Microbiology Chapter on Pathogens and Hosts

Microbial Pathogenesis Overview

• Host-pathogen interactions are studied, including how microbes attach to host cells, how toxins affect host functions, and how toxins and effectors are deployed.

Introduction

• Mammalian defenses include physical, chemical, and immunological barriers against disease-causing microbes.
• Pathogenic microbes exploit weaknesses in defenses to cause disease.
• How can a microorganism too small to be seen kill a human a million times larger? This fundamental question is explored in the study of host-pathogen interactions.

Host-Pathogen Interactions

• Humans and their ancestors have experienced infections for millions of years.
• Robert Koch discovered Bacillus anthracis causes anthrax.

The Language of Pathogenesis

• Parasites benefit at the host's expense; they include bacteria, viruses, fungi, and protozoa.
• Ectoparasites live on the host's surface, while endoparasites live inside the body.
• Infection occurs when a pathogen or parasite grows in/on a host. Not all infections cause disease.
• Primary pathogens cause disease in healthy hosts, opportunistic pathogens cause disease in compromised hosts, and latent infections involve microbes entering a dormant state.

Infection Cycles

• The cycle describes the transmission route of the infectious organism.
• Horizontal transmission involves direct (e.g., sneezing, touch) and indirect (e.g., fomites, food, water) contact.
• Vertical transmission occurs from mother to fetus during pregnancy or birth.
• Vector transmission involves arthropods carrying pathogens (e.g., mosquitoes).

Reservoirs and Portals of Entry

• Reservoirs are environments or animals harboring pathogens (e.g., monkeys for yellow fever, birds for eastern equine encephalitis virus).
• Asymptomatic carriers are individuals who harbor pathogens but show no symptoms.

Immunopathogenesis

• Immunopathogenesis is the immune response to a pathogen that causes tissue/organ damage.
• Study of both pathogenic mechanisms and immunopathogenesis symptoms are crucial.

Effect of Infections on the Microbiome

• Host's normal microbiome is affected by pathogen growth and immune response.
• Example: Diarrhea reduces gut microbiota; intestinal pathogens alter nutrient availability.

Virulence Factors

• Requirements for disease include entering the host, finding a niche, avoiding host defenses, multiplying, and transmitting to a new host.
• Virulence factors (e.g., toxins, attachment proteins, capsules) are encoded by virulence genes.
• Molecular Koch's postulates describe determining pathogenic strains by inactivation of a pathogen gene and reversion allowing restoration to pathogenicity.

Pathogenicity Islands

• Clusters of pathogenicity genes encoding virulence functions.
• These genes can be transmitted horizontally via conjugation or transduction.
• Unique GC/AT ratio, linkage to tRNA genes, association with phages/plasmids may be seen as anomalies.

Microbial Attachment

• Attachment/adhesion is the initial step toward infection.
• Adhesins are microbial factors that promote attachment (e.g., pili, adherence proteins, cell surface molecules).

Pili (Fimbriae)

• Hair-like appendages made of pilin protein subunits.
• Tips contain receptors (e.g., FimH) for attaching to host cell receptors.
• Types of pili include Type I (static attachment) and Type IV (dynamic attachment via assembly/disassembly).

Assembly of Type I Pili

• Protein subunits assemble like jigsaw pieces.
• New subunits are added to the bottom of the structure.

Type IV Pili - Model of Pilus Assembly and Disassembly

• At least a dozen proteins are involved.
• Functions include pili elongation for attachment, retraction for cell movement, and disassembly.
• Examples include E. coli and N. meningitidis.

Nonpilus Adhesins

• These adhesins strengthen interactions between bacteria and target cells.
• Examples include Streptococcus pyogenes M protein binding to host cell fibronectin.

Susceptibility to Infections

• Factors include immunocompetence (the ability to resist pathogens) and receptor availability.

Host Receptors and Pathogen Susceptibility

• Pathogens use specific surface structures (receptors) to recognize and attach to host cells.
• Variations in receptors between individuals can affect susceptibility.

Toxins Subvert Host Functions

• Exotoxins are proteins produced and secreted by various bacteria.
• Exotoxins kill host cells and utilize their nutrients.
• Endotoxins are part of Gram-negative bacterial lipopolysaccharide (LPS) and hyper-activate the immune system.

Producing Organisms & Exotoxins (Chemical, Denatured, Mode of Action, Enzyme Activity, Toxicity, Immunogenicity, Vaccine, Fever Production)

• A table shows categories of microbial exotoxins with their chemical properties (protein or LPS),denaturation status, specific actions, and their impact (high or low) on various aspects including enzyme activity and fever production.

Two-Subunit AB Exotoxins (Structure, A Subunit, B Subunit, ADP-Ribosyltransferase Enzymes)

• These toxins have an A subunit for toxicity and a B subunit for binding host cells and delivering the A subunit.
• AB5 toxins contain 5 identical B subunits and 1 A subunit.
• ADP ribosyltransferase enzymes modify protein structure and function. This relates specifically to the way some toxins function, that is transferring ADP-ribose groups.

Examples: Cholera Toxin, Anthrax Toxin

• Cholera toxin increases cAMP levels in host cells, leading to diarrhea.
• Anthrax toxin has subunits with functions causing cytotoxicity involving proteins (e.g., edema factor and lethal factor)
• Shiga toxin interferes with protein synthesis.

Deployment of Toxins and Effectors (Protein secretory proteins, Type II, III, IV, Mechanism, Examples)

• Bacteria use protein secretory systems to move toxins into host cells
• Type III secretory system (T3SS) injects proteins into host cells. The T3SS, in this example, contains a tiny molecular syringe and allows for the transfer of proteins to aid in the infection.

Surviving Within the Host (Extracellular Immune Avoidance)

• Strategies for survival include capsule production, inhibiting antibody binding, inducing apoptosis, or altering surface antigens.
• Intracellular immune avoidance involves strategies to avoid phagosome-lysosome fusion, growing inside the phagolysosome, or escaping the phagosome, relying on autophagy.
• Pathogens employ molecular tricks to misdirect immune responses, buy time to overwhelm the host, or use autophagy, an internal cellular process.

Immune Avoidance (Two-Subunit AB toxins, Endotoxin, Protein Secretion Pathways, Bacteria, examples, mechanisms)

• Bacteria employ molecular mimicry, interfering with autophagy, and redirecting ubiquitylation signals (all methods of evading the host immune responses).

Test your understanding of key concepts in microbiology, focusing on pathogens, host interactions, and factors influencing infections. This quiz covers various aspects including Type IV pili, virulence, and opportunistic pathogens. Perfect for students looking to deepen their knowledge in microbial pathogenesis.