I. BACTERIAL PATHOGENESIS

C. VIRULENCE FACTORS THAT DAMAGE THE HOST

2. Producing Harmful Exotoxins

b. Type II Toxins: Exotoxins that Damage Host Cell Membranes

Fundamental Statements for this Learning Object:

1. Type II toxins are typically phospholipases or pore-forming cytotoxins that disrupt the integrity of eukaryotic cell membranes.
2. Damages host cells release danger-associated molecular patterns (DAMPs) that bind to pattern-recognition receptors (PRRs) causing the release of inflammatory cytokines. This inflammatory response can also further contribute to tissue damage.
3. Examples include the exotoxins of
Clostridium perfringens that cause gas gangrene, exotoxins of Pseudomonas aeruginosa that causes a variety of opportunistic infections, exotoxins of Streptococcus pyogenes that causes strep throat, the exotoxins of Clostridium difficile that causes antibiotic-associated colitis, and leukotoxins, pore-forming toxins that
causes lysis of white blood cells.

 

LEARNING OBJECTIVES FOR THIS SECTION


In this section on Bacterial Pathogenesis we are looking at virulence factors that damage the host. Virulence factors that damage the host include:

1. The ability to produce Pathogen-Associated Molecular Patterns or PAMPs that bind to host cells causing them to synthesize and secrete inflammatory cytokines and chemokines;

2. The ability to produce harmful exotoxins.

3. The ability to induce autoimmune responses.

We are currently looking at the ability of bacteria to produce harmful exotoxins.

Exotoxins (def) are toxins, often proteins in nature, secreted from a living bacterium but also released upon bacterial lysis. In addition, some bacteria use a type 3 secretion system or a type 4 secretion system to inject toxins directly into human cells. There are three main types of exotoxins:

1. superantigens (Type I toxins),

2. exotoxins that damage host cell membranes (Type II toxins)

3. A-B toxins and other toxin that interfere with host cell function (Type II I toxins).

We will now look at exotoxins that damage host cell membranes.


The Ability to Produce Harmful Exotoxins

b. Type II Toxins: Toxins that Damage Host Cell Membranes

Type II toxins are typically phospholipases or pore-forming cytotoxins that disrupt the integrity of eukaryotic cell membranes. Damages host cells release danger-associated molecular patterns (DAMPs) (def) that bind to pattern-recognition receptors (PRRs) causing the release of inflammatory cytokines. This inflammatory response can also further contribute to tissue damage.

1. The exotoxins of Clostridium perfringens (inf). This bacterium produces at least 20 exotoxins that play a role in the pathogenesis of gas gangrene and producing expanding zones of dead tissue (necrosis) surrounding the bacteria. Toxins include:

A major characteristic of gas gangrene is the ability of C. perfringens to very rapidly spread from the initial wound site leaving behind an expanding zone of dead tissue. This organism spreads as a result of the pressure from fluid accumulation (due to increased capillary permeability from alpha toxin) and gas production (anaerobic fermentation of glucose by the organisms produces hydrogen and carbon dioxide), coupled with the breakdown of surrounding connective tissue (kappa toxin) and tissue cement (mu toxin).


Highlighted Bacterium:
Clostridioides difficile

Click on this link, read the description of Clostridioides difficile (formerly known as Clostridium difficile), and be able to match the bacterium with its description on an exam.

 

7. Bordetella tracheal cytotoxin, produced by Bordetella pertussis (inf), causes the respiratory cell damage during whooping cough. Cell death, inhibition of ciliary movement by ciliated epithelial cells, and release of the inflammatory cytokine IL-1 triggers the violent coughing episodes, the only way the body can now remove inflammatory debris, bacteria, and mucus.

 

As mentioned earlier in this unit, many bacteria are able to sense their own population density, communicate with each other by way of secreted chemical factors, and behave as a population rather than as individual bacteria . This is referred to as cell-to-cell signaling or quorum sensing and plays an important role in pathogenicity and survival for many bacteria.

Quorum sensing involves the production, release, and community-wide sensing of molecules called autoinducers that modulate gene expression in response to the density of a bacterial population. When autoinducers produced by one bacterium cross the membrane of another, they bind to receptors in the cytoplasm. This autoinducer/receptor complex is then able to bind to DNA promoters and activate the transcription of quorum sensing-controlled genes. In this way, individual bacteria within a group are able to benefit from the activity of the entire group.

The outcomes of bacteria-host interaction are often related to bacterial population density. Bacterial virulence, that is its ability to cause disease, is largely based on the bacterium's ability to produce gene products called virulence factors that enable that bacterium to colonize the host, resist body defenses, and harm the body. If a relatively small number of a specific bacteria were to enter the body and immediately start producing their virulence factors, chances are the body's immune systems would have sufficient time to recognize and counter those virulence factors and remove the bacteria before there was sufficient quantity to cause harm. Many bacteria are able to delay production of those virulence factors by not expressing the genes for those factors until there is a sufficiently large enough population of that bacterium (a quorum). As the bacteria geometrically increase in number, so does the amount of their secreted autoinducers.

When a critical level of autoinducer is reached, the entire population of bacteria is able to simultaneously activate the transcription of their quorum-sensing genes and the body's immune systems are much less likely to have enough time to counter those virulence factors before harm is done.

Medscape article on infections associated with organisms mentioned in this Learning Object. Registration to access this website is free.

 

Concept map for Type II Toxins (Toxins that Damage Membranes).

 

 

Gary E. Kaiser, Ph.D.
Professor of Microbiology
The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work at http://faculty.ccbcmd.edu/~gkaiser/index.html.

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Last updated: August, 2019
Please send comments and inquiries to Dr. Gary Kaiser