I. BACTERIAL PATHOGENESIS
B. VIRULENCE FACTORS THAT PROMOTE BACTERIAL COLONIZATION OF THE HOST
2. The ability to adhere to host cells and resist physical removal
The overall purpose of this Learning Object is:
1) to learn how the ability to adhere to host cells and resist physical removal plays a role in bacterial pathogenicity by promoting colonization;
2) to learn three different ways bacteria may adhere to host cells and resist physical removal; and
3) to introduce several examples of medically important bacteria that use each of these mechanisms in order to adhere to and colonize host cells.
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.
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 that enable bacteria to adhere to host cells and resist physical removal.
Virulence Factors that Promote Bacterial Colonization of the Host
2. The Ability to Adhere to Host Cells and Resist Physical Removal
As we will see in Unit 4, one of the body's innate defenses is the ability to physically remove bacteria from the body through such means as the constant shedding of surface epithelial cells from the skin and mucous membranes, the removal of bacteria by such means as coughing, sneezing, vomiting, and diarrhea, and bacterial removal by bodily fluids such as saliva, blood, mucous, and urine. Bacteria may resist this physical removal by producing pili, cell wall adhesin proteins, and/or biofilm-producing capsules. In addition, the physical attachment of bacteria to host cells can also serve as a signal for the activation of genes involved in bacterial virulence. This process is known as signal transduction.
1. Using Pili (fimbriae) to Adhere to Host Cells (def)
As seen in Unit 1, pili enable some organisms to adhere to receptors on target host cells (see Fig. 1) and thus colonize and resist flushing by the body. Pili are thin, protein tubes originating from the cytoplasmic membrane and are found in virtually all gram-negative bacteria but not in many gram-positive bacteria. The pilus has a shaft composed of a protein called pilin. At the end of the shaft is the adhesive tip structure having a shape corresponding to that of specific glycoprotein or glycolipid receptors on a host cell (see Fig. 2). Because both the bacteria and the host cells have a negative charge, pili may enable the bacteria to bind to host cells without initially having to get close enough to be pushed away by electrostatic repulsion. Once attached to the host cell, the pili can depolymerize and enable adhesions in the bacterial cell wall to make more intamate contact.
You Tube animation showing Pseudomonas using motility, pili, and exotoxins to cause an infection. 3D Mecical Animations Library and Downloads, www.rufusrajadurai. wetpaint.comBacteria are constantly losing and reforming pili as they grow in the body and the same bacterium may switch the adhesive tips of the pili in order to adhere to different types of cells and evade immune defenses (see Fig. 3).
For example:
- To cause infection, Neisseria gonorrhoeae (inf) must first colonize a mucosal surface composed of columnar epithelial cells. Pili alow for this initial binding and, in fact, N. gonorrhoeae is able to rapidly lose pili and synthesize new ones with a different adhesive tip, enabling the bacterium to adhere to a variety of tissues and cells including sperm, the epithelial cells of the mucous membranes lining the throat, genitourinary tract, rectum, and the conjunctiva of the eye. Subsequently, the bacterium is able to make more intimate contact with the host cell surface by way of a cell wall adhesin called Opa (see below).
- The pili of Neisseria meningitidis (inf) allow it to adhere to mucosal epithelial cells in the nasopharynx where it is often asymptomatic. From there, however, it sometimes enters the blood and meninges and causes septicemia and meningitis.
Highlighted Bacterium: Neisseria meningitidisClick on this link, read the description of Neisseria meningitidis, and be able to match the bacterium with its description on an exam.
- Uropathogenic strains of Escherichia coli (def) can produce pili that enable the bacterium to adhere to the urinary epithelium and cause urinary tract infections. They also produce afimbrial adhesins (see below) for attachment to epithelial cells. Enteropathogenic E.coli use pili to adhere to intestinal mucosal cells.
- To view an electron micrograph E. coli with pili, see Dennis Kunkel's Microscopy at the University of Hawaii-Manoa.
- To view electron micrographs of enteropathogenic E. coli (EPEC) adhering to intestinal cells, see Donnenberg Lab Images at the University of Maryland Medical School.
- Pili of Vibrio cholerae (inf) allow it to adhere to cells of the intestinal mucosa and resist the flushing action of diarrhea.
- Pili of Pseudomonas aeruginosa (inf) allow it to initially colonize wounds or the lung.
2. Using Adhesins to Adhere to Host Cells(def)
Adhesins are surface proteins found in the cell wall of various bacteria that bind to specific receptor molecules on the surface of host cells and enable the bacterium to adhere intimately to that cell in order to colonize and resist physical removal (see Fig. 5). Many, if not most bacteria probably use one or more adhesins to colonize host cells.
For example:
- Streptococcus pyogenes (see electron micrograph) (group A beta streptococci) (inf) produce a number of adhesins:
- Protein F that binds to fibronectin (def), a common protein on epithelial cells. In this way it is able to adhere to the lymphatics and mucous membranes of the upper respiratory tract and cause streptococcal pharyngitis (strep throat).
- Lipoteichoic acid binds to fibronectin on epithelial cells.
- M-protein also functions as an adhesin.
- The tip of the spirochete Treponema pallidum (inf) contains adhesins that are able to bind to fibronectin (def) on epithelial cells.
Scanning electron Micrograph of T. pallidum adhering to a host cell by its tip.
- The tip of the spirochete Borrelia burgdorferi (inf) contains adhesins that can bind to various host cells.
- Bordetella pertussis (inf) produces several adhesins (see Fig. 4):
- Filamentous hemagglutinin is an adhesin that allows the bacterium to adhere to galactose residues of the glycolipids on the membrane of ciliated epithelial cells of the respiratory tract.
- Pertussis toxin also functions as an adhesin. One subunit of the pertussis toxin remains bound to the bacterial cell wall while another subunit binds to the glycolipids on the membrane of ciliated epithelial cells of the respiratory tract.
- B. Pertussis also produces an adhesin called pertactin that further enables the bacterium to adhere to cells.
- Neisseria gonorrhoeae (inf) produces an adhesin called Opa (protein II) that enables the bacterium to make a more intimate contact with the host cell after it first adheres with its pili. Like with adhesive tips of pili, N. gonorrhoeae has multiple alleles for Opa protein adhesins enabling the bacterium to adhere to a variety of host cell types.
- Salmonella (inf) uses adhesins to attach to the microvilli of intestinal epithelial cells as well as M-cells. It subsequently enters M-cells by way of invasins (see below).
- Pseudomonas aeruginosa (inf) binds to the mucin layer that lines the airways by means of an adhesin.
- Helicobacter pylori (inf) is able to bind to carbohydrate residues on gastrointestinal epithelial cells and the Lewis b antigen on the gastrointestinal epithelial cells and red blood cells of individuals with type O blood. See ulcers in the Bugs in the News web page of the University of Kansas.
- Streptococcus pneumoniae (inf) assembles a variety of choline-binding proteins that attach both to the surface of the bacterium and to choline molecules on nasopharyngeal, lung, and endothelial cells. These choline-binding proteins allow the pneumococcus to colonize the upper and lower respiratory tract, and also appear to be essential in the bacterium traversing from the blood to the cerebrospinal fluid.
- Staphylococcus aureus uses protein A as an adhesin to adhere to various host cells. It also helps the bacterium to resist phagocytosis.
3. Using Capsules (biofilms) to Adhere to Host Cells
Many normal flora bacteria produce a capsular polysaccharide matrix or glycocalyx to form a biofilm (def) on host tissue (see Fig. 5). A biofilm(def) consists of layers of bacterial populations adhering to host cells and embedded in a common capsular mass. For example:
- Streptococcus mutans, a bacterium responsible for initiating dental caries, breaks down sucrose into glucose and fructose. It uses an enzyme called glucosyltransferase to convert the glucose to a sticky polysaccharide called dextran that forms its glycocalyx and allows the S. mutans to adhere to the enamel of the tooth. This dextran mesh traps the S. mutans, along with other bacteria and debris, and forms plaque. S. mutans also ferments glucose in order to produce energy. The fermentation of glucose results in the production of lactic acid that is released onto the surface of the tooth and initiates decay.
- Scanning electron micrograph of Streptococcus growing in the enamel of a tooth.© Lloyd Simonson, author. Licensed for use, ASM MicrobeLibrary.
- Scanning electron micrograph of dental plaque.© H. Busscher, H. van der Mei, W. Jongebloed, R Bos, authors. Licensed for use, ASM MicrobeLibrary.
Many pathogenic bacteria, as well as normal flora, form complex bacterial communities as biofilms. Bacteria in biofilms are often able to communicate with one another by a process called quorum sensing (discussed later in this unit) and are able to interact with and adapt to their environment as a population of bacteria rather than as individual bacteria. By living as a community of bacteria as a biofilm, these bacteria are:
1. better able to resist attack by antibiotics, and
2. are better able to resist the host immune system.
For example, most children suffering from chronic ear infection (otitis media) have a biofilm of bacteria in their middle ear. This biofilm contains bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis and enables the bacteria to chronically colonize the middle ear as well as resist body defenses and antibiotics.
- Scanning electron micrograph of Listeria growing on a stainless steel surface. © Amy Lee Wong, author. Licensed for use, ASM MicrobeLibrary.
- Scanning electron micrograph of Pseudomonas growing on bronchial mucosa. © Hiroyuki Kobayashi, author. Licensed for use, ASM MicrobeLibrary.
- Scanning electron micrograph of Staphylococcus aureus forming a biofilm in an indwelling catheter courtesy of CDC.
For further information on bacterial pathogenesis, see the online Microbiology Web Textbook at the University of Wisconsin-Madison.
E-Medicine article on infections associated with organisms mentioned in this Learning Object. Registration to access this website is free.
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