Establishment of a bacterial infection in a host presupposes the capacity of the invaders to overcome the host's nonspecific immune defenses. The most important mechanisms used by pathogenic bacteria are:
— Capsule. Renders phagocytosis more difficult. Capsule components may block alternative activation of complement so that C3b is lacking (ligand for C3b receptor of phagocytes) on the surface of encapsulated bacteria. Microorganisms that use this strategy include Streptococcus pneumoniae and Haemophilus influenzae.
— Phagocyte toxins. Examples: leukocidin from staphylococci, streptolysin from streptococci.
— Macrophages may be disabled by the type III secretion system (see p. 17) of certain Gram-negative bacteria (for example salmonellae, shigellae, yersiniae, and coli bacteria). This system is used to inject toxic proteins into the macrophages.
— Inhibition ofphagosome-lysosomefusion. Examples: tuberculosis bacteria, gonococci, Chlamydia psittaci.
— Inhibition of the phagocytic "oxidative burst." No formation of reactive O2 radicals in phagocytes. Examples: Legionella pneumophilia, Salmonella ty-phi.
■ Serum resistance. Resistance of Gram-negative bacteria to complement. A lipopolysaccharide in the outer membrane is modified in such a way that it cannot initiate alternative activation of the complement system. As a result, the membrane attack complex (C5b6789), which would otherwise lyse holes in the outer membrane, is no longer produced (see p. 86ff.).
■ Siderophores. Siderophores (e.g., enterochelin, aerobactin) are low-molecular-weight iron-binding molecules that transport Fe3+ actively into the intracellular space. They complex with iron, thereby stealing this element from proteins containing iron (transferrin, lactoferrin). The intricate iron transport system is localized in the cytoplasmic membrane, and in Gramnegative bacteria in the outer membrane as well. To thrive, bacteria require 10-5 mol/l free iron ions. The free availability of only about 10-20 mol/l iron in human body fluids thus presents a challenge to them.
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