Bacteria and Bacterial Infection (World of Microbiology and Immunology)
Infectious diseases depend on the interplay between the ability of pathogens to invade and/or proliferate in the body and the degree to which the body is able to resist. If the ability of a microorganism to invade, proliferate, and cause damage in the body exceeds the body's protective capacities, a disease state occurs. Infection refers to the growth of microorganisms in the body of a host. Infection is not synonymous with disease because infection does not always lead to injury, even if the pathogen is potentially virulent (able to cause disease). In a disease state, the host is harmed in some way, whereas infection refers to any situation in which a microorganism is established and growing in a host, whether or not the host is harmed.
The steps of pathogenesis, the progression of a disease state, include entry, colonization, and growth. Pathogens like bacteria use several strategies to establish virulence. The bacteria must usually gain access to host tissues and multiply before damage can be done. In most cases this requires the penetration of the skin, mucous membranes, or intestinal epithelium, surfaces that normally act as microbial barriers. Passage through the skin into subcutaneous layers almost always occurs through wounds and in rare instances pathogens penetrate through unbroken skin.
Most infections begin with the adherence of bacteria to specific cells on the mucous membranes of the respiratory, alimentary, or genitourinary tract. Many bacteria possess surface macromolecules that bind to complementary acceptor molecules on the surfaces of certain animal cells, thus promoting specific and firm adherence. Certain of these macromolecules are polysaccharides and form a meshwork of fibers called the glycocalyx. This can be important for fixing bacteria to host cells. Other proteins are specific, e.g., M-proteins on the surface of Streptococcus pyogenes which facilitate binding to the respiratory mucosal receptor. Also structures known as fimbrae may be important in the attachment process. For example, the fimbrae of Neiseria gonorrhoeae play a key role in the attachment of this organism to the urogenital epithelium where it causes a sexually transmitted disease. Also, it has been shown that fimbriated strains of Escherichia coli are much more frequent causes of urinary tract infections than strains lacking fimbrae, showing that these structures can indeed promote the capacity of bacteria to cause infection.
The next stage of infection is invasion that is the penetration of the epithelium to generate pathogenicity. At the point of entry, usually at small breaks or lesions in the skin or mucosal surfaces, growth is often established in the submucosa. Growth can also be established on intact mucosal surfaces, especially if the normal flora is altered or eliminated. Pathogen growth may also be established at sites distant from the original point of entry. Access to distant, usually interior, sites occurs through the blood or lymphatic system.
If a pathogen gains access to tissues by adhesion and invasion, it must then multiply, a process called colonization. Colonization requires that the pathogen bind to specific tissue surface receptors and overcome any non-specific or immune host defenses. The initial inoculum is rarely sufficient to cause damage. A pathogen must grow within host tissues in order to produce disease. If a pathogen is to grow, it must find appropriate nutrients and environmental conditions in the host. Temperature, pH and reduction potential are environmental factors that affect pathogen growth, but the availability of microbial nutrients in host tissues is most important. Not all nutrients may be plentiful in different regions. Soluble nutrients such as sugars, amino acids and organic acids may often be in short supply and organisms able to utilize complex nutrient sources such as glycogen may be favored. Trace elements may also be in short supply and can influence the establishment of a pathogen. For example, iron is thought to have a strong influence on microbial growth. Specific iron binding proteins called transferrin and lactoferrin exist in human cells and transfer iron through the body. Such is the affinity of these proteins for iron, that microbial iron deficiency may be common and administration of a soluble iron salt may greatly increase the virulence of some pathogens. Many bacteria produce iron-chelating compounds known as siderophores, which help them to obtain iron from the environment. Some iron chelators isolated from pathogenic bacteria are so efficient that they can actually remove iron from host iron binding proteins. For example, a siderophore called aerobactin, produced by certain strains of E. coli and encoded by the Col V plasmid, readily removes iron bound to transferring.
After initial entry, the organism often remains localized and multiplies, producing a small focus of infection such as a boil, carbuncle or pimple. For example, these commonly arise from Staphylococcus infections of the skin. Alternatively, the organism may pass through the lymphatic vessels and be deposited in lymph nodes. If an organism reaches the blood, it will be distributed to distal parts of the body, usually concentrating in the liver or spleen. Spread of the pathogen through the blood and lymph systems can result in generalized (systemic) infection of the body, with the organism growing in a variety of tissues. If extensive bacterial growth in tissues occurs, some of the organisms may be shed into the bloodstream, a condition known as bacteremia.
A number of bacteria produce extracellular proteins, which break down host tissues, encourage the spread of the organism and aid the establishment and maintenance of disease. These proteins, which are mostly enzymes, are called
The ways in which pathogens bring about damage to the host are diverse. Only rarely are symptoms of a disease due simply to the presence of a large number of microorganisms, although a large mass of bacterial cells can block vessels or heart valves or clog the air passages of the lungs. In many cases, pathogenic bacteria produce toxins that are responsible for host damage. Toxins released extracellularly are called exotoxins, and these may travel from the focus of infection to distant parts of the body and cause damage in regions far removed from the site of microbial growth. The first example of an exotoxin to be discovered was the diphtheria toxin produced by Corynebacterium diphtheriae. Some Gram negative bacteria produce lipopolysaccharides as part of their cell walls, which under some conditions can be toxic. These are called endotoxins and have been studied primarily in the genera Escherichia, Shigella, and Salmonella.
See also Anti-adhesion methods; Antibiotic resistance, tests for; Immune system; Immunofluorescence; Immunology; Infection and resistance; Infection control