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Microbial invasion can be facilitated by virulence factors, microbial adherence, resistance to antimicrobials, and defects in host defense mechanisms.
Virulence Factors
Virulence factors assist pathogens in invasion and resistance of host defenses; these factors include
Capsule:
Some organisms (eg, certain strains of pneumococci, meningococci, type B Haemophilus influenzae) have a capsule that prevents opsonic antibodies from binding and thus are more virulent than nonencapsulated strains.
Enzymes:
Bacterial proteins with enzymatic activity (eg, protease, hyaluronidase, neuraminidase, elastase, collagenase) facilitate local tissue spread. Invasive organisms (eg, Shigella flexneri, Yersinia enterocolitica) can penetrate and traverse intact eukaryotic cells, facilitating entry from mucosal surfaces.
Some bacteria (eg, Neisseria gonorrhoeae, H. influenzae, Proteus mirabilis, clostridial species, Streptococcus pneumoniae) produce IgA-specific proteases that cleave and inactivate secretory IgA on mucosal surfaces.
Toxins:
Organisms may release toxins (called exotoxins), which are protein molecules that may cause the disease (eg, diphtheria, cholera, tetanus, botulism) or increase the severity of the disease. Most toxins bind to specific target cell receptors. With the exception of preformed toxins responsible for food-borne illnesses, toxins are produced by organisms during the course of infection.
Endotoxin is a lipopolysaccharide produced by gram-negative bacteria and is part of the cell wall. Endotoxin triggers humoral enzymatic mechanisms involving the complement, clotting, fibrinolytic, and kinin pathways and causes much of the morbidity in gram-negative sepsis.
Other factors:
Many microorganisms have mechanisms that impair antibody production by inducing suppressor cells, blocking antigen processing, and inhibiting lymphocyte mitogenesis.
Resistance to the lytic effects of serum complement confers virulence. Among species of N. gonorrhoeae, resistance predisposes to disseminated rather than localized infection.
Some organisms resist the oxidative steps in phagocytosis. For example, Legionella and Listeria either do not elicit or actively suppress the oxidative step, whereas other organisms produce enzymes (eg, catalase, glutathione reductase, superoxide dismutase) that mitigate the oxidative products.
Microbial Adherence
Adherence to surfaces helps microorganisms establish a base from which to penetrate tissues. Among the factors that determine adherence are adhesins (microbial molecules that mediate attachment to a cell) and host receptors to which the adhesins bind. Host receptors include cell surface sugar residues and cell surface proteins (eg, fibronectin) that enhance binding of certain gram-positive organisms (eg, staphylococci). Other determinants of adherence include fine structures on certain bacterial cells (eg, streptococci) called fibrillae, by which some bacteria bind to human epithelial cells. Other bacteria, such as Enterobacteriaceae (eg, Escherichia coli), have specific adhesive organelles called fimbriae or pili. Fimbriae enable the organism to attach to almost all human cells, including neutrophils and epithelial cells in the GU tract, mouth, and intestine.
Biofilm:
Biofilm is a slime layer that can form around certain bacteria and confer resistance to phagocytosis and antibiotics. It develops around Pseudomonas aeruginosa in the lungs of patients with cystic fibrosis and around coagulase-negative staphylococci on synthetic medical devices, such as IV catheters, prosthetic vascular grafts, and suture material. Factors that affect the likelihood of biofilm developing on such medical devices include the material's roughness, chemical composition, and hydrophobicity.
Antimicrobial Resistance
Genetic variability among microbes is inevitable. Use of antimicrobial drugs eventually selects for survival of strains that are capable of resisting them.
In many cases, resistant bacterial strains have acquired genes that are encoded on plasmids or transposons and that enable the microorganisms to synthesize enzymes that
Minimizing inappropriate use of antibiotics is important for public health. Resistance among bacteria is discussed in Bacteria and Antibacterial Drugs: Antibiotic Resistance.
Defects in Host Defense Mechanisms
Two types of immune deficiency states affect the host's ability to fight infection: Primary immune deficiency and secondary (acquired) immune deficiency.
Primary immune deficiencies are genetic in origin; > 100 primary immune deficiency states have been described. Most primary immune deficiencies are recognized during infancy; however, up to 40% are recognized during adolescence or adulthood.
Acquired immune deficiencies are caused by another disease (eg, cancer, HIV infection, chronic disease) or by exposure to a chemical or drug that is toxic to the immune system.
Mechanisms:
Defects in immune responses may involve
Cellular deficiencies are typically T-cell or combined immune defects. T cells contribute to the killing of intracellular organisms; thus, patients with T-cell defects can present with opportunistic infections such as Pneumocystis jirovecii or cryptococcal infections. Chronicity of these infections can lead to failure to thrive, chronic diarrhea, and persistent oral candidiasis.
Humoral deficiencies are typically caused by the failure of B cells to make functioning immunoglobulins. Patients with this type of defect usually have infections involving encapsulated organisms (eg, H. influenzae, streptococci). Patients can present with poor growth, diarrhea, and recurrent sinopulmonary infections.
A defect in the phagocytic system affects the immediate immune response to bacterial infection and can result in development of recurrent abscesses, severe pneumonias, or delayed umbilical cord separation.
Primary complement system defects are particularly rare. Patients with this type of defect may present with recurrent infections with pyogenic bacteria (eg, encapsulated bacteria, Neisseria sp) and have an increased risk of autoimmune disorders (eg, SLE).
Last full review/revision October 2012 by Allan R. Tunkel, MD, PhD
Content last modified November 2012
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