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Biomedical subjects

Ronen Hazan

Publications and source records attributed to Ronen Hazan.

7 recordsLinked to original sources
PubMed2006

Resolving chromosome segregation in bacteria.

Bacterial chromosomes are evenly distributed between daughter cells, however no equivalent eukaryotic mitotic apparatus has been identified yet. Nevertheless, an advance in our understanding of the dynamics of the bacterial chromosome has been accomplished in recent years by adopting fluorescence microscopy techniques to visualize living bacterial cells. Here, some of the most recent studies that yield new insights into the nature of bacterial chromosome dynamics are described. In addition, we review in detail the current models that attempt to illuminate the mechanism of chromosome segregation in bacteria and discuss the possibility that a bacterial mitotic apparatus does indeed exist.

Actins↗
PubMed2006

Bacterial programmed cell death and multicellular behavior in bacteria.

Traditionally, programmed cell death (PCD) is associated with eukaryotic multicellular organisms. However, recently, PCD systems have also been observed in bacteria. Here we review recent research on two kinds of genetic programs that promote bacterial cell death. The first is mediated by mazEF, a toxin-antitoxin module found in the chromosomes of many kinds of bacteria, and mainly studied in Escherichia coli. The second program is found in Bacillus subtilis, in which the skf and sdp operons mediate the death of a subpopulation of sporulating bacterial cells. We relate these two bacterial PCD systems to the ways in which bacterial populations resemble multicellular organisms.

Antitoxins↗
PubMed2005

mazEF: a chromosomal toxin-antitoxin module that triggers programmed cell death in bacteria.

mazEF is a toxin-antitoxin module located on the Escherichia coli chromosome and that of some other bacteria, including pathogens. mazF specifies for a stable toxin, MazF, and mazE specifies for a labile antitoxin, MazE, that antagonizes MazF. MazF is a sequence-specific mRNA endoribonuclease that initiates a programmed cell death pathway in response to various stresses. The mazEF-mediated death pathway can act as a defense mechanism that prevents the spread of bacterial phage infection, allowing bacterial populations to behave like multicellular organisms.

Apoptosis↗
PubMed2004

Bacterial programmed cell death systems as targets for antibiotics.

Growing experimental evidence has revealed the existence of programmed cell death (PCD) systems in bacteria. Among these is the mazEF system, which is a regulable suicide module located on the chromosome of E. coli and of some other bacteria, including pathogens. Several well-known antibiotics have recently been found to cause cell death in E. coli by indirectly activating this built-in suicide module. These antibiotics belong to two groups: (i) inhibitors of transcription and/or translation; and (ii) inhibitors of folic acid metabolism resulting in thymine starvation. These data, together with the recent elucidation of the crystal structure of mazEF-directed components, hold promise for a rational chemical design of a new class of antibiotics that directly activate chromosomal suicide modules by interacting with their components. Because multi-drug resistance among bacterial pathogens is becoming more widespread, the results obtained might be useful as a basis for producing alternative drugs.

Anti-Bacterial Agents↗
PubMed2004

Characterization of the novel Fusobacterium nucleatum plasmid pKH9 and evidence of an addiction system.

Fusobacterium nucleatum is an important oral anaerobic pathogen involved in periodontal and systemic infections. Studies of the molecular mechanisms involved in fusobacterial virulence and adhesion have been limited by lack of systems for efficient genetic manipulation. Plasmids were isolated from eight strains of F. nucleatum. The smallest plasmid, pKH9 (4,975 bp), was characterized and used to create new vectors for fusobacterial genetic manipulation. DNA sequence analysis of pKH9 revealed an open reading frame (ORF) encoding a putative autonomous rolling circle replication protein (Rep), an ORF predicted to encode a protein homologous to members of the FtsK/SpoIIIE cell division-DNA segregation protein family, and an operon encoding a putative toxin-antitoxin plasmid addiction system (txf-axf). Deletion analysis localized the pKH9 replication region in a 0.96-kbp fragment. The pKH9 rep gene is not present in this fragment, suggesting that pKH9 can replicate in fusobacteria independently of the Rep protein. A pKH9-based, compact Escherichia coli-F. nucleatum shuttle plasmid was constructed and found to be compatible with a previously described pFN1-based fusobacterial shuttle plasmid. Deletion of the pKH9 putative addiction system (txf-axf) reduced plasmid stability in fusobacteria, indicating its addiction properties and suggesting it to be the first plasmid addiction system described for fusobacteria. pKH9, its genetic elements, and its shuttle plasmid derivatives can serve as useful tools for investigating fusobacterial properties important in biofilm ecology and pathogenesis.

Amino Acid Motifs↗
PubMed2004

Escherichia coli mazEF-mediated cell death is triggered by various stressful conditions.

mazEF is an Escherichia coli suicide module specific for a stable toxin and a labile antitoxin. Inhibiting mazEF expression appeared to activate the module to cause cell death. Here we show that several stressful conditions, including high temperatures, DNA damage, and oxidative stress, also induce mazEF-mediated cell death. We also show that this process takes place only during logarithmic growth and requires an intact relA gene.

Cell Death↗