Multifaceted Interactions of Bacterial Toxins With the Gastrointestinal Mucosa

MR Popoff

Disclosures

Future Microbiol. 2011;6(7):763-797. 

In This Article

Abstract and Introduction

Abstract

The digestive tract is one of the ecosystems that harbors the largest number and greatest variety of bacteria. Among them, certain bacteria have developed various strategies, including the synthesis of virulence factors such as toxins, to interact with the intestinal mucosa, and are responsible for various pathologies. A large variety of bacterial toxins of different sizes, structures and modes of action are able to interact with the gastrointestinal mucosa. Some toxins, termed enterotoxins, directly stimulate fluid secretion in enterocytes or cause their death, whereas other toxins pass through the intestinal barrier and disseminate by the general circulation to remote organs or tissues, where they are active. After recognition of a membrane receptor on target cells, toxins can act at the cell membrane by transducing a signal across the membrane in a hormone-like manner, by pore formation or by damaging membrane compounds. Other toxins can enter the cells and modify an intracellular target leading to a disregulation of certain physiological processes or disorganization of some structural architectures and cell death. Toxins are fascinating molecules, which mimic or interfere with eukaryotic physiological processes. Thereby, they have permitted the identification and characterization of new natural hormones or regulatory pathways. Besides use as protective antigens in vaccines, toxins offer multiple possibilities in pharmacology, such as immune modulation or specific delivery of a protein of interest into target cells.

Introduction

The intestinal tract constitutes the largest mucosal surface of the body. It is directly exposed to the external environment and, thus, susceptible to colonization and invasion by various and multiple microorganisms. Indeed, the intestinal ecosystem is one of the most densely populated microbial habitats. For example, a very high density and diversity of bacteria can be found in the human intestinal tract, up to 1011–1012 microbes per ml of luminal content.[1,2] Microbiota have multiple functions in the host, such as nutrient processing, immune system development, stimulation of angiogenesis, regulation of host fat storage and the resident microflora contributes significantly to the prevention of colonization by intruding pathogens. Thus, changes in microbiota composition have important consequences in disruption of colonization resistance and enhancement of pathogen growth.[3] Intestinal epithelial cells surrounded by a mucus layer form a barrier that separates the external environment from the underlying tissues and has critical functions, including nutrient transport, water and electrolyte exchanges, endocrine and paracrine hormone production, as well as protection against invasion and systemic dissemination of both pathogenic and commensal microorganisms.[4] A complex crosstalk between the gut microbiota and the intestinal mucosa, mainly mediated by the production of antimicrobial peptides and control of the gastrointestinal inflammatory response, has an essential role in the stabilization of microbiota composition and in the prevention of intruding pathogen growth.[3] However, epithelial cells are also the target of various bacterial virulence factors, such as bacterial attachment factors and toxins, permitting mucosal colonization and/or invasion, as well as cell alteration by enteropathogens. Toxins are secreted by bacteria in the external medium and can act at distance from the bacterial colonization site. They represent one of the most potent mechanism of pathogenicity. Toxins that specifically interact with intestinal cells, are called enterotoxins. In contast to toxigenic bacteria, invasive bacteria directly inject virulence factors into target cells, mainly through a type III secretion system, which permits the invasion process and bacterial survival within cells. Some type III virulence factors share common modes of activity with secreted toxins, but they exert their toxicity only in cells targeted by the bacteria. This article focuses on bacterial toxins interacting with the gastrointestinal mucosa based on their different molecular modes of activity and effects induced in the host.

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