Bacterial damage to host tissues depends on the ability of the bacteria to adhere to host cells, invade cells and tissues, or deliver toxins. Pathogenic bacteria have virulence genes that are frequently found grouped together in clusters called pathogenicity islands. A small number of virulence genes can determine whether a bacterium is harmful. The Salmonella strains that infect humans are so closely related that they are a single species, but only a few virulence genes determine whether an isolate of Salmonella causes life-threatening typhoid fever or self-limited gastroenteritis.
Plasmids (small independently replicating circular DNAs) and bacteriophages (viruses) are genetic elements that spread between bacteria and can carry virulence factors, including toxins or enzymes that confer antibiotic resistance. Exchange of these elements between bacteria can endow the recipient bacteria with a survival advantage and/or the capacity to cause disease. Plasmids or transposons encoding antibiotic resistance can convert an antibiotic-susceptible bacterium into a resistant one, making effective therapy difficult. Carbapenemase genes carried on plasmids have spread among gram-negative bacilli worldwide, resulting in strains for which there are no available effective antibiotics, causing the CDC to list these organisms as an urgent threat.
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Populations of bacteria also can act together in ways that alter their virulence.
Quorum sensing. Many species of bacteria coordinately regulate gene expression within a large population in which specific genes, such as virulence genes, are expressed after bacteria reach high concentrations. This in turn may allow bacteria growing in discrete host sites, such as an abscess or consolidated pneumonia, to overcome host defenses. S. aureus coordinately regulates virulence factors by secreting autoinducer peptides. As the bacteria grow to increasing concentrations, the level of the autoinducer peptide increases, stimulating exotoxin production.
Biofilms. Communities of bacteria can live within a viscous layer of extracellular polysaccharides that adhere to host tissues or devices such as intravascular catheters and artificial joints. Biofilms make bacteria inaccessible to immune effector mechanisms and increase their resistance to anti-microbial drugs. Biofilm formation seems to be important in the persistence and relapse of infections such as bacterial endocarditis, artificial joint infections, and respiratory infections in individuals with cystic fibrosis.
Bacterial Adherence to Host Cells
Bacterial surface molecules that bind to host cells or extracellular matrix are called adhesins. Diverse surface structures are involved in adhesion of various bacteria (see
Fig.
9.2 ). S. pyogenes has protein F and teichoic acid projecting from its cell wall that bind to fibronectin on the surface of host cells and in the extracellular matrix. Other bacteria have filamentous proteins called pili on their surfaces. Stalks of pili are structurally conserved, whereas amino acids on the tips of the pili vary and determine the binding specificity of the bacteria. Strains of E. coli that cause urinary tract infections uniquely express a specific P pilus that binds to a Gal(α1–4)Gal moiety expressed on uroepithelial cells. Pili on N. gonorrhoeae bacteria mediate adherence of the bacteria to host cells and also are targets of the host antibody response. Antigenic variation affecting the antigens expressed in the pili is an important mechanism by which N. gonorrhoeae escapes the immune response.
Any bacterial substance that contributes to illness can be considered a toxin. Toxins are subclassified as endotoxins, which are components of the bacterial cell, or exotoxins, which are proteins that are secreted by the bacterium.
Bacterial endotoxin is a lipopolysaccharide (LPS) that is a component of the outer membrane of gram-negative bacteria (see