C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/12 (2006.01) C07K 14/22 (2006.01) C07K 14/47 (2006.01) C07K 16/12 (2006.01) C07K 16/18 (2006.01) C12Q 1/00 (2006.01) C12Q 1/18 (2006.01)
Patent
CA 2308260
Min proteins are involved in cell division site selection in bacteria. Using Neisseria gonorrhoeae as a model to study the role of Min proteins, a min cluster containing homologues of minC, minD and minE was identified. N. gonorrhoeae (Ng) CH811 minC and minD insertional mutants exhibited aberrant division patterns, in some cases producing burst cells, indicating that cell division site selection was disrupted. These mutants also presented delayed growth and altered viability. When gonococcal min genes were expressed individually, as a cluster, or as fusions to green fluorescent protein (GFP) in E. coli PB103, minicells and/or filaments were produced, indicating that these min genes disrupt cell division in other genera and that they are ubiquitous cell division inhibitors. The appearance of filamentous E. coli cells expressing MinC Ng and GFP-MinC Ng, and the polar localization of GFP- MinC Ng in E. coli supports the role for MinC Ng as a cell division inhibitor. In addition, in round E. coli cells (i.e. rodA mutants), which divide in alternating perpendicular planes as does N. gonorrhoeae, MinC overexpression induced gross enlargement of the cells leading, in some cases, to bursting. GFP-MinD Ng and MinE Ng GFP were both distributed throughout the E. coli cells, although MinE Ng- GFP was more concentrated at the cell poles. Novel Min Ng - Min Ng interactions were observed using yeast two-hybrid assays, especially the MinD Ng self- interaction. As reported herein, various Min proteins are conserved between a large number of bacteria genera, and are required for proper bacterial cell division. Important to the present invention is the finding that MinC and MinE proteins have no counterparts in humans and MinD only resembles human proteins at its ATP-binding site. Thus, the Min proteins and/or their corresponding DNA sequences provide a novel therapeutic target for the development of antibacterial agents.
Dillon Jo-Anne R.
Ramirez-Arcos Sandra
Salimnia Hossein
Szeto Jason
Dillon Jo-Anne R.
Gowling Lafleur Henderson Llp
Ramirez-Arcos Sandra
Salimnia Hossein
Szeto Jason
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