Chapter 3 : Life on the Inside: Microbial Strategies for Intracellular Survival and Persistence

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The strategies utilized by intracellular pathogens to propagate their genomes are discussed in this chapter in the context of recent developments in one's understanding of cell biology. The strategies employed by intracellular bacteria, defined by the establishment of replication-permissive niches, include (i) survival and replication within a phagolysosome , (ii) escape from the phagosome and replication within the cytoplasm, (iii) modulation of progression along the endocytic cascade, and (iv) exit from the endocytic cascade by entry into alternative pathways of membrane traffic within the host cell. The study of the cell biology of -containing vacuoles is in its infancy, but it does suggest differences among species. Interestingly, while avoiding interactions with the endocytic cascade, , , and some strains of display intimate interactions with other organelle systems, most notably the endoplasmic reticulum (ER) and mitochondria. The acquisition of the lysosomal marker LAMP, while bypassing the late-endosomal compartment, is explained by the localization of brucellae within vacuoles surrounded by the ER, identified by staining with Sec61β. In summary, the data suggest that -containing phagosomes exit the endocytic pathway and transit through the autophagous pathway en route to their replication-permissive niche, the ER. The study of the mechanisms by which the pathogens infect mammalian cells will undoubtedly yield fascinating insights into both microbiology and cell biology at the most intimate interface between the pathogen and host.

Citation: Sinai A. 2000. Life on the Inside: Microbial Strategies for Intracellular Survival and Persistence, p 31-51. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch3
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Image of FIGURE 1

Schematic representation of phagosomal maturation and the establishment of the phagolysosomal and cytoplasmic compartments as replication-permissive niches. FP, fluid phase; Lm, . See the text for a detailed description of these and other markers.

Citation: Sinai A. 2000. Life on the Inside: Microbial Strategies for Intracellular Survival and Persistence, p 31-51. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch3
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Image of FIGURE 2

Establishment of replication-permissive niches by modulation of the endocytic cascade. PM, plasma membrane; FP, fluid phase. See the text for a detailed description of these and other markers.

Citation: Sinai A. 2000. Life on the Inside: Microbial Strategies for Intracellular Survival and Persistence, p 31-51. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch3
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Image of FIGURE 3

Establishment of replication-permissive niches outside the endocytic cascade. PM, plasma membrane; Sm, sphingomyelin. See the text for a detailed description of these and other markers.

Citation: Sinai A. 2000. Life on the Inside: Microbial Strategies for Intracellular Survival and Persistence, p 31-51. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch3
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Image of FIGURE 4

Intracellular transport pathways coopted by bacterial pathogens. EE/ReE, early and recycling endosomes; LE, late endosome; PL, phagolysosome; TGN ,-Golgi network. See the text for a discussion.

Citation: Sinai A. 2000. Life on the Inside: Microbial Strategies for Intracellular Survival and Persistence, p 31-51. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch3
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