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Chapter 1 : Bacterial Adherence, Colonization, and Invasion of Mucosal Surfaces

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Abstract:

This chapter provides a brief overview of the pathogenic strategies of some bacteria that infect the mucosal surface of the intestinal tract. It focuses on two model systems for the study of bacterial pathogens that cause disease by colonizing (enteropathogenic [EPEC]) or penetrating ( species) the intestinal epithelium. Mucosal surfaces have many physiological defenses against pathogenic bacteria. These include entrapment in a thick blanket of mucus and clearance by peristalsis in the gut or ciliary movement in the airways. Adhesins on the bacterial surface provide specificity for interaction with target host cells. For example, M cells of the intestinal epithelium have cell surface glycosylation patterns that vary between species and tissue location. Adhesion is often a prerequisite for penetration of the mucosal surface, though different pathogens penetrate this barrier by different means and with different ends. EPEC provides a suitable model for understanding A/E pathogens and has largely been studied in vitro by infection of epithelial tissue cell cultures. species infect a broad range of animals and can cause different diseases in different hosts. For example serovar Typhi causes typhoid fever in humans, which can be fatal. Recent progress has revealed the mechanisms by which the translocated effectors of SPI-1 mediate invasion by serovar Typhimurium. Pathogenic bacteria have evolved different strategies to initiate infection at mucosal surfaces.

Citation: Brumell J, Finlay B. 2000. Bacterial Adherence, Colonization, and Invasion of Mucosal Surfaces, p 3-17. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch1

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Type III Secretion System
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FIGURE 1

Type III secretion systems of EPEC and serovar Typhimurium. Depicted are the needle-like complexes ( ) that span both bacterial membranes of the pathogen and deliver translocated effector proteins into the host cell. These effector proteins can then manipulate host signaling systems. Note that serovar Typhimurium express two type III secretion systems: one that delivers effectors across the plasma membrane (encoded within SPI-1) to mediate invasion (see text), and a separate system that mediates survival and replication within host cells (SPI-2) by delivering effector proteins across the membrane of the SCV. Artwork provided by A. Gauthier.

Citation: Brumell J, Finlay B. 2000. Bacterial Adherence, Colonization, and Invasion of Mucosal Surfaces, p 3-17. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch1
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Image of FIGURE 2
FIGURE 2

Models of EPEC pathogenesis. (A) Formation of pedestals by EPEC on the surface of HeLa epithelial cells in vitro. Scanning electron micrograph provided by Dr. I. Rosenshine. (B) Formation of A/E lesions in vivo by REPEC 0103. Pedestal formation on the intestinal surface is indicated with arrows. Note that on these cells, effacement of microvilli has occurred (compare to upper right hand side). TEM provided by Dr. U. Heczko and reproduced from , 1998, volume 188, pages 1907–1916 ( ) by copyright permission of the Rockefeller University Press. (C) Three-stage model of EPEC pedestal formation. In the first step, attachment of EPEC is mediated by bundle-forming pilus (BFP) binding to the epithelial cell surface. Next, the type III secretion system mediates delivery of both Esp's and the Tir. Intiminindependent host signals are activated and Tir is phosphorylated by an unknown tyrosine kinase. Finally, intimin binding mediates clustering of phosphorylated Tir, intimin-dependent host signals are activated, and rearrangements of the host actin cytoskeleton cause pedestal formation. Artwork provided by Dr. R. DeVinney and reprinted from , volume 2, pages 83–88, copyright 1999 ( ), with permission from Elsevier Science.

Citation: Brumell J, Finlay B. 2000. Bacterial Adherence, Colonization, and Invasion of Mucosal Surfaces, p 3-17. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch1
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Image of FIGURE 3
FIGURE 3

Models of serovar Typhimurium pathogenesis. (A) Cell-surface ruffling of Caco-2 epithelial cells induced by serovar Typhimurium. Note the loss of microvilli near bacteria and the formation of large ruffles. (B) Uptake of serovar Typhimurium in large vacuoles that resemble macropinosomes in vitro. (C) Invasion of epithelial cells by delivery of translocated effectors into the host cell. Depicted are the translocated effectors of the SPI-1-encoded type III secretion system and the host signaling systems that they directly interact with. These effectors have numerous effects on the host cell, including ruffling of the cell surface (thereby directing serovar Typhimurium uptake), production of proinflammatory cytokines, and apoptosis. Artwork modified from ( ) with permission from Elsevier Science. (D) Intracellular trafficking of serovar Typhimurium in host cells. Upon entry into host cells, serovar Typhimurium remain in a vacuolar compartment (SCV) that interacts transiently with early endosomes. However, these vacuoles do not undergo further processing within the endosomal system and do not fuse with mature lysosomes. Instead, the SCV appear to interact with an unknown compartment that mediates delivery of lysosomal glycoproteins (such as LAMP-1) but not degradative lysosomal enzymes such as cathepsin D ( ). After several hours, intracellular serovar Typhimurium begins to replicate and long, contiguous tubules (Sifs) are formed. Artwork provided by O. Steele-Mortimer and modified from ( ) with permission from Blackwell Science Ltd.

Citation: Brumell J, Finlay B. 2000. Bacterial Adherence, Colonization, and Invasion of Mucosal Surfaces, p 3-17. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch1
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