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Strategies Used by Bacteria to Grow in Macrophages

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  • Authors: Gabriel Mitchell*1, Chen Chen*3, Daniel A. Portnoy5
  • Editor: Siamon Gordon7
    Affiliations: 1: Department of Molecular and Cell Biology; 2: *Contributed equally to this work.; 3: Department of Molecular and Cell Biology; 4: *Contributed equally to this work.; 5: Department of Molecular and Cell Biology; 6: School of Public Health, University of California, Berkeley, Berkeley, CA 94720.; 7: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec May 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0012-2015
  • Received 28 May 2015 Accepted 03 September 2015 Published 06 May 2016
  • Daniel A. Portnoy, [email protected]
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  • Abstract:

    Intracellular bacteria are often clinically relevant pathogens that infect virtually every cell type found in host organisms. However, myeloid cells, especially macrophages, constitute the primary cells targeted by most species of intracellular bacteria. Paradoxically, macrophages possess an extensive antimicrobial arsenal and are efficient at killing microbes. In addition to their ability to detect and signal the presence of pathogens, macrophages sequester and digest microorganisms using the phagolysosomal and autophagy pathways or, ultimately, eliminate themselves through the induction of programmed cell death. Consequently, intracellular bacteria influence numerous host processes and deploy sophisticated strategies to replicate within these host cells. Although most intracellular bacteria have a unique intracellular life cycle, these pathogens are broadly categorized into intravacuolar and cytosolic bacteria. Following phagocytosis, intravacuolar bacteria reside in the host endomembrane system and, to some extent, are protected from the host cytosolic innate immune defenses. However, the intravacuolar lifestyle requires the generation and maintenance of unique specialized bacteria-containing vacuoles and involves a complex network of host-pathogen interactions. Conversely, cytosolic bacteria escape the phagolysosomal pathway and thrive in the nutrient-rich cytosol despite the presence of host cell-autonomous defenses. The understanding of host-pathogen interactions involved in the pathogenesis of intracellular bacteria will continue to provide mechanistic insights into basic cellular processes and may lead to the discovery of novel therapeutics targeting infectious and inflammatory diseases.

  • Citation: Mitchell* G, Chen* C, Portnoy D. 2016. Strategies Used by Bacteria to Grow in Macrophages. Microbiol Spectrum 4(3):MCHD-0012-2015. doi:10.1128/microbiolspec.MCHD-0012-2015.


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Intracellular bacteria are often clinically relevant pathogens that infect virtually every cell type found in host organisms. However, myeloid cells, especially macrophages, constitute the primary cells targeted by most species of intracellular bacteria. Paradoxically, macrophages possess an extensive antimicrobial arsenal and are efficient at killing microbes. In addition to their ability to detect and signal the presence of pathogens, macrophages sequester and digest microorganisms using the phagolysosomal and autophagy pathways or, ultimately, eliminate themselves through the induction of programmed cell death. Consequently, intracellular bacteria influence numerous host processes and deploy sophisticated strategies to replicate within these host cells. Although most intracellular bacteria have a unique intracellular life cycle, these pathogens are broadly categorized into intravacuolar and cytosolic bacteria. Following phagocytosis, intravacuolar bacteria reside in the host endomembrane system and, to some extent, are protected from the host cytosolic innate immune defenses. However, the intravacuolar lifestyle requires the generation and maintenance of unique specialized bacteria-containing vacuoles and involves a complex network of host-pathogen interactions. Conversely, cytosolic bacteria escape the phagolysosomal pathway and thrive in the nutrient-rich cytosol despite the presence of host cell-autonomous defenses. The understanding of host-pathogen interactions involved in the pathogenesis of intracellular bacteria will continue to provide mechanistic insights into basic cellular processes and may lead to the discovery of novel therapeutics targeting infectious and inflammatory diseases.

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Lifestyles of intracellular bacterial pathogens. (1) escapes a late endosome (LE)-like vacuole in a T6SS-dependent manner. Following replication in the cytosol, may retranslocate to a membrane-bound compartment resembling an autolysosome. (2) escapes the phagolysosomal pathway using the T2SS (Sec) effectors LLO and PLCs. replicates rapidly in the cytosol and hijacks the host actin polymerization machinery to move within and between cells. (3) escapes into the cytosol in a T3SS-dependent manner. performs actin-based motility and promotes host cell fusion. (4) is adapted to the phagolysosomal pathway and resides in a spacious phagolysosomal-like compartment. The Dot/Icm system (T4SS) is required for recruiting the autophagosomal marker LC3 and for vacuole biogenesis. (5) arrests phagosome maturation at the early endosome (EE) stage in a T7SS-dependent manner. (6) and segregate from the endocytic route at the EE stage, recruit ER-derived vesicles, and form ribosome-studded specialized vacuoles in a T4SS-dependent manner. (7) e segregates from the endocytic route and forms a unique inclusion vacuole by recruiting Golgi-derived vesicles. e effectors promote Golgi fragmentation and generate actin filaments around the inclusion. is found in two different forms: the nonreplicating infectious elementary body (EB) and the intracytoplasmic replicative reticulate body (RB). T2SS and T3SS effectors are thought to be involved in the intracellular life cycle of . (8) replicates in an LE-like compartment that excludes lysosomal degradation enzymes. The -containing vacuole migrates to the microtubule-organizing center and forms -induced filaments (Sif) along microtubules in a T3SS-dependent manner.

Source: microbiolspec May 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0012-2015
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Characteristics and diseases associated with intracellular pathogens that infect human myeloid cells

Source: microbiolspec May 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0012-2015
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General strategies used by intravacuolar and cytosolic bacteria to deal with challenges encountered within host cells

Source: microbiolspec May 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0012-2015
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Examples of factors used by intracellular bacteria to counteract host defense mechanisms

Source: microbiolspec May 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0012-2015

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