Disease Triads: Pathogens

Pathogen

a specific causative (infectious) agent of disease

Infection

the establishment of pathogenic agents in or on a suitable host

Disease

alteration in structure or function from normal in human, animal, or plant

Infectivity

• the ability of an agent to cause infection in a susceptible host

• attack rate = infected/exposed

• R₀ how many have been infected after brief exposure

Pathogenicity

• the ability of a microbial agent to induce disease

• illness rate = ill/infected

Virulence

• the severity of disease produced after infection occurs

• case fatality rate = fatal/ill

What are the six types of pathogens?

• helminths

• fungi

• protists

• bacteria

• viruses

• prions

Helminths

• worm-like parasites

  • multicellular eukaryotic invertebrates

  • platyhelminthes (flukes and tapeworms) vs. nematodes (roundworms)

• complex reproductive cycle

  • development includes egg, larval, and adult stages

  • most require at least part of their life cycle outside of the primary host

  • often have intermediate hosts in the lifecycle

• sub-classifications

  • trematodes: flukes

  • cestodes: tapeworms

  • nematodes: roundworms

Fungi

• multi or unicellular eukaryotic organisms

  • have a cell wall composed of mannan, glucan, and chitin

  • several pathogens are dimorphic

    • mold forms in the environment

    • yeast forms in infected tissue

• can undergo sexual or asexual reproduction

  • asexual reproduction via conidia

  • sexual reproduction via spores

• can cause localized or systemic disease

Protists

• unicellular eukaryotes

• protozoa

  • heterotrophic - acquire nutrients from the environment

    • often by pinocytosis or phagocytosis

  • reproduction may be sexual and/or asexual

    • often have complex life cycle

• algae

  • typically autotrophic - have chlorophyll

    • most common pathogenic algae lacks chlorophyll

      • prototheca

Bacteria

• unicellular prokaryotic organisms

• reproduce asexually

• morphology varies both in structure and shape

• gram-positive: have peptidoglycan in their cell walls

• gram-negative: thinner peptidoglycan wall with a separate outer membrane

Viruses

• genetic material contained in a protein coat

  • may be DNA or RNA

• reproduction requires host cell machinery

• viruses may become latent in the host

  • these can be re-activated later

• some viruses may insert into host genome in high-risk areas

  • this can induce cancer in the host

Prions

• transmissible protein agents

  • misfolded form of a normal protein

• causes neurodegenerative disorders

• some cases are spontaneous, others are acquired

• many spcies impacted

  • Bovine spongiform encephalopathy

  • Creutzfeldt-Jakod Disease

  • Variant Creutzfeldt-Jakob Disease

  • Kuru

  • Chronic Wasting Disease

  • Scrapie

  • Transmissible mink encephalopathy

• a chronic, long-term condition that takes a long time for clinical signs to show

How do the pathogens handle survival outside of the host?

• helminths: essential

• protists: thrives

• bacteria: survives

• viruses: die

Virulence defense mechanisms include …

• avoiding mechanical clearance

• escaping host immune response

• evading host nutrient sequestration

• resisting treatment

Virulence offensive mechanisms include

• toxin production

  • endotoxins

  • exotoxins

Avoiding mechanical clearance

• methods of pathogen clearance:

  • cilia

  • mucous

  • flow of contents via GI or urinary tract

• avoided by:

  • adhesins

  • motility

Adhesins

• outer surface molecules that allow adherence to host surfaces

  • fimbriae

  • pili

• characteristics

  • adhere to specific substrates

    • protein-protein or protein-carbohydrate

  • important in primary mucosal infection

    • plays a role in secondary adhesion too

  • highly specific binding

    • species specificity/tissue tropism

Motility

• outer surface structures that allow movement

  • flagella

    • long bacterial appendage

    • allows motility in fluid environments

  • actin-based motility

    • allows bacteria to move within and between host cells

    • seen in Listeria and Shigella

Escaping host immune response

• entry into host cells

  • reduces exposure to immune response

  • easier access to nutrients

  • allows deeper penetration into host

  • entry into cells other than phagocytes requires specific pathogen adaptations

  • methods of entry

    • internalization by host-pathogen binding

    • modulation of cytoskeleton

• intrinsic immune evasion

  • complement inhibition

  • modulation of phagocytosis

• humoral immune evasion

  • antigenic variability

• latency

• altering cell signaling

• evading host nutrient sequestration

Toxin production

• endotoxin: activates innate immune system

• exotoxin

Resisting treatment methods

• antibiotic resistance

• avoiding antibiotic exposure

• anthelmintic resistance

Biofilms

• the ultimate defense

  • avoids mechanical clearance

  • escapes host immune response

  • evades nutrient sequestration

  • resists treatment

How are biofilms formed?

• microbes attach to a surface reversibly

• bacteria grow and produce exopolymer

• bacterial metabolism creates nutrient gradients and opportunities for other bacteria

• complex community develops