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Sporulation in mycobacteria
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
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2009 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 26, 10781-10786 p.Article in journal (Refereed) Published
Abstract [en]

Mycobacteria owe their success as pathogens to their ability to persist for long periods within host cells in asymptomatic, latent forms before they opportunistically switch to the virulent state. The molecular mechanisms underlying the transition into dormancy and emergence from it are not clear. Here we show that old cultures of Mycobacterium marinum contained spores that, upon exposure to fresh medium, germinated into vegetative cells and reappeared again in stationary phase via endospore formation. They showed many of the usual characteristics of well-known endospores. Homologues of well-known sporulation genes of Bacillus subtilis and Streptomyces coelicolor were detected in mycobacteria genomes, some of which were verified to be transcribed during appropriate life-cycle stages. We also provide data indicating that it is likely that old Mycobacterium bovis bacillus Calmette-Guérin cultures form spores. Together, our data show sporulation as a lifestyle adapted by mycobacteria under stress and tempt us to suggest this as a possible mechanism for dormancy and/or persistent infection. If so, this might lead to new prophylactic strategies.

Place, publisher, year, edition, pages
2009. Vol. 106, no 26, 10781-10786 p.
Keyword [en]
Mycobacterium marinum, cell division, DNA replication, cell cycle, endosporulation
National Category
Biological Sciences
Research subject
Microbiology
Identifiers
URN: urn:nbn:se:uu:diva-106192DOI: 10.1073/pnas.0904104106ISI: 000267564300071PubMedID: 19541637OAI: oai:DiVA.org:uu-106192DiVA: diva2:224222
Available from: 2009-06-17 Created: 2009-06-17 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Dynamic Organization of Molecular Machines in Bacteria
Open this publication in new window or tab >>Dynamic Organization of Molecular Machines in Bacteria
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bacterial cells were once treated as membrane-enclosed bags of cytoplasm: a homogeneous, undifferentiated suspension in which polymers (proteins, nucleic acids, etc.) and small molecules diffused freely to interact with each other. Biochemical studies have determined the molecular mechanisms underlying the biological processes of metabolism, replication and transcription-translation, etc. However, recent advancements in optical techniques armed with fluorescent tags for proteins and nucleic acids have increased our ability to peer into the interior of live bacterial cells. This has revealed an organized layout of multi-protein complexes, or molecular machines, dedicated to specific functions at defined sub-cellular locations; the timing of their assembly and/or rates of their activity being determined by available nutrition and environmental signals from the niche occupied by the organism.

In the present study, we have attempted to identify the intracellular location and organization of the molecular machines assembled for protein synthesis (ribosomes), DNA replication (replisomes) and cell division (divisome) in different bacteria. We have used the model system Escherichia coli as well as Helicobacter pylori and mycobacterial strains (Mycobacterium marinum and Mycobacterium smegmatis), which grow at different rates and move to dormancy late into stationary phase

Bacterial nucleoid plays a major role in organizing the location and movement of active ribosomes, replisomes and placement of divisome. While the active ribosomes appear to follow the dynamic folds of the bacterial nucleoid during cell growth in E. coli, inactive ribosomes appear to accumulate near the periphery. The replisome in H. pylori was visualized as a sharp, single focus upon SSB and DnaB co-localization in growing helical rods but disassembled into diffused fluorescence when the cells attained non-replicative coccoid stage. Our investigation into mycobacterial life-cycle revealed unique features such as an absence of a dedicated mid-cell site for divisome assembly and endosporulation upon entry into stationary phase.

In brief, we present the cell cycle-dependent subcellular organization of molecular machines in bacteria. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 48 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 847
Keyword
molecular machines, bacteria, cell cycle, ribosome, replisome, divisome, spore, E. coli, H. pylori, Mycobacteria
National Category
Microbiology
Research subject
Microbiology
Identifiers
urn:nbn:se:uu:diva-157691 (URN)978-91-554-8140-7 (ISBN)
Public defence
2011-10-14, Room B41, Biomedicinskt centrum (BMC), Husargatan 3, Uppsala, 13:15 (English)
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Supervisors
Available from: 2011-09-23 Created: 2011-08-22 Last updated: 2013-03-14Bibliographically approved

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