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Pathogenesis: New Insights through Advanced Methodologies

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • Authors: Pamela Schnupf1, Philippe J. Sansonetti2
  • Editors: Pascale Cossart3, Craig R. Roy4, Philippe Sansonetti5
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Institut Imagine, Laboratory of Intestinal Immunity, INSERM UMR1163; Institut Necker Enfants Malades, Laboratory of Host-Microbiota Interaction, INSERM U1151; and Université Paris Descartes-Sorbonne, 75006 Paris, France; 2: Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire, INSERM U1202, and College de France, Paris, France; 3: Institut Pasteur, Paris, France; 4: Yale University School of Medicine, New Haven, Connecticut; 5: Institut Pasteur, Paris, France
  • Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0023-2019
  • Received 17 January 2019 Accepted 15 February 2019 Published 12 April 2019
  • Pamela Schnupf, [email protected]; Philippe J. Sansonetti, [email protected]
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  • Abstract:

    is a genus of Gram-negative enteropathogens that have long been, and continue to be, an important public health concern worldwide. Over the past several decades, spp. have also served as model pathogens in the study of bacterial pathogenesis, and has become one of the best-studied pathogens on a molecular, cellular, and tissue level. In the arms race between and the host immune system, has developed highly sophisticated mechanisms to subvert host cell processes in order to promote infection, escape immune detection, and prevent bacterial clearance. Here, we give an overview of pathogenesis while highlighting innovative techniques and methods whose application has significantly advanced our understanding of pathogenesis in recent years.

  • Citation: Schnupf P, Sansonetti P. 2019. Pathogenesis: New Insights through Advanced Methodologies. Microbiol Spectrum 7(2):BAI-0023-2019. doi:10.1128/microbiolspec.BAI-0023-2019.

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/content/journal/microbiolspec/10.1128/microbiolspec.BAI-0023-2019
2019-04-12
2019-10-22

Abstract:

is a genus of Gram-negative enteropathogens that have long been, and continue to be, an important public health concern worldwide. Over the past several decades, spp. have also served as model pathogens in the study of bacterial pathogenesis, and has become one of the best-studied pathogens on a molecular, cellular, and tissue level. In the arms race between and the host immune system, has developed highly sophisticated mechanisms to subvert host cell processes in order to promote infection, escape immune detection, and prevent bacterial clearance. Here, we give an overview of pathogenesis while highlighting innovative techniques and methods whose application has significantly advanced our understanding of pathogenesis in recent years.

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Image of FIGURE 1
FIGURE 1

pathogenesis. infects the colonic epithelium at the follicle-associated epithelium and near the opening of colonic crypts. Invasion of M cells leads to transcytosis and release of at the basolateral side of the epithelium. can be taken up by macrophages and dendritic cells, which subsequently undergo pyroptosis, stimulating inflammation through the release of IL-1β and IL-18, which recruit neutrophils and activate innate defenses. also efficiently invades the basolateral side of the colonic epithelium from the lamina propria to reach its major replicative niche and the epithelial cell cytosol and propagate infection through cell-to-cell spread.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0023-2019
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FIGURE 2

T3SS and effectors. () Expression of the T3SS apparatus and its effectors is regulated by a number of environmental factors that, through the transcription factor VirF, control the expression of the transcription factor VirB, which controls the expression of the T3SS apparatus and the first wave of effectors. Upon activation of the T3SS apparatus, MxiE is released from its inhibition and stimulates the transcription of the second wave of effectors. () When the T3SS is closed, first-wave effectors are stored in the bacterial cytoplasm with or without chaperones, while the gatekeeper MxiC and the translocator proteins IpaB and IpaD at the T3SS tip prevent effector secretion. Upon activation of the T3SS, effectors are secreted into the host cell cytosol, and expression of second-wave effectors is mediated by MxiE in complex with IpgC. IM, inner membrane; OM, outer membrane; PM, plasma membrane.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0023-2019
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FIGURE 3

subversion of host cell survival, integrity, and function. produces numerous effectors that subvert various host cell processes to promote its virulence. Upon invasion of epithelial cells, numerous effectors function to protect the cytosolic replicative niche of by antagonizing host cell death (apoptosis, pyroptosis, and necrosis), promoting host cell integrity, and inhibiting the recruitment of neutrophils, which kill . Conversely, actively promotes host cell death in infected macrophages. For immune cells, mediates B cell death and the inhibition of T cell migration in infected and noninfected cells.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0023-2019
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FIGURE 4

modulation of antimicrobial defenses and proinflammatory responses. () Numerous effectors have been linked to the evasion of autophagy during cytosolic growth and cell-to-cell spread to foster bacterial survival and propagation. The presence, replication, and spreading of are sensed by the cellular immune surveillance system of the host, which is linked to proinflammatory responses. actively counteracts the cellular proinflammatory response in epithelial cells through inhibition of key signaling pathways () and disruption of the vesicular trafficking pathways ().

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0023-2019
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