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  1. Article: Repurposing drugs with specific activity against L-form bacteria.

    Emami, Kaveh / Banks, Peter / Wu, Ling Juan / Errington, Jeffery

    Frontiers in microbiology

    2023  Volume 14, Page(s) 1097413

    Abstract: Cell wall deficient "L- form" bacteria are of growing medical interest as a possible source of recurrent or persistent infection, largely because of their complete resistance to cell wall active antibiotics such as β-lactams. Antibiotics that ... ...

    Abstract Cell wall deficient "L- form" bacteria are of growing medical interest as a possible source of recurrent or persistent infection, largely because of their complete resistance to cell wall active antibiotics such as β-lactams. Antibiotics that specifically kill L-forms would be of potential interest as therapeutics, but also as reagents with which to explore the role of L-forms in models of recurrent infection. To look for specific anti-L-form antibiotics, we screened a library of several hundred FDA-approved drugs and identified compounds highly selective for L-form killing. Among the compounds identified were representatives of two different classes of calcium channel blockers: dihydropyridines, e.g., manidipine; and diphenylmethylpiperazine, e.g., flunarizine. Mode of action studies suggested that both classes of compound work by decreasing membrane fluidity. This leads to a previously recognized phenotype of L-forms in which the cells can continue to enlarge but fail to divide. We identified a considerable degree of variation in the activity of different representatives of the two classes of compounds, suggesting that it may be possible to modify them for use as drugs for L-form-dependent infections.
    Language English
    Publishing date 2023-04-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2023.1097413
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Microbe Profile:

    Errington, Jeffery / Aart, Lizah T van der

    Microbiology (Reading, England)

    2020  Volume 166, Issue 5, Page(s) 425–427

    Abstract: ... Bacillus ... ...

    Abstract Bacillus subtilis
    MeSH term(s) Bacillus subtilis/physiology ; Biofilms ; Genome, Bacterial ; Industrial Microbiology ; Phylogeny ; Spores/physiology
    Language English
    Publishing date 2020-05-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1180712-x
    ISSN 1465-2080 ; 1350-0872
    ISSN (online) 1465-2080
    ISSN 1350-0872
    DOI 10.1099/mic.0.000922
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Dynamic proteins and a cytoskeleton in bacteria.

    Errington, Jeffery

    Nature cell biology

    2003  Volume 5, Issue 3, Page(s) 175–178

    MeSH term(s) Bacteria/genetics ; Bacteria/metabolism ; Bacterial Proteins/metabolism ; Cell Cycle Proteins/metabolism ; Cytoskeleton/metabolism ; DNA Replication ; Microscopy, Fluorescence ; Protein Biosynthesis ; Transcription, Genetic
    Chemical Substances Bacterial Proteins ; Cell Cycle Proteins
    Language English
    Publishing date 2003-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/ncb0303-175
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Correction: Screening and purification of natural products from actinomycetes that affect the cell shape of fission yeast (doi:10.1242/jcs.194571).

    Lewis, Richard A / Li, Juanjuan / Allenby, Nicholas E E / Errington, Jeffery / Hayle, Jacqueline / Nurse, Paul

    Journal of cell science

    2018  Volume 131, Issue 13

    Language English
    Publishing date 2018-07-04
    Publishing country England
    Document type Journal Article ; Published Erratum
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.221580
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Screening and purification of natural products from actinomycetes that affect the cell shape of fission yeast.

    Lewis, Richard A / Li, Juanjuan / Allenby, Nicholas E E / Errington, Jeffery / Hayles, Jacqueline / Nurse, Paul

    Journal of cell science

    2017  Volume 130, Issue 18, Page(s) 3173–3185

    Abstract: This study was designed to identify bioactive compounds that alter the cellular shape of the fission ... ...

    Abstract This study was designed to identify bioactive compounds that alter the cellular shape of the fission yeast
    MeSH term(s) Actinomyces/chemistry ; Biological Products/analysis ; Biological Products/isolation & purification ; Biological Products/pharmacology ; Cell Shape/drug effects ; Checkpoint Kinase 1/metabolism ; Cycloheximide/pharmacology ; DNA Damage ; Drug Evaluation, Preclinical ; Fatty Acids, Unsaturated/pharmacology ; Phenotype ; Schizosaccharomyces/cytology ; Schizosaccharomyces/drug effects ; Spectrometry, Mass, Electrospray Ionization
    Chemical Substances Biological Products ; Fatty Acids, Unsaturated ; Cycloheximide (98600C0908) ; Checkpoint Kinase 1 (EC 2.7.11.1) ; leptomycin B (Y031I2N1EO)
    Language English
    Publishing date 2017-08-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.194571
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: ftsZ mutations affecting cell division frequency, placement and morphology in Bacillus subtilis.

    Feucht, Andrea / Errington, Jeffery

    Microbiology (Reading, England)

    2005  Volume 151, Issue Pt 6, Page(s) 2053–2064

    Abstract: A key event in cytokinesis in bacteria is the assembly of the essential division protein FtsZ into ring-like structures at the nascent division site. FtsZ is the prokaryotic homologue of tubulin, and is found in nearly all bacteria. In vitro, FtsZ ... ...

    Abstract A key event in cytokinesis in bacteria is the assembly of the essential division protein FtsZ into ring-like structures at the nascent division site. FtsZ is the prokaryotic homologue of tubulin, and is found in nearly all bacteria. In vitro, FtsZ polymerizes in the presence of GTP to form higher-ordered polymers. FtsZ consists of two domains, with the GTP-binding site located in the N-terminal domain. The less-conserved C-terminal domain contains residues important for GTP hydrolysis, but its overall function is still unclear. This paper reports the development of a simple strategy to generate mutations in the essential division gene ftsZ. Nine novel and viable ftsZ mutants of Bacillus subtilis are described. Eight of the mutations would affect the C-terminus of FtsZ. The collection of mutants exhibits a range of morphological phenotypes, ranging from normal to highly filamentous cells; some produce minicells, or divide in a twisted configuration; one mutation has a temperature-sensitive effect specifically impairing sporulation. The sites of the amino acid changes generated by the mutations could be informative about FtsZ function and its protein-protein interactions.
    MeSH term(s) Amino Acid Substitution ; Bacillus subtilis/cytology ; Bacillus subtilis/genetics ; Bacillus subtilis/growth & development ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/physiology ; Cell Division/genetics ; Cytoskeletal Proteins/chemistry ; Cytoskeletal Proteins/genetics ; Cytoskeletal Proteins/physiology ; Models, Molecular ; Morphogenesis/genetics ; Mutagenesis ; Mutation ; Protein Structure, Tertiary ; Recombination, Genetic ; Spores, Bacterial/genetics ; Spores, Bacterial/physiology
    Chemical Substances Bacterial Proteins ; Cytoskeletal Proteins ; FtsZ protein, Bacteria
    Language English
    Publishing date 2005-06-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180712-x
    ISSN 1465-2080 ; 1350-0872
    ISSN (online) 1465-2080
    ISSN 1350-0872
    DOI 10.1099/mic.0.27899-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: PBP1 is a component of the Bacillus subtilis cell division machinery.

    Scheffers, Dirk-Jan / Errington, Jeffery

    Journal of bacteriology

    2004  Volume 186, Issue 15, Page(s) 5153–5156

    Abstract: Bacillus subtilis penicillin-binding protein PBP1 has been implicated in cell division. We show here that a PBP1 knockout strain is affected in the formation of the asymmetric sporulation septum and that green fluorescent protein-PBP1 localizes to the ... ...

    Abstract Bacillus subtilis penicillin-binding protein PBP1 has been implicated in cell division. We show here that a PBP1 knockout strain is affected in the formation of the asymmetric sporulation septum and that green fluorescent protein-PBP1 localizes to the sporulation septum. Localization of PBP1 to the vegetative septum is dependent on various cell division proteins. This study proves that PBP1 forms part of the B. subtilis cell division machinery.
    MeSH term(s) Bacillus subtilis/genetics ; Bacillus subtilis/metabolism ; Bacillus subtilis/physiology ; Bacterial Proteins ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Division/physiology ; Gene Expression Regulation, Bacterial ; Green Fluorescent Proteins ; Luminescent Proteins/genetics ; Luminescent Proteins/metabolism ; Penicillin-Binding Proteins ; Recombinant Fusion Proteins/metabolism ; Spores, Bacterial/physiology
    Chemical Substances Bacterial Proteins ; Carrier Proteins ; Cell Cycle Proteins ; Luminescent Proteins ; Penicillin-Binding Proteins ; Recombinant Fusion Proteins ; Green Fluorescent Proteins (147336-22-9)
    Language English
    Publishing date 2004-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2968-3
    ISSN 1098-5530 ; 0021-9193
    ISSN (online) 1098-5530
    ISSN 0021-9193
    DOI 10.1128/JB.186.15.5153-5156.2004
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  8. Article ; Online: Regulation of cell wall morphogenesis in Bacillus subtilis by recruitment of PBP1 to the MreB helix.

    Kawai, Yoshikazu / Daniel, Richard A / Errington, Jeffery

    Molecular microbiology

    2009  Volume 71, Issue 5, Page(s) 1131–1144

    Abstract: The bacterial actin homologue MreB plays a key role in cell morphogenesis. In Bacillus subtilis MreB is essential under normal growth conditions and mreB mutants are defective in the control of cell diameter. However, the precise role of MreB is still ... ...

    Abstract The bacterial actin homologue MreB plays a key role in cell morphogenesis. In Bacillus subtilis MreB is essential under normal growth conditions and mreB mutants are defective in the control of cell diameter. However, the precise role of MreB is still unclear. Analysis of the lethal phenotypic consequences of mreB disruption revealed an unusual bulging phenotype that precedes cell death. A similar phenotype was seen in wild-type cells at very low Mg(2+) concentrations. We found that inactivation of the major bi-functional penicillin-binding protein (PBP) PBP1 of B. subtilis restored the viability of an mreB null mutant as well as preventing bulging in both mutant and wild-type backgrounds. Bulging was associated with delocalization of PBP1. We show that the normal pattern of localization of PBP1 is dependent on MreB and that the proteins can physically interact using in vivo pull-down and bacterial two-hybrid approaches. Interactions between MreB and several other PBPs were also detected. Our results suggest that MreB filaments associate directly with the peptidoglycan biosynthetic machinery in B. subtilis as part of the mechanism that brings about controlled cell elongation.
    MeSH term(s) Bacillus subtilis/cytology ; Bacillus subtilis/genetics ; Bacillus subtilis/metabolism ; Cell Wall/physiology ; Mutagenesis ; Mutation ; Penicillin-Binding Proteins/genetics ; Penicillin-Binding Proteins/metabolism ; Peptidoglycan/metabolism
    Chemical Substances Penicillin-Binding Proteins ; Peptidoglycan
    Language English
    Publishing date 2009-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/j.1365-2958.2009.06601.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Partial functional redundancy of MreB isoforms, MreB, Mbl and MreBH, in cell morphogenesis of Bacillus subtilis.

    Kawai, Yoshikazu / Asai, Kei / Errington, Jeffery

    Molecular microbiology

    2009  Volume 73, Issue 4, Page(s) 719–731

    Abstract: MreB proteins are bacterial actin homologues thought to have a role in cell shape determination by positioning the cell wall synthetic machinery. Many bacteria, particularly Gram-positives, have more than one MreB isoform. Bacillus subtilis has three, ... ...

    Abstract MreB proteins are bacterial actin homologues thought to have a role in cell shape determination by positioning the cell wall synthetic machinery. Many bacteria, particularly Gram-positives, have more than one MreB isoform. Bacillus subtilis has three, MreB, Mbl and MreBH, which colocalize in a single helical structure. We now show that the helical pattern of peptidoglycan (PG) synthesis in the cylindrical part of the rod-shaped cell is governed by the redundant action of the three MreB isoforms. Single mutants for any one of mreB isoforms can still incorporate PG in a helical pattern and generate a rod shape. However, after depletion of MreB in an mbl mutant (or depletion of all three isoforms) lateral wall PG synthesis was impaired and the cells became spherical and lytic. Overexpression of any one of the MreB isoforms overcame the lethality as well as the defects in lateral PG synthesis and cell shape. Furthermore, MreB and Mbl can associate with the peptidoglycan biosynthetic machinery independently. However, no single MreB isoform was able to support normal growth under various stress conditions, suggesting that the multiple isoforms are used to allow cells to maintain proper growth and morphogenesis under changing and sometimes adverse conditions.
    MeSH term(s) Bacillus subtilis/cytology ; Bacillus subtilis/genetics ; Bacillus subtilis/growth & development ; Bacillus subtilis/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Cell Wall/metabolism ; Cytoskeletal Proteins/genetics ; Cytoskeletal Proteins/metabolism ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Microbial Viability ; Morphogenesis ; Mutation ; Peptidoglycan/biosynthesis ; Protein Isoforms/genetics ; Protein Isoforms/metabolism
    Chemical Substances Bacterial Proteins ; Cytoskeletal Proteins ; Peptidoglycan ; Protein Isoforms ; mbl protein, Bacillus subtilis
    Language English
    Publishing date 2009-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/j.1365-2958.2009.06805.x
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  10. Article: A magnesium-dependent mreB null mutant: implications for the role of mreB in Bacillus subtilis.

    Formstone, Alex / Errington, Jeffery

    Molecular microbiology

    2004  Volume 55, Issue 6, Page(s) 1646–1657

    Abstract: MreB shares a common prokaryotic ancestor with actin and is present in almost all rod-shaped bacteria. MreB proteins have been implicated in a range of important cell processes, including cell morphogenesis, chromosome segregation and cell polarity. The ... ...

    Abstract MreB shares a common prokaryotic ancestor with actin and is present in almost all rod-shaped bacteria. MreB proteins have been implicated in a range of important cell processes, including cell morphogenesis, chromosome segregation and cell polarity. The mreB gene frequently lies at the beginning of a cluster of genes, immediately upstream of the conserved mreC and mreD genes. RNA analysis showed that in Bacillus subtilis mreB is co-transcribed with mreC and that these genes form part of an operon under the control of a promoter(s) upstream of mreB. Construction of an in-frame deletion of mreB and its complementation by mreB(+) only, in trans, established that the gene is important for maintenance of cell width and cell viability under normal growth conditions, independent of polar effects on downstream genes. Remarkably, virtually normal growth was restored to the mreB null mutant in the presence of high concentrations of magnesium, especially when high concentrations of the osmoprotectant, sucrose were also present. Under these conditions, cells could be maintained in the complete absence of an mreB gene, with almost normal morphology. No detectable effect on chromosome segregation was evident in the mutant, nor was there an effect on the topology of nascent peptidoglycan insertion. A GFP-MreB fusion was used to look at the localization of MreB in live cells. The pattern of localization was similar to that previously described, but no tight linkage to nucleoid positioning was evident. Propagation of the mreB null mutant in the absence of magnesium and sucrose led to a progressive increase in cell width, culminating in cell lysis. Cell division was also perturbed but this effect may be secondary to the disturbance in cell width. These results suggest that the major role of MreB in B. subtilis lies in the control of cell diameter.
    MeSH term(s) Bacillus subtilis/chemistry ; Bacillus subtilis/genetics ; Bacillus subtilis/growth & development ; Bacillus subtilis/physiology ; Bacterial Proteins/genetics ; Bacterial Proteins/physiology ; Cell Wall/metabolism ; Chromosome Segregation ; Chromosomes, Bacterial/metabolism ; Gene Deletion ; Genes, Bacterial ; Genes, Essential ; Genes, Reporter ; Genetic Complementation Test ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Magnesium/metabolism ; Morphogenesis/genetics ; Mutation ; Osmotic Pressure ; Peptidoglycan/metabolism ; Recombinant Fusion Proteins/analysis ; Recombinant Fusion Proteins/genetics ; Sequence Deletion ; Sucrose
    Chemical Substances Bacterial Proteins ; Peptidoglycan ; Recombinant Fusion Proteins ; Green Fluorescent Proteins (147336-22-9) ; Sucrose (57-50-1) ; Magnesium (I38ZP9992A)
    Language English
    Publishing date 2004-11-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/j.1365-2958.2005.04506.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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