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501.
502.
Chantal de Chastellier Frédérique Forquet Alon Gordon Lutz Thilo 《Cellular microbiology》2009,11(8):1190-1207
Pathogenic mycobacteria survive in macrophages of the host organism by residing in phagosomes which they prevent from undergoing maturation and fusion with lysosomes. Several molecular mechanisms have been associated with the phagosome maturation block. Here we show for Mycobacterium avium in mouse bone marrow-derived macrophages that the maturation block required an all-around close apposition between the mycobacterial surface and the phagosome membrane. When small (0.1 μm) latex beads were covalently attached to the mycobacterial surface to act as a spacer that interfered with a close apposition, phagosomes rapidly acquired lysosomal characteristics as indicators for maturation and fusion with lysosomes. As a result, several mycobacteria were delivered into single phagolysosomes. Detailed electron-microscope observations of phagosome morphology over a 7-day post-infection period showed a linear correlation between bead attachment and phagosome–lysosome fusion. After about 3 days post infection, conditions inside phagolysosomes caused a gradual release of beads. This allowed mycobacteria to re-establish a close apposition with the surrounding membrane and sequester themselves into individual, non-maturing phagosomes which had lost lysosomal characteristics. By rescuing themselves from phagolysosomes, mycobacteria remained fully viable and able to multiply at the normal rate. In order to unify the present observations and previously reported mechanisms for the maturation block, we discuss evidence that they may act synergistically to interfere with 'Phagosome Membrane Economics' by causing relative changes in incoming and outgoing endocytic membrane fluxes. 相似文献
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R Simons N Alon J R Riordan 《Biochemical and biophysical research communications》1987,146(2):666-671
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Won Dong Lee Anna Chiara Pirona Boris Sarvin Alon Stern Keren Nevo-Dinur Elazar Besser Nikita Sarvin Shoval Lagziel Dzmitry Mukha Shachar Raz Elina Aizenshtein Tomer Shlomi 《Cell metabolism》2021,33(1):190-198.e6
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506.
The Diastoporidan colony consists of three zones: The marginal common bud, a narrow middle zone with erect peristomes and active polypides nourishing the whole colony, and a large central zone where the erect peristomes are detached, the secondary orifices thus formed are closed by terminal diaphragms, and the feeding polypides have degenerated. In many Diastoporidae the terminal closure is complete, but in several species the diaphragm is raised into a narrow, open tubule. In the latter type a dwarfed polypide with one tentacle only is regenerated: The autozooid is transformed into a heterozooid (“secondary nanozooid”), a unique phenomenon. Its function is unknown. The single tentacle of the “true nanozooids” of Diplosolen performs sweeping movements indicating a cleaning function. In two Plagioecia species “occasional nanozooids” were found, induced by disturbances of the colony growth. The function, if any, is unknown. 相似文献
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Rachel Yamin Noa S. Kaynan Ariella Glasner Alon Vitenshtein Pinchas Tsukerman Yoav Bauman Yael Ophir Shlomo Elias Yotam Bar-On Chamutal Gur Ofer Mandelboim 《PLoS pathogens》2013,9(8)
Natural killer (NK) cells are innate immune cells able to rapidly kill virus-infected and tumor cells. Two NK cell populations are found in the blood; the majority (90%) expresses the CD16 receptor and also express the CD56 protein in intermediate levels (CD56Dim CD16Pos) while the remaining 10% are CD16 negative and express CD56 in high levels (CD56Bright CD16Neg). NK cells also reside in some tissues and traffic to various infected organs through the usage of different chemokines and chemokine receptors. Kaposi''s sarcoma-associated herpesvirus (KSHV) is a human virus that has developed numerous sophisticated and versatile strategies to escape the attack of immune cells such as NK cells. Here, we investigate whether the KSHV derived cytokine (vIL-6) and chemokines (vMIP-I, vMIP-II, vMIP-III) affect NK cell activity. Using transwell migration assays, KSHV infected cells, as well as fusion and recombinant proteins, we show that out of the four cytokine/chemokines encoded by KSHV, vMIP-II is the only one that binds to the majority of NK cells, affecting their migration. We demonstrate that vMIP-II binds to two different receptors, CX3CR1 and CCR5, expressed by naïve CD56Dim CD16Pos NK cells and activated NK cells, respectively. Furthermore, we show that the binding of vMIP-II to CX3CR1 and CCR5 blocks the binding of the natural ligands of these receptors, Fractalkine (Fck) and RANTES, respectively. Finally, we show that vMIP-II inhibits the migration of naïve and activated NK cells towards Fck and RANTES. Thus, we present here a novel mechanism in which KSHV uses a unique protein that antagonizes the activity of two distinct chemokine receptors to inhibit the migration of naïve and activated NK cells. 相似文献
508.
Awareness of the problem of antimicrobial resistance (AMR) has escalated and drug-resistant infections are named among the most urgent problems facing clinicians today. Our experiments here identify a transporter interactome and portray its essential function in acquisition of antimicrobial resistance. By exposing E. coli cells to consecutive increasing concentrations of the fluoroquinolone norfloxacin we generated in the laboratory highly resistant strains that carry multiple mutations, most of them identical to those identified in clinical isolates. With this experimental paradigm, we show that the MDTs function in a coordinated mode to provide an essential first-line defense mechanism, preventing the drug reaching lethal concentrations, until a number of stable efficient alterations occur that allow survival. Single-component efflux transporters remove the toxic compounds from the cytoplasm to the periplasmic space where TolC-dependent transporters expel them from the cell. We postulate a close interaction between the two types of transporters to prevent rapid leak of the hydrophobic substrates back into the cell. The findings change the prevalent concept that in Gram-negative bacteria a single multidrug transporter, AcrAB-TolC type, is responsible for the resistance. The concept of a functional interactome, the process of identification of its members, the elucidation of the nature of the interactions and its role in cell physiology will change the existing paradigms in the field. We anticipate that our work will have an impact on the present strategy searching for inhibitors of AcrAB-TolC as adjuvants of existing antibiotics and provide novel targets for this urgent undertaking. 相似文献
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Jung Carina M. Carr Matthew Blakeney G. Alon Indest Karl J. 《Journal of industrial microbiology & biotechnology》2019,46(9-10):1273-1281
Journal of Industrial Microbiology & Biotechnology - Horizontal gene transfer (HGT) is the lateral movement of genetic material between organisms. The RDX explosive-degrading bacterium Gordonia... 相似文献