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One example of a protease that contains a metal ion is the exoenzyme collagenase . Collagenase digests collagen, the dominant protein in connective tissue. Collagen can be found in the extracellular matrix, especially near mucosal membranes, blood vessels, nerves, and in the layers of the skin. Similar to hyaluronidase, collagenase allows the pathogen to penetrate and spread through the host tissue by digesting this connective tissue protein. The collagenase produced by the gram-positive bacterium Clostridium perfringens , for example, allows the bacterium to make its way through the tissue layers and subsequently enter and multiply in the blood (septicemia). C. perfringens then uses toxins and a phospholipase to cause cellular lysis and necrosis. Once the host cells have died, the bacterium produces gas by fermenting the muscle carbohydrates. The widespread necrosis of tissue and accompanying gas are characteristic of the condition known as gas gangrene ( [link] ).

A diagram of a tube labeled lumen of blood vessel lined by cells labeled endothelial cells. Outside he cells is dense irregular connective tissue. Collagenase is shown as small dots that break up the connections between the cells. A micrograph of the dense connective tissue shows many red lines making a meshwork.
The illustration depicts a blood vessel with a single layer of endothelial cells surrounding the lumen and dense connective tissue (shown in red) surrounding the endothelial cell layer. Collagenase produced by C. perfringens degrades the collagen between the endothelial cells, allowing the bacteria to enter the bloodstream. (credit illustration: modification of work by Bruce Blaus; credit micrograph: Micrograph provided by the Regents of University of Michigan Medical School © 2012)

Toxins

In addition to exoenzymes, certain pathogens are able to produce toxin s , biological poisons that assist in their ability to invade and cause damage to tissues. The ability of a pathogen to produce toxins to cause damage to host cells is called toxigenicity .

Toxins can be categorized as endotoxins or exotoxins. The lipopolysaccharide (LPS) found on the outer membrane of gram-negative bacteria is called endotoxin ( [link] ). During infection and disease, gram-negative bacterial pathogens release endotoxin either when the cell dies, resulting in the disintegration of the membrane, or when the bacterium undergoes binary fission. The lipid component of endotoxin, lipid A , is responsible for the toxic properties of the LPS molecule. Lipid A is relatively conserved across different genera of gram-negative bacteria; therefore, the toxic properties of lipid A are similar regardless of the gram-negative pathogen. In a manner similar to that of tumor necrosis factor, lipid A triggers the immune system’s inflammatory response (see Inflammation and Fever ). If the concentration of endotoxin in the body is low, the inflammatory response may provide the host an effective defense against infection; on the other hand, high concentrations of endotoxin in the blood can cause an excessive inflammatory response, leading to a severe drop in blood pressure, multi-organ failure, and death.

A long chain of O antigens is drawn as various geometric shapes in a long row. Next is a core; a shorter region of similar shapes. Next is 2 circles labeled lipid A. Each of these has 2 or 3 long wavy lines projecting from them.
Lipopolysaccharide is composed of lipid A, a core glycolipid, and an O-specific polysaccharide side chain. Lipid A is the toxic component that promotes inflammation and fever.

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Source:  OpenStax, Microbiology. OpenStax CNX. Nov 01, 2016 Download for free at http://cnx.org/content/col12087/1.4
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