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Factors Facilitating Microbial Invasion

By

Larry M. Bush

, MD, FACP, Charles E. Schmidt College of Medicine, Florida Atlantic University

Last full review/revision Jul 2020| Content last modified Jul 2020
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Microbial invasion can be facilitated by the following:

  • Virulence factors

  • Microbial adherence

  • Resistance to antimicrobials

  • Defects in host defense mechanisms

Virulence Factors

Virulence factors assist pathogens in invasion and resistance of host defenses; these factors include

  • Capsule

  • Enzymes

  • Toxins

Capsule

Some organisms (eg, certain strains of pneumococci, meningococci, Haemophilus influenzae type b Haemophilus Infections The gram-negative bacteria Haemophilus species cause numerous mild and serious infections, including bacteremia, meningitis, pneumonia, sinusitis, otitis media, cellulitis, and epiglottitis... read more ) have a capsule that blocks phagocytosis, making these organisms more virulent than nonencapsulated strains. However, capsule-specific opsonic antibodies can bind to the bacterial capsule and facilitate phagocytosis.

Enzymes

Toxins

Organisms may release toxins (called exotoxins), which are protein molecules that may cause disease (eg, diphtheria Diphtheria Diphtheria is an acute pharyngeal or cutaneous infection caused mainly by toxigenic strains of the gram-positive bacillusCorynebacterium diphtheriae and rarely by other, less common Corynebacterium... read more Diphtheria , cholera Cholera Cholera is an acute infection of the small bowel by the gram-negative bacterium Vibrio cholerae, which secretes a toxin that causes copious watery diarrhea, leading to dehydration, oliguria... read more , tetanus Tetanus Tetanus is acute poisoning from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for the name lockjaw... read more Tetanus , botulism Botulism Botulism is poisoning that is due to Clostridium botulinum toxin and that affects the peripheral nerves. Botulism may occur without infection if toxin is ingested, injected, or inhaled. Symptoms... read more ) or increase the severity of the disease. Most toxins bind to specific target cell receptors. With the exception of preformed toxins responsible for some food-borne illnesses (eg, botulism Botulism Botulism is poisoning that is due to Clostridium botulinum toxin and that affects the peripheral nerves. Botulism may occur without infection if toxin is ingested, injected, or inhaled. Symptoms... read more , staphylococcal or Bacillus cereus food poisoning), 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 bacterial sepsis.

Other factors

Some microorganisms are more virulent because they do the following:

  • Impair antibody production

  • Resist the lytic effects of serum complement

  • Resist the oxidative steps in phagocytosis

  • Produce superantigens

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 viruses and bacteria produce superantigens that bypass the immune system, cause nonspecific activation of inordinate numbers of naive T cells, and thus cause excessive and potentially destructive inflammation mediated by massive release of proinflammatory cytokines.

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 Staphylococcal Infections Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more Staphylococcal Infections ).

Other determinants of adherence include fine structures on certain bacterial cells (eg, streptococci Streptococcal Infections Streptococci are gram-positive aerobic organisms that cause many disorders, including pharyngitis, pneumonia, wound and skin infections, sepsis, and endocarditis. Symptoms vary with the organ... read more Streptococcal Infections ) called fibrillae, by which some bacteria bind to human epithelial cells. Other bacteria, such as Enterobacteriaceae (eg, Escherichia coli Escherichia coli Infections The gram-negative bacterium Escherichia coli is the most numerous aerobic commensal inhabitant of the large intestine. Certain strains cause diarrhea, and all can cause infection when they invade... read more ), 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 genitourinary tract, mouth, and intestine.

Biofilm

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.

Emergence of antimicrobial resistance may be due to spontaneous mutation of chromosomal genes. In many cases, resistant bacterial strains have acquired mobile genetic elements from other microorganisms. These elements are encoded on plasmids or transposons and enable the microorganisms to synthesize enzymes that

  • Modify or inactivate the antimicrobial agent

  • Change the bacterial cell’s ability to accumulate the antimicrobial agent

  • Resist inhibition by the antimicrobial agent

Minimizing inappropriate use of antibiotics in humans and in animal farming is important for public health.

Defects in Host Defense Mechanisms

Two types of immune deficiency states affect the host’s ability to fight infection:

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 first 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

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