Chapter 23 Omega

Pathogen

An organism (virus, bacterium, fungus, or parasite) that colonizes a host and can cause disease by exploiting host resources.

Microbiota

The collection of microbial species (bacteria, fungi, viruses, protozoa) that normally live on and in a host, often without causing disease and sometimes providing benefits.

Primary pathogen

A microbe that can cause disease in healthy, nonimmune hosts.

Opportunistic pathogen

A microbe that causes disease only when host defenses are weakened or other conditions allow (e.g., immunosuppression, wound).

Successful-pathogen functions

To cause infection a pathogen must (1) enter the host, (2) find a nutritionally compatible niche, (3) avoid or subvert innate and adaptive immunity, (4) replicate, and (5) exit and transmit to new hosts.

Gram-positive bacteria

Bacteria with a thick peptidoglycan cell wall (retains Gram stain) outside a single membrane.

Gram-negative bacteria

Bacteria with a thinner peptidoglycan layer plus an outer membrane that contains lipopolysaccharide (LPS).

LPS (lipopolysaccharide)

A major component of Gram-negative outer membranes

PAMPs (pathogen-associated molecular patterns)

Microbial molecules (e.g., peptidoglycan, LPS, dsRNA) recognized by host innate immune receptors.

Facultative pathogen

A microbe that can live and replicate both inside a host and in environmental reservoirs (soil, water).

Obligate pathogen

A microbe that requires a host for replication and cannot complete its life cycle in the external environment.

Virulence gene

A bacterial gene whose product contributes to the organism’s ability to cause disease (not required for basic growth).

Virulence factor

The protein or molecule encoded by a virulence gene (toxins, adhesins, secretion-system effectors).

Pathogenicity island

A cluster of virulence genes in the genome, often acquired by horizontal transfer.

Horizontal gene transfer (HGT)

Movement of genetic material between organisms by non-vertical means, enabling rapid acquisition of traits (e.g., virulence).

Natural transformation

HGT mechanism in which bacteria take up free DNA from the environment and incorporate it.

Transduction

HGT mediated by bacteriophages that package and transfer bacterial DNA.

Conjugation

HGT via direct cell–cell transfer of plasmids or DNA through a conjugation pilus.

Core genome

Genes shared by all strains of a bacterial species (essential/housekeeping).

Pangenome

The full set of genes found across all strains of a species (core + accessory/pathogenicity genes).

Genomic variation within a species

Strains can differ dramatically (e.g., E. coli strains may vary by ~25% of their genomes), due largely to HGT.

Toxin A–B architecture

Many bacterial toxins have a B (binding) subunit that targets host-cell receptors and an A (active) subunit with enzymatic activity that perturbs host signaling.

Cholera-toxin entry & action

Cholera toxin B binds intestinal receptors and delivers an A subunit that ADP-ribosylates Gs → constitutive adenylyl cyclase activation → massive cAMP → Cl⁻/water secretion → diarrhea.

Anthrax-toxin entry & action

Bacillus anthracis secreted B-subunit(s) bind receptors to translocate two A subunits (edema factor, an adenylate cyclase, and lethal factor, a protease) into host cells, disrupting signaling and immune function.

Secretion systems (general)

Bacterial multiprotein machines that deliver effector proteins to the extracellular milieu or directly into host cells (contact-dependent delivery).

Type III secretion system (T3SS)

A syringe-like needle in many Gram-negative bacteria that injects unfolded effector proteins directly into host-cell cytosol

Type IV secretion system (T4SS)

A versatile translocation apparatus related to conjugation machinery that transfers proteins and/or DNA into host cells.

Dimorphism (pathogenic fungi)

The ability of some fungi to grow in two forms (yeast ↔ filamentous/mold)

Malaria parasite lifecycle (overview)

Plasmodium alternates between mosquito and human stages — sporozoites injected by mosquito → liver stage → blood-stage merozoites that infect RBCs (symptoms) → gametocytes taken up by mosquito where sexual reproduction occurs.

Viral morphologies

Viruses can be helical, icosahedral, complex/irregular or very large

Capsid

Protein shell that encloses the viral genome (sometimes called nucleocapsid when genome + capsid).

Envelope

A host-derived lipid bilayer surrounding some virions that contains inserted viral glycoproteins.

Envelope acquisition

Enveloped viruses bud through host-cell membranes (plasma membrane or internal membranes) and obtain a lipid bilayer studded with viral envelope proteins.

Six general viral requirements

(1) attach to susceptible host cells, (2) enter and uncoat, (3) replicate the genome, (4) express viral proteins, (5) assemble progeny virions, and (6) exit and transmit while evading host defenses.

Four viral entry strategies (common)

(1) receptor-mediated endocytosis (clathrin or other routes), (2) macropinocytosis (large-particle uptake), (3) direct fusion of viral envelope with plasma or endosomal membrane (often pH-triggered), (4) pore-formation or capsid-mediated genome translocation for nonenveloped viruses.

Endosomal fusion (pH-triggered)

Enveloped viruses sense endosomal acidification → conformational change in fusion protein → fusion of viral and endosomal membranes and genome release.

Macropinocytosis

Virus induces actin-driven membrane ruffling and large vesicle uptake (used by some large viruses).

Pore-formation/nonenveloped entry

Nonenveloped viruses undergo capsid rearrangements that create a membrane pore to translocate genome into the cytosol.

Entry-by-zipper mechanism

Pathogen surface adhesins bind host receptors tightly and progressively “zip” the host membrane around the pathogen for uptake (e.g., Listeria internalins).

Entry-by-trigger mechanism

Pathogen injects or secretes effectors that globally activate actin remodeling and membrane ruffling to induce macropinocytic uptake (e.g., Salmonella, Shigella).

Yersinia pestis transmission strategy

Y. pestis multiplies in flea foregut and forms a blockage that causes repeated failed feedings, forcing the flea to regurgitate bacteria into bite wounds and thereby transmit plague.

H. pylori persistence and discovery

H. pylori survives stomach acidity by using flagella to reach the less acidic mucus/epithelial surface and urease to locally neutralize acid (urea → ammonia). Discovery: Barry Marshall and colleagues proved causation by isolating the bacterium and — famously — Marshall ingested a culture, developed gastritis, and was cured with antibiotics, supporting H. pylori as the cause of many ulcers.

Adhesins and pili

Surface proteins (adhesins) often at pilus tips mediate tight binding to host glycoconjugates or receptors and determine tissue tropism (e.g., E. coli pili binding kidney vs bladder epithelia).

Bordetella pertussis mechanism

Adheres to ciliated respiratory epithelial cells via adhesins and secretes pertussis toxin (an A–B toxin) that ADP-ribosylates Gi → increased cAMP and impaired immune signaling → ciliated-cell death and disrupted mucus clearance → coughing and transmission.

EPEC (enteropathogenic E. coli) mechanism

Uses a T3SS to translocate Tir into enterocyte membranes

HIV entry & coreceptor use

HIV binds CD4 on helper T cells/macrophages then engages a chemokine co-receptor (CCR5 or CXCR4) to trigger membrane fusion and entry

CCR5-Δ32 resistance

A human mutation (32-bp deletion) in CCR5 that disrupts receptor expression confers strong resistance or reduced susceptibility to CCR5-tropic HIV strains in homozygous individuals.

Toxoplasma gondii invasion

T. gondii deploys a conoid and secreted effectors (from specialized organelles) to form a moving junction, actively propels itself through that ring using its actomyosin cytoskeleton, and becomes enclosed in a nonfusogenic parasitophorous vacuole that avoids lysosomal fusion.

Trypanosoma cruzi entry strategies

Lysosome-dependent pathway: parasite triggers host Ca²⁺ signaling, recruits lysosomes that fuse with plasma membrane and allow parasite entry into a lysosome-like vacuole

Intracellular pathogen lysosome-escape strategies

Intracellular pathogens escape lysosomal destruction by leaving the phagosome and entering the cytosol, blocking or delaying phagosome–lysosome fusion, modifying the vacuole to prevent fusion, or resisting the harsh lysosomal environment. Many pathogens use actin-based movement to travel through the cytoplasm and spread between cells without exposure to antibodies.

Listeria monocytogenes phagosome escape

L. monocytogenes escapes the phagosome by inducing actin polymerization at one pole, generating actin comet tails that propel it through the cytosol. This movement pushes it into neighboring cells through membrane protrusions, allowing spread without extracellular exposure.

Salmonella enterica phagosome evasion

S. enterica uses a type III secretion system to inject effectors into host cells. These effectors activate Rho GTPases, cause actin rearrangements, and induce membrane ruffling. The ruffles fold over the bacteria and engulf them into modified vacuoles that avoid normal lysosomal fusion.

Mycobacterium tuberculosis phagosome evasion

M. tuberculosis prevents normal phagosome–lysosome fusion by altering trafficking signals on its vacuole, allowing it to survive within an unfused, modified phagosomal compartment.

Legionella pneumophila phagosome evasion

L. pneumophila remodels its vacuole into a unique compartment that avoids lysosomal fusion by recruiting ER-derived membranes and manipulating host trafficking pathways.

Viral envelope acquisition strategies

Enveloped viruses obtain membranes by budding through host organelles or the plasma membrane. During budding, viral proteins inserted into host membranes package the viral genome inside a host-derived lipid envelope.

Actin-based movement of pathogens

Several pathogens, including Listeria, Shigella, Rickettsia, Burkholderia, Ebola virus, and baculovirus, induce actin nucleation at one pole of the microbe. Actin filament growth pushes them through the cytosol and into neighboring cells.

Actin nucleation mechanisms in bacteria

Different pathogens use distinct mechanisms: Listeria and baculovirus activate Arp2/3 directly

Microtubule-based viral movement

Many viruses exploit microtubules for long-distance travel within cells. Neurotropic viruses bind dynein for retrograde transport toward the nucleus and use kinesin for anterograde transport back to axon terminals after replication.

Microbial manipulation of autophagy

Some microbes avoid antimicrobial autophagy by shielding themselves or escaping into the cytosol. Others exploit autophagy to obtain nutrients or expand their vacuoles. Examples include Francisella avoiding recognition, Listeria escaping capture, Coxiella recruiting autophagosomes, and poliovirus using autophagy for membrane trafficking and release.

Pathogen advantages enabling rapid evolution

Pathogens evolve quickly because they replicate at extremely high rates and experience strong selective pressures from the host immune system and antimicrobial drugs. This rapid mutation and selection allow new variants to emerge frequently.

Antigenic variation in trypanosomes

Trypanosoma brucei evades immunity by frequently switching its surface VSG protein. It contains ~1000 silent VSG genes and repeatedly rearranges them into active expression sites, producing new antigenic variants that escape antibody clearance and cause recurring waves of infection.

Error-prone viral replication

Viral replication is highly error-prone because many viral polymerases lack proofreading. This generates frequent mutations, rapidly producing diverse viral populations and enabling fast adaptation to drugs and immune pressure.

Evolution of pandemic influenza strains

Influenza viruses have segmented RNA genomes. When two strains infect the same host, segments reassort to form new hybrid viruses. These reassorted strains can acquire avian genes, cross species barriers, and cause pandemics, as seen in 1918 and 2009.

Antibiotic targets displaying selective toxicity

Antibiotics target bacterial-specific pathways such as cell-wall synthesis, DNA replication, transcription, translation, and unique metabolic processes. These pathways differ from eukaryotic host processes, allowing selective inhibition of bacteria.

Three mechanisms of antibiotic resistance

Pathogens resist antibiotics by (1) altering the drug’s target so the drug no longer binds, (2) producing enzymes that modify or destroy the drug, or (3) preventing drug access by pumping it out or reducing permeability.

Definitions of pathogen, microbiota, normal flora, microbiome, mutualism, commensalism, and parasitism

A pathogen is an organism that causes disease. Microbiota/normal flora are the microorganisms normally living on or in the body. The microbiome is the collective genomes of these microbes. Mutualism benefits both host and microbe. Commensalism benefits the microbe without harming the host. Parasitism benefits the microbe while harming the host.

Benefits humans receive from their microbiome

The human microbiome helps digest food, synthesizes vitamins, supports immune development, prevents pathogen colonization, and provides a reservoir of beneficial genes that aid metabolism and defense.