I. BACTERIAL PATHOGENESIS
B. VIRULENCE FACTORS THAT PROMOTE BACTERIAL COLONIZATION OF THE HOST
1. The ability to use motility or other means to contact host cells
Fundamental Statements for this Learning Object:
1. Bacteria have to make physical contact with host cells before they can adhere to those cells and resist being flushed out of the body.
2. Motile bacteria can use their flagella and chemotaxis to swim through mucus towards mucosal epithelial cells.
3. Because of their thinness, their internal flagella (axial filaments), their corkscrew shape, and their motility, certain spirochetes are more readily able enter lymph vessels and blood vessels and spread to other body sites.
4. Many bacteria produce enzymes that degrade the extracellular matrix proteins that surround cells and tissues and help to localize infection, making it easier for those bacteria to spread within the body.
5. Some bacteria produce toxins that induce diarrhea in the host enabling the pathogen to more readily leave one host and enter new hosts through the fecal-oral route.
LEARNING OBJECTIVES FOR THIS SECTION
In this section on Bacterial Pathogenesis we are looking at virulence factors that promote bacterial colonization of the host. The following are virulence factors that promote bacterial colonization of the host .
1. The ability to use motility and other means to contact host cells and disseminate within a host.
2. The ability to adhere to host cells and resist physical removal.
3. The ability to invade host cells.
4. The ability to compete for iron and other nutrients.
5. The ability to resist innate immune defenses such as phagocytosis and complement.
6. The ability to evade adaptive immune defenses.
We will now look at virulence factors (def) that enable bacteria to contact host cells.
Virulence Factors that Promote Bacterial Colonization of the Host
1. The Ability to Use Motility or Other Means to Contact Host Cells and Disseminate Within a Host
The mucosal surfaces of the respiratory tract, the intestinal tract, and the genitourinary tract constantly flush bacteria away in order to prevent colonization of host mucous membranes. Motile bacteria can use their motility and chemotaxis to swim through mucus towards mucosal epithelial cells. Many bacteria that can colonize the mucous membranes of the bladder and the intestines, in fact, are motile. Motility probably helps these bacteria move through the mucus between the mucin strands or in places where the mucus is less viscous. Examples of motile opportunists and pathogens include Helicobacter pylori, Salmonella species, Escherichia coli, Pseudomonas aeruginosa, and Vibrio cholerae.
Once bacteria contact host cells they can subsequently attach, and colonize. (Attachment will be discussed in the next section.)
You Tube animation showing Pseudomonas using motility, pili, and exotoxins to cause an infection.
3D Medical Animations Library and Downloads, www.rufusrajadurai. wetpaint.com
Movie of motile Escherichia coli with fluorescent labelled-flagella #1
This technique allows the the flagella to be seen as the bacteria swim. Note some flagella leaving the flagellar bundle to initiate tumbling.
Movies made available for download by Dr. Howard C. Berg, PI, Bacterial Motility and Behavior. The Roland Institute at Harvard University.
Movie of motile Pseudomonas from YouTube.
Pseudomonas has a single polar flagellum that can rotate both counterclockwise and clockwise but is not visible under phase contrast microscopy.
For example, Helicobacter pylori (inf), the bacterium that causes most gastric and duodenal ulcers, produces urease, an enzyme that breaks down urea into ammonia and bicarbonate, basic compounds that neutralize the hydrochloric acid in the stomach. In addition, the urease is thought to alter the proteins in the mucus changing it from a solid gel to a thinner fluid that the bacteria are able to swim through by way of their flagella. Using motility and chemotaxis, the bacteria move away from the concentrated acid (a repellent) in the lumen of the stomach towards decreasing acid concentration on the epithelium and in the gastric glands of the stomach. At the same time it also uses chemotaxis to swim towards urea (an attractant) being produced by stomach cells. H. pylori subsequently use adhesins to adhere to the epithelial cells of the mucous membranes and to the cells that line the gastric glands. To further help protect the bacterium from the acid, H. pylori produces an acid-inhibitory protein that blocks acid secretion by surrounding parietal cells (def) in the stomach. Bacterial toxins then lead to excessive production of cytokines (def) and chemokines (def), as well as mucinase and phospholipase that damage the gastric mucosa. The cytokines and chemokines, in turn, result in a massive inflammatory response. Neutrophils leave the capillaries, accumulate at the area of infection, and discharge their lysosomes for extracellular killing. This not only kills the bacteria, it also destroys the mucus-secreting mucous membranes of the stomach. H. pylori also secretes toxins such as vacuolating cytotoxin A (VacA) that damages host cells causing them to release nutrients to feed the microcolonies of H. pylori. Without this protective mucus layer, gastric acid causes ulceration of the stomach. This, in turn, leads to either gastritis (def) or gastric and duodenal (def) ulcers. It also uses a type 4 secretion system (T4SS) to inject effector molecules into gastric epithelial cells in order to alter various cellular processes that benefit the bacteria.
Planktonic Pseudomonas aeruginosa uses its polar flagellum to move through water or mucus and make contact with a solid surface such as the body's mucous membranes (See Figs. 1). It then can use pili and cell wall adhesins to attach to the epithelial cells of the mucous membrane. Attachment activates signaling and quorum sensing genes to eventually enable the population of P. aeruginosa to start synthesizing a polysaccharide biofilm composed of alginate. As the biofilm grows, the bacteria lose their flagella to become nonmotile and secrete a variety of enzymes that enable the population to obtain nutrients from the host cells. Eventually the biofilm mushrooms up and develops water channels to deliver water and nutrients to all the bacteria within the biofilm. As the biofilm begins to get too crowded with bacteria, quorum sensing enables some of the Pseudomonas to again produce flagella, escape the biofilm, and colonize a new location.
Because of their thinness, their internal flagella (axial filaments), their corkscrew shape, and their motility (see Fig. 2), spirochetes are more readily able to penetrate host mucous membranes, skin abrasions, etc., and enter the body. Motility and penetration may also enable the spirochetes to penetrate deeper in tissue and enter the lymphatics and bloodstream and disseminate to other body sites. Spirochetes that infect humans include Treponema pallidum (inf), Leptospira (inf), and Borrelia burgdorferi ) (inf).
- Movie of motile Borrelia bergdorferi, the spirochete that causes Lyme disease. From You Tube, courtesy of CytoViva.
- Movie of motile Borrelia bergdorferi, the spirochete that causes Lyme disease.
Along a different line, many bacteria produce enzymes such as elastases and proteases that degrade the extracellular matrix proteins that surround cells and tissues and make it easier for those bacteria to disseminate within the body. For example, Streptococcus pyogenes (inf) produces streptokinase that lyses the fibrin clots (def) produced by the body in order to localize the infection. It also produces DNase that degrades cell-free DNA found in pus and reduces the viscosity of the pus. Both of these enzymes facilitate spread of the bacterium from the localized site to new tissue.
Staphylococcus aureus (inf), on the other hand, produces surface adhesins that bind to extracellular matrix proteins and polysaccharides surrounding host cell tissue, including fibronectin, collagen, laminin, hyaluronic acid, and elastin. S. aureus proteases and hyaluronidase then dissolve these components of the extracellular matrix providing food for the bacteria and enabling the bacteria to spread.
Finally, as will be seen later in this unit under toxins, some bacteria produce toxins that induce diarrhea in the host. Diarrhea is also a part of our innate immunity to flush harmful microbes and toxins out of the intestines. On one hand, diarrhea is an advantage to the body because it flushes out harmful microbes and toxins. On the other hand, it is beneficial for the bacterium inducing the diarrhea because it also flushes out a good deal of the normal flora of the intestines and this reduces the competition for nutrients between normal flora and pathogens. In addition, diarrhea enables the pathogen to more readily leave one host and enter new hosts through the fecal-oral route.
Medscape article on infections associated with organisms mentioned in this Learning Object. Registration to access this website is free.
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.
Last updated: October, 2018
Please send comments and inquiries to Dr. Gary Kaiser