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Biomedical subjects

K T McCusker

Publications and source records attributed to K T McCusker.

5 recordsLinked to original sources

Legionella pneumophila inhibits protein synthesis in Chinese hamster ovary cells.

Legionella pneumophila is a gram-negative facultative intracellular parasite that causes Legionnaires disease. To explore the interactions between L. pneumophila and host cells, we have developed a continuous cell line model of infection. We show that about 80% of Chinese hamster ovary (CHO) cells were associated with L. pneumophila after incubation for 3 h at a multiplicity of infection of 20 bacteria per cell. Within 3 to 4 h of incubation with L. pneumophila, protein synthesis of CHO cells was markedly inhibited, as shown by the reduction of incorporation of radiolabeled amino acids into proteins. L. pneumophila did not inhibit transport of amino acids or cause degradation of newly synthesized proteins in CHO cells. Cytochalasin D blocked internalization of L. pneumophila by CHO cells, yet CHO cell protein synthesis was inhibited. These results indicated that L. pneumophila could inhibit host protein synthesis from the cell exterior. L. pneumophila that had been killed with antibiotics prior to incubation with CHO cells still inhibited protein synthesis, indicating that the inhibition of CHO cell protein synthesis occurred in the absence of de novo protein synthesis by L. pneumophila.

Animals

Legionella pneumophila: denizen of defenders.

Legionella pneumophila, the causative agent of legionellosis, is an intracellular parasite of human monocytic cells and neutrophils. The life cycle of Legionella within phagocytic cells is distinct from that of other bacterial pathogens. Adherence of L pneumophila to phagocytes is mediated by attachment of complement proteins to the Legionella cell surface, followed by binding to complement receptors of phagocytes. Opsonized Legionella also may enter phagocytes after engagement of the Fc receptors. Within the host cell, the parasites reside in a membrane-bound vacuole that does not fuse with lysosomes. Activation of mononuclear phagocytes by the cell-mediated immune system serves to limit intracellular bacterial growth. Polymorphonuclear leukocytes are better at killing L pneumophila than are macrophages. However, Legionella also can invade and parasitize granulocytes. Although significant progress has been made in understanding some aspects of the pathogenesis of legionellosis, we know very little about the mechanisms by which these facultative intracellular parasites avoid killing by host defense mechanisms. This is an important area for future research and should lead to a better understanding of host-parasite interactions.

Bacterial Adhesion