Chapter Summary


  • Infection with a microbe does not always lead to disease.
  • Primary pathogens have mechanisms that help the organism circumvent host defenses.
  • Opportunistic pathogens cause disease only in a compromised host.
  • Pathogenicity refers to the mechanisms a pathogen uses to produce disease and how efficient the organism is at causing disease, whereas virulence is a measure of disease severity.
  • Diseases can be spread by direct or indirect contact between infected and uninfected persons/animals or by insect vectors.
  • Pathogens use portals of entry best suited to their mechanisms of pathogenesis.
  • Immunopathogenesis occurs when the immune system’s response to an infection damages host cells and tissues.


  • Pathogenicity islands are DNA sequences within a species that are acquired by horizontal gene transfer from a different species.
  • Virulence genes encode genes whose products enhance the disease-causing ability of the organism. Many virulence genes can be found within pathogenicity islands, but some are located outside of an obvious genomic island or reside in plasmids.
  • Pathogenicity islands contain distinct features, such as GC content and the remnants of phages or plasmids, that mark them as being different from the rest of the genome.
  • Gene transfer mechanisms will, by horizontal transfer, move virulence factor genes and pathogenicity islands among bacterial strains and species.


  • Bacteria use pili and nonpilus adhesins to attach to host cells.
  • Type I pili produce a static attachment to the host cell, whereas type IV pili continually assemble and disassemble.
  • Nonpilus adhesins are bacterial surface proteins, or other molecules, that can tighten interactions between bacteria and target cells.
  • Biofilms play an important role in chronic infections by enabling persistent adherence and resistance to bacterial host defenses and antimicrobial agents.


  • There are five categories of protein exotoxins based on mode of action. These include toxins that disrupt membranes, inhibit protein synthesis, or alter host cell signal molecule synthesis, as well as superantigens and target- specific proteases.
  • AB-subunit toxins are common. The B subunit promotes penetration through host cell membranes, and the A subunit has toxic activity.
  • Staphylococcus aureus alpha toxin forms pores in host cell membranes.
  • Cholera toxin, E. coli labile toxin, and pertussis toxin are AB toxins that alter host cAMP production by adding ADP-ribose groups to different G-factor proteins.
  • Shiga toxin is an AB toxin that cleaves host cell 28S rRNA in host cell ribosomes.
  • Anthrax toxin is a three-part AB toxin with one B subunit (protective antigen) and two different A subunits that affect cAMP levels (edema factor) and cleave host protein kinases (lethal factor).
  • Lipopolysaccharide (LPS), known as endotoxin, is an integral component of Gram-negative outer membranes and an important virulence factor that triggers massive release of cytokines from host cells. The indiscriminate release of cytokines can trigger fever, shock, and death.


  • Many pathogens use specific protein secretion pathways to deliver toxins.
  • Type II secretion systems use a pilus-like extraction/ retraction mechanism to push proteins out of the cell.
  • Type III secretion uses a molecular syringe to inject proteins from the bacterial cytoplasm into the host cytoplasm.
  • Type IV secretion utilizes an entourage of proteins that resemble conjugation machinery to secrete proteins from either the cytoplasm or the periplasm.


  • In vivo expression technology (IVET) is a positive selection tool to identify genes required for a pathogen to grow in vivo.
  • Signature-tagged mutagenesis uses negative selection to identify genes required for in vivo growth.
  • Genomic tools were used to predict mechanisms of Helicobacter pylori pathogenesis and the growth requirements for the Whipple’s disease microbe.


  • Intracellular bacterial pathogens attempt to avoid the immune system by growing inside host cells. They use different mechanisms to avoid intracellular death.
  • Hemolysins are used by certain pathogens to escape from the phagosome and grow in the host cytoplasm.
  • Actin tails are used by some microbes to move within and between host cells.
  • Inhibiting phagosome-lysosome fusion is one way pathogens can survive in phagosomes.
  • Specialized physiologies enable some organisms to survive in the normally hostile environment of fused phagolysosomes.
  • Extracellularly, pathogens evade the immune system by hiding in capsules, by changing their surface proteins, by triggering apoptosis, or by using molecular mimicry.
  • Two-component signal transduction systems can regulate virulence gene expression in response to the environment.
  • Quorum sensing may prevent pathogens from releasing toxic compounds too early during infection.


  • Multiple reinfection of the same person by a virus can occur because different strains of the virus have minor sequence differences in attachment proteins (for example, capsid). Because of these differences, neutralizing antibodies made during a previous infection are ineffective against the new strain.
  • Viral infection can increase a patient’s susceptibility to other, less virulent microbes.
  • Antigenic shifts in a viral antigen (as in the hemagglutinin of influenza) can lead to a new pandemic of the disease.
  • Animals coinfected with two viruses can serve as incubators for antigenic shifts or the evolution of new viruses.
  • Binding to host cells can involve a single host receptor (as in rhinovirus) or multiple receptors (as in HIV).
  • Virus-infected cells can secrete proteins that enter uninfected cells and disrupt signaling pathways.