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Article ; Online: Microbiology: A beacon for bacterial tubulin.

Harry, Elizabeth J

2014 Volume 516, Issue 7530, Page(s) 175–176

MeSH term(s)	Bacterial Proteins/metabolism ; Cytokinesis ; Cytoskeletal Proteins/metabolism ; Streptococcus pneumoniae/cytology ; Streptococcus pneumoniae/metabolism
Chemical Substances	Bacterial Proteins ; Cytoskeletal Proteins ; FtsZ protein, Bacteria
Language	English
Publishing date	2014-12-11
Publishing country	England
Document type	Comment ; Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature14071
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 9: Show issues
Zs.MO 244: Show issues

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Article ; Online: You Are What You Eat: Metabolic Control of Bacterial Division.

Monahan, Leigh G / Harry, Elizabeth J

Trends in microbiology

2016 Volume 24, Issue 3, Page(s) 181–189

Abstract: Fluctuations in nutrient availability are a fact of life for bacterial cells in the 'wild'. To survive and compete, bacteria must rapidly modulate cell-cycle processes to accommodate changing nutritional conditions and concomitant changes in cell growth. ...

Abstract	Fluctuations in nutrient availability are a fact of life for bacterial cells in the 'wild'. To survive and compete, bacteria must rapidly modulate cell-cycle processes to accommodate changing nutritional conditions and concomitant changes in cell growth. Our understanding of how this is achieved has been transformed in recent years, with cellular metabolism emerging as a central player. Several metabolic enzymes, in addition to their normal catalytic functions, have been shown to directly modulate cell-cycle processes in response to changing nutrient levels. Here we focus on cell division, the final event in the bacterial cell cycle, and discuss recent compelling evidence connecting division regulation to nutritional status and metabolic activity.
MeSH term(s)	Bacillus subtilis/cytology ; Bacillus subtilis/growth & development ; Bacillus subtilis/metabolism ; Bacteria/cytology ; Bacteria/growth & development ; Bacteria/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Cell Cycle/physiology ; Cell Division/genetics ; Cytoskeletal Proteins/metabolism ; Escherichia coli/cytology ; Escherichia coli/growth & development ; Escherichia coli/metabolism ; Gene Expression Regulation, Bacterial
Chemical Substances	Bacterial Proteins ; Cytoskeletal Proteins ; FtsZ protein, Bacteria
Language	English
Publishing date	2016-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/j.tim.2015.11.007
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Zs.A 3738: Show issues

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Article ; Online: A newly identified prophage-encoded gene,

Ansari, Shirin / Walsh, James C / Bottomley, Amy L / Duggin, Iain G / Burke, Catherine / Harry, Elizabeth J

Journal of bacteriology

2021 Volume 203, Issue 11

Abstract: Rod-shaped bacteria such ... ...

Abstract	Rod-shaped bacteria such as
Language	English
Publishing date	2021-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.00646-20
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Ud II Zs.50: Show issues

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Article ; Online: Synthesis and biological evaluation of 3,5-substituted pyrazoles as possible antibacterial agents.

Payne, Matthew / Bottomley, Amy L / Och, Anthony / Asmara, Anjar P / Harry, Elizabeth J / Ung, Alison T

Bioorganic & medicinal chemistry

2021 Volume 48, Page(s) 116401

Abstract: The emergence of multi-drug resistant bacteria has increased the need for novel antibiotics to help overcome what may be considered the greatest threat to modern medicine. Here we report the synthesis of fifteen novel 3,5-diaryl-1H- pyrazoles obtained ... ...

Abstract	The emergence of multi-drug resistant bacteria has increased the need for novel antibiotics to help overcome what may be considered the greatest threat to modern medicine. Here we report the synthesis of fifteen novel 3,5-diaryl-1H- pyrazoles obtained via one-pot cyclic oxidation of a chalcone and hydrazine-monohydrate. The synthesised pyrazoles were then screened against Staphylococcus aureus and Escherichia coli to determine their antibacterial potential. The results show that compound 7p is bacteriostatic at MIC 8 µg/mL. The compound is non-toxic against healthy mammalian cells, 3T3-L1 at the highest test concentration 50 µg/mL. Furthermore, compound 7p significantly affected bacterial morphogenesis before cell lysis in Bacillus subtilis when treated above the MIC concentration. From the results, a promising lead compound was identified for future development.
MeSH term(s)	Anti-Bacterial Agents/chemical synthesis ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Bacillus subtilis/drug effects ; Dose-Response Relationship, Drug ; Escherichia coli/drug effects ; Microbial Sensitivity Tests ; Molecular Structure ; Pyrazoles/chemical synthesis ; Pyrazoles/chemistry ; Pyrazoles/pharmacology ; Staphylococcus aureus/drug effects ; Structure-Activity Relationship
Chemical Substances	Anti-Bacterial Agents ; Pyrazoles
Language	English
Publishing date	2021-09-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1161284-8
ISSN	1464-3391 ; 0968-0896
ISSN (online)	1464-3391
ISSN	0968-0896
DOI	10.1016/j.bmc.2021.116401
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Zs.A 3815: Show issues

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Article ; Online: Synthesis and biological evaluation of tetrahydroisoquinoline-derived antibacterial compounds.

Payne, Matthew / Bottomley, Amy L / Och, Anthony / Hiscocks, Hugh G / Asmara, Anjar P / Harry, Elizabeth J / Ung, Alison T

Bioorganic & medicinal chemistry

2022 Volume 57, Page(s) 116648

Abstract: Antibiotic resistance is one of the greatest threats to modern medicine. Drugs that were once routinely used to treat infections are being rendered ineffective, increasing the demand for novel antibiotics with low potential for resistance. Here we report ...

Abstract	Antibiotic resistance is one of the greatest threats to modern medicine. Drugs that were once routinely used to treat infections are being rendered ineffective, increasing the demand for novel antibiotics with low potential for resistance. Here we report the synthesis of 18 novel cationic tetrahydroisoquinoline-triazole compounds. Five of the developed molecules were active against S. aureus at a low MIC of 2-4 μg/mL. Hit compound 4b was also found to eliminate M. tuberculosis H37Rv at MIC of 6 μg/mL. This potent molecule was found to eliminate S. aureus effectively, with no resistance observed after thirty days of sequential passaging. These results identified compound 4b and its analogues as potential candidates for further drug development that could help tackle the threat of antibiotic resistance.
MeSH term(s)	Anti-Bacterial Agents/chemical synthesis ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Dose-Response Relationship, Drug ; Microbial Sensitivity Tests ; Molecular Structure ; Mycobacterium tuberculosis/drug effects ; Staphylococcus aureus/drug effects ; Structure-Activity Relationship ; Tetrahydroisoquinolines/chemical synthesis ; Tetrahydroisoquinolines/chemistry ; Tetrahydroisoquinolines/pharmacology
Chemical Substances	Anti-Bacterial Agents ; Tetrahydroisoquinolines
Language	English
Publishing date	2022-02-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1161284-8
ISSN	1464-3391 ; 0968-0896
ISSN (online)	1464-3391
ISSN	0968-0896
DOI	10.1016/j.bmc.2022.116648
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Zs.A 3815: Show issues

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Article ; Online: The ParB homologs, Spo0J and Noc, together prevent premature midcell Z ring assembly when the early stages of replication are blocked in Bacillus subtilis.

Hajduk, Isabella V / Mann, Riti / Rodrigues, Christopher D A / Harry, Elizabeth J

Molecular microbiology

2019 Volume 112, Issue 3, Page(s) 766–784

Abstract: Precise cell division in coordination with DNA replication and segregation is of utmost importance for all organisms. The earliest stage of cell division is the assembly of a division protein FtsZ into a ring, known as the Z ring, at midcell. What still ... ...

Abstract	Precise cell division in coordination with DNA replication and segregation is of utmost importance for all organisms. The earliest stage of cell division is the assembly of a division protein FtsZ into a ring, known as the Z ring, at midcell. What still eludes us, however, is how bacteria precisely position the Z ring at midcell. Work in B. subtilis over the last two decades has identified a link between the early stages of DNA replication and cell division. A recent model proposed that the progression of the early stages of DNA replication leads to an increased ability for the Z ring to form at midcell. This model arose through studies examining Z ring position in mutants blocked at different steps of the early stages of DNA replication. Here, we show that this model is unlikely to be correct and the mutants previously studied generate nucleoids with different capacity for blocking midcell Z ring assembly. Importantly, our data suggest that two proteins of the widespread ParB family, Noc and Spo0J are required to prevent Z ring assembly over the bacterial nucleoid and help fine tune the assembly of the Z ring at midcell during the cell cycle.
MeSH term(s)	Bacillus subtilis/cytology ; Bacillus subtilis/genetics ; Bacillus subtilis/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Cell Cycle ; Cell Division ; DNA Replication ; Gene Expression Regulation, Bacterial
Chemical Substances	Bacterial Proteins ; spore-specific proteins, Bacillus
Language	English
Publishing date	2019-06-11
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/mmi.14319
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Zs.A 2502: Show issues

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Article ; Online: Uncovering novel susceptibility targets to enhance the efficacy of third-generation cephalosporins against ESBL-producing uropathogenic Escherichia coli.

Phan, Minh-Duy / Bottomley, Amy L / Peters, Kate M / Harry, Elizabeth J / Schembri, Mark A

The Journal of antimicrobial chemotherapy

2020 Volume 75, Issue 6, Page(s) 1415–1423

Abstract: Background: Uropathogenic Escherichia coli (UPEC) are a major cause of urinary tract infection (UTI), one of the most common infectious diseases in humans. UPEC are increasingly associated with resistance to multiple antibiotics. This includes ... ...

Abstract	Background: Uropathogenic Escherichia coli (UPEC) are a major cause of urinary tract infection (UTI), one of the most common infectious diseases in humans. UPEC are increasingly associated with resistance to multiple antibiotics. This includes resistance to third-generation cephalosporins, a common class of antibiotics frequently used to treat UTI. Methods: We employed a high-throughput genome-wide screen using saturated transposon mutagenesis and transposon directed insertion-site sequencing (TraDIS) together with phenotypic resistance assessment to identify key genes required for survival of the MDR UPEC ST131 strain EC958 in the presence of the third-generation cephalosporin cefotaxime. Results: We showed that blaCMY-23 is the major ESBL gene in EC958 responsible for mediating resistance to cefotaxime. Our screen also revealed that mutation of genes involved in cell division and the twin-arginine translocation pathway sensitized EC958 to cefotaxime. The role of these cell-division and protein-secretion genes in cefotaxime resistance was confirmed through the construction of mutants and phenotypic testing. Mutation of these genes also sensitized EC958 to other cephalosporins. Conclusions: This work provides an exemplar for the application of TraDIS to define molecular mechanisms of resistance to antibiotics. The identification of mutants that sensitize UPEC to cefotaxime, despite the presence of a cephalosporinase, provides a framework for the development of new approaches to treat infections caused by MDR pathogens.
MeSH term(s)	Cephalosporins/pharmacology ; Escherichia coli Infections/drug therapy ; Escherichia coli Proteins/genetics ; Humans ; Mutagenesis ; Urinary Tract Infections/drug therapy ; Uropathogenic Escherichia coli/genetics
Chemical Substances	Cephalosporins ; Escherichia coli Proteins
Language	English
Publishing date	2020-02-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkaa023
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Zs.A 1197: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 124: Show issues

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Article ; Online: Connecting the dots of the bacterial cell cycle: Coordinating chromosome replication and segregation with cell division.

Hajduk, Isabella V / Rodrigues, Christopher D A / Harry, Elizabeth J

Seminars in cell & developmental biology

2016 Volume 53, Page(s) 2–9

Abstract: Proper division site selection is crucial for the survival of all organisms. What still eludes us is how bacteria position their division site with high precision, and in tight coordination with chromosome replication and segregation. Until recently, the ...

Abstract	Proper division site selection is crucial for the survival of all organisms. What still eludes us is how bacteria position their division site with high precision, and in tight coordination with chromosome replication and segregation. Until recently, the general belief, at least in the model organisms Bacillus subtilis and Escherichia coli, was that spatial regulation of division comes about by the combined negative regulatory mechanisms of the Min system and nucleoid occlusion. However, as we review here, these two systems cannot be solely responsible for division site selection and we highlight additional regulatory mechanisms that are at play. In this review, we put forward evidence of how chromosome replication and segregation may have direct links with cell division in these bacteria and the benefit of recent advances in chromosome conformation capture techniques in providing important information about how these three processes mechanistically work together to achieve accurate generation of progenitor cells.
Language	English
Publishing date	2016-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2015.11.012
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Zs.A 2918: Show issues

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Article ; Online: FtsZ as an Antibacterial Target: Status and Guidelines for Progressing This Avenue.

Kusuma, Kennardy D / Payne, Matthew / Ung, Alison T / Bottomley, Amy L / Harry, Elizabeth J

ACS infectious diseases

2019 Volume 5, Issue 8, Page(s) 1279–1294

Abstract: The disturbing increase in the number of bacterial pathogens that are resistant to multiple, or sometimes all, current antibiotics highlights the desperate need to pursue the discovery and development of novel classes of antibacterials. The wealth of ... ...

Abstract	The disturbing increase in the number of bacterial pathogens that are resistant to multiple, or sometimes all, current antibiotics highlights the desperate need to pursue the discovery and development of novel classes of antibacterials. The wealth of knowledge available about the bacterial cell division machinery has aided target-driven approaches to identify new inhibitor compounds. The main division target being pursued is the highly conserved and essential protein FtsZ. Despite very active research on FtsZ inhibitors for several years, this protein is not yet targeted by any commercial antibiotic. Here, we discuss the suitability of FtsZ as an antibacterial target for drug development and review progress achieved in this area. We use hindsight to highlight the gaps that have slowed progress in FtsZ inhibitor development and to suggest guidelines for concluding that FtsZ is actually the target of these molecules, a key missing link in several studies. In moving forward, a multidisciplinary, communicative, and collaborative process, with sharing of research expertise, is critical if we are to succeed.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Bacteria/chemistry ; Bacteria/drug effects ; Bacterial Proteins/antagonists & inhibitors ; Bacterial Proteins/chemistry ; Cell Division ; Clinical Trials as Topic ; Cytoskeletal Proteins/antagonists & inhibitors ; Cytoskeletal Proteins/chemistry ; Drug Discovery ; Humans ; Research
Chemical Substances	Anti-Bacterial Agents ; Bacterial Proteins ; Cytoskeletal Proteins ; FtsZ protein, Bacteria
Language	English
Publishing date	2019-07-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2373-8227
ISSN (online)	2373-8227
DOI	10.1021/acsinfecdis.9b00055
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Article ; Online: Immobilization Techniques of Bacteria for Live Super-resolution Imaging Using Structured Illumination Microscopy.

Bottomley, Amy L / Turnbull, Lynne / Whitchurch, Cynthia B / Harry, Elizabeth J

Methods in molecular biology (Clifton, N.J.)

2017 Volume 1535, Page(s) 197–209

Abstract: Advancements in optical microscopy technology have allowed huge progression in the ability to understand protein structure and dynamics in live bacterial cells using fluorescence microscopy. Paramount to high-quality microscopy is good sample preparation ...

Abstract	Advancements in optical microscopy technology have allowed huge progression in the ability to understand protein structure and dynamics in live bacterial cells using fluorescence microscopy. Paramount to high-quality microscopy is good sample preparation to avoid bacterial cell movement that can result in motion blur during image acquisition. Here, we describe two techniques of sample preparation that reduce unwanted cell movement and are suitable for application to a number of bacterial species and imaging methods.
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-6673-8_12
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