McGann ◽  
Bruce I. Henry ◽  
...  
Keyword(s):  
Cell Division ◽  
Dispersion Relation ◽  
Arbitrary Shape ◽  
Cell Division Protein ◽  
The Mind ◽  
In Cells

scholarly journals Structural reorganization of the bacterial cell-division protein FtsZ fromStaphylococcus aureus

2012 ◽  
Vol 68 (9) ◽  
pp. 1175-1188 ◽  
Author(s):  
Takashi Matsui ◽  
Junji Yamane ◽  
Nobuyuki Mogi ◽  
Hiroto Yamaguchi ◽  
Hiroshi Takemoto ◽  
...  
Keyword(s):  
Cell Division ◽  
Bacterial Cell ◽  
Bacterial Cell Division ◽  
Structural Reorganization ◽  
Cell Division Protein

scholarly journals Cell Division Protein FtsZ Is Unfolded for N-Terminal Degradation by Antibiotic-Activated ClpP

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Nadine Silber ◽  
Stefan Pan ◽  
Sina Schäkermann ◽  
Christian Mayer ◽  
Heike Brötz-Oesterhelt ◽  
...  
Keyword(s):  
Cell Division ◽  
Protein Unfolding ◽  
Multidrug Resistant ◽  
Unexpected Finding ◽  
Bacterial Cells ◽  
Clp Protease ◽  
Content Type ◽  
C Terminus ◽  
Cell Division Protein

ABSTRACT Antibiotic acyldepsipeptides (ADEPs) deregulate ClpP, the proteolytic core of the bacterial Clp protease, thereby inhibiting its native functions and concomitantly activating it for uncontrolled proteolysis of nonnative substrates. Importantly, although ADEP-activated ClpP is assumed to target multiple polypeptide and protein substrates in the bacterial cell, not all proteins seem equally susceptible. In Bacillus subtilis, the cell division protein FtsZ emerged to be particularly sensitive to degradation by ADEP-activated ClpP at low inhibitory ADEP concentrations. In fact, FtsZ is the only bacterial protein that has been confirmed to be degraded in vitro as well as within bacterial cells so far. However, the molecular reason for this preferred degradation remained elusive. Here, we report the unexpected finding that ADEP-activated ClpP alone, in the absence of any Clp-ATPase, leads to an unfolding and subsequent degradation of the N-terminal domain of FtsZ, which can be prevented by the stabilization of the FtsZ fold via nucleotide binding. At elevated antibiotic concentrations, importantly, the C terminus of FtsZ is notably targeted for degradation in addition to the N terminus. Our results show that different target structures are more or less accessible to ClpP, depending on the ADEP level present. Moreover, our data assign a Clp-ATPase-independent protein unfolding capability to the ClpP core of the bacterial Clp protease and suggest that the protein fold of FtsZ may be more flexible than previously anticipated. IMPORTANCE Acyldepsipeptide (ADEP) antibiotics effectively kill multidrug-resistant Gram-positive pathogens, including vancomycin-resistant enterococcus, penicillin-resistant Streptococcus pneumoniae (PRSP), and methicillin-resistant Staphylococcus aureus (MRSA). The antibacterial activity of ADEP depends on a new mechanism of action, i.e., the deregulation of bacterial protease ClpP that leads to bacterial self-digestion. Our data allow new insights into the mode of ADEP action by providing a molecular explanation for the distinct bacterial phenotypes observed at low versus high ADEP concentrations. In addition, we show that ClpP alone, in the absence of any unfoldase or energy-consuming system, and only activated by the small molecule antibiotic ADEP, leads to the unfolding of the cell division protein FtsZ.

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