Key Concepts in Microbiology and Infectious Diseases

Describe the lifecycle of Plasmodium

Sporozoite → hepatic schizont → merozoite → erythrocytic trophozoite → schizont → gametocyte

Describe the mechanism of action of Artemisinin and what disease it treats

• Artemisinin is an antimalarial drug

• Direct molecular damage:

  • acts by generating reactive oxygen species in the food vacuole of the malaria parasite, leading to damage of essential biomolecules (e.g. proteins, lipids, membranes) and ultimately resulting in the rapid death of the blood-stage parasites.

• Interference with haeme clearance:

  • Artemisinin radicals form covalent adducts with haeme, blocking the parasite’s haeme detoxification pathway and amplifying oxidative stress

PfEMP1

Mediates cytoadherence of infected RBCs to endothelium, avoiding splenic clearance and causing microvascular occlusion

P. vivax relapse

P. vivax forms dormant hypnozoites in hepatocytes, causing relapses months later

HRP2-based lateral-flow assay

Detecting P. falciparum antigen in blood

EHEC toxin

Shiga-like toxin inhibits 60S ribosome → HUS

ETEC toxin

Heat-labile/stable toxins ↑ cAMP/cGMP → secretory diarrhea

Type 1 and P fimbriae

Mediate adhesion to uroepithelial cells

K1 capsule

Inhibits complement deposition and MAC formation on bacterial surface

O157:H7 virulence locus

Pathogenicity island carrying Shiga-like toxin genes and T3SS components

TLR4

On innate immune cells binds LPS → NF-κB activation

Pneumolysin

Lyses host cells, activates complement, and induces inflammation

Asplenic patients

They lack splenic macrophages and marginal-zone B cells needed to clear encapsulated bacteria

Pneumococcal capsule

Inhibits opsonin binding and prevents complement C3b deposition

Autolysin (LytA)

Cleaves cell wall, releasing inflammatory components

IgA1 protease

Cleaves IgA hinge region, allowing mucosal attachment

Tuberculous granuloma

Caseating necrotic core surrounded by epithelioid macrophages, Langhans giant cells, lymphocytes, and fibroblasts

ESX-1 secretion system

Secretes ESAT-6 and CFP-10, which disrupt phagosomal membrane and aid cytosolic escape

Cord factor

Induces TNF-α, causes granuloma necrosis, and inhibits neutrophil migration

IGRA test

Detects IFN-γ release by T cells in response to ESAT-6/CFP-10 peptides

M. tuberculosis acid-fast

Mycolic acids in the cell wall retain carbol fuchsin dye during acid-alcohol wash

Lytic cycle

Phage replicates, lyses host

Lysogenic cycle

Phage DNA integrates as prophage, replicates with host

Generalized transduction

Random bacterial DNA packaged into phage capsid and transferred to new host

Phage therapy

Targets antibiotic-resistant bacteria and can disrupt biofilms

Prophage induction

DNA damage (e.g. UV) activates SOS response, cleaves phage repressor, triggering lytic cycle

CRISPR defense

Integrate phage DNA snippets into CRISPR array → guide RNAs direct Cas nucleases to destroy matching phage DNA

viral quasispecies

A cloud of genetically diverse but related genomes generated by high-error RdRp, enabling rapid adaptation

antigenic drift

Point mutations accumulate slowly

antigenic shift

Reassortment of segments between strains → novel HA/NA combos

drivers of viral emergence

Zoonotic spillover, global travel, ecological disruption (deforestation, climate change)

R₀

Basic reproduction number; R₀ > 1 → epidemic potential; R₀ < 1 → outbreak dies out

reassortment

Swap entire genome segments

recombination

Exchange of nucleotide sequences within a genome

Trypanosoma brucei antigenic variation

Periodic switching of Variant Surface Glycoprotein (VSG) genes to evade antibody response

T. brucei transmission

Tsetse fly → African sleeping sickness

T. cruzi transmission

Reduviid bug → Chagas disease (cardiomyopathy)

kinetoplast DNA

Network of interlocked minicircles & maxicircles in trypanosome mitochondrion essential for gene expression

diagnosis of African trypanosomiasis

Detection of trypomastigotes in blood smear or CSF by microscopy

glycosomes

Peroxisome-like organelles compartmentalizing glycolytic enzymes for rapid ATP production

common HAI pathogens

MRSA (mecA β-lactam resistance), VRE (vanA D-Ala-D-Lac target), P. aeruginosa (efflux pumps)

C. difficile persistence

Spores resist disinfectants and germinate when microbiota are disrupted

catheter-associated biofilm formation

Pili & exopolysaccharide matrix protect bacteria from antibiotics and immunity

van gene for vancomycin resistance

vanA operon encodes ligase that synthesizes D-Ala-D-Lac termini

prevent MRSA spread

Contact precautions, hand hygiene, decolonization, environmental cleaning

toxoplasmosis lifecycle in humans

Ingest oocysts or tissue cysts → tachyzoites disseminate → bradyzoite cysts in brain/muscle

congenital defects from fetal infection

Hydrocephalus, intracranial calcifications, chorioretinitis

T. gondii host immunity manipulation

Inhibits apoptosis & modulates cytokine responses to establish chronic infection

diagnosis of acute toxoplasmosis

Serology: detection of IgM and rising IgG titers

HIV patients risk for toxoplasmic encephalitis

CD4+ T cell loss allows reactivation of bradyzoite cysts in CNS

incidence vs prevalence

Incidence: new cases/time; Prevalence: total cases at a point in time

herd immunity threshold

Proportion immune needed to prevent sustained transmission = 1 - 1/R₀

attack rate calculation

(New cases during outbreak / Population at risk) × 100%

case-fatality rate

(Deaths from disease / Confirmed cases) × 100%

R₀ > 1 significance

Each case infects >1 person → potential epidemic spread

horizontal gene transfer

Accelerates bacterial adaptation.

Acquisition of novel genes

Acquisition of novel genes (via conjugation, transformation, transduction) bypasses slow point mutations, enabling instant new traits.

Muller's ratchet

Irreversible accumulation of deleterious mutations in asexual lineages reduces fitness over time without recombination.

Clonal interference

Competition among different beneficial mutations in separate clones slows overall adaptation in large asexual populations.

Genome reduction in endosymbionts

Loss of genes dispensable inside host cells streamlines the genome for a host-dependent lifestyle.

Lenski's Long-Term Evolution Experiment

E. coli populations evolved increased fitness, novel traits (like citrate utilization), and parallel mutations over tens of thousands of generations.

Sigma-factor specificity

Sigma factors redirect RNAP to stress-response promoters.

Two-component systems

Two-component systems sense extracellular cues via sensor kinase and response regulator.

Riboswitch

Ligand binding alters mRNA secondary structure to form a terminator or sequester the ribosome binding site, toggling transcription/translation.

Catabolite repression of the lac operon

High glucose → low cAMP → CRP-cAMP dissociates from lac promoter → lac operon transcription blocked until glucose is gone.

Small RNAs (sRNAs)

Base-pair with target mRNAs to block ribosome binding or recruit RNases, fine-tuning stress and virulence gene expression.

Regulon

Regulon: operons controlled by one TF.

Stimulon

Stimulon: all regulons responding to a specific stimulus (e.g. heat shock).

DnaA's role

DnaA-ATP binds oriC to unwind DNA and recruit replisome.

RIDA and datA sites

RIDA and datA sites hydrolyze DnaA-ATP to prevent early re-initiation.

Theta replication

Theta: bidirectional forks on circular chromosome.

Rolling-circle replication

Rolling-circle: unidirectional nick generates concatemeric DNA in some plasmids/phages.

Tus-Ter complex

Tus bound to Ter sites stalls replication forks in one direction, ensuring forks meet in the termination zone.

SeqA

Binds hemimethylated oriC after replication, blocking DnaA access until Dam methylase restores full methylation.

Cytokinetic Z-ring

FtsZ polymerizes into a midcell ring, recruiting division machinery for septum synthesis and cell scission.

Replication strategies of (+)ssRNA, (-)ssRNA, and dsDNA viruses

(+)ssRNA: genome = mRNA. (-)ssRNA: carry RdRp to make mRNA. dsDNA: use host RNAP in nucleus; some bring own enzymes.

Enveloped viruses budding

Viral matrix proteins and glycoproteins cluster at membrane, induce curvature, and scission releases virion with host-derived envelope.

Viroporin

Virus-encoded ion channel in host membranes that alters permeability to aid assembly or release of progeny virions.

Poxviruses replication

Carry their own polymerases, capping and polyadenylation enzymes in the virion, bypassing the need for nuclear machinery.

DNA viruses assembly in the nucleus

They depend on host DNA polymerases and splicing factors, which are only available in the nucleus.

Dynamic population of closely related genomes

Generated by high-error RdRp, enabling rapid adaptation to host or drug pressures.

Major drivers of viral emergence

Zoonotic spillover, global travel/trade, ecological change (e.g. deforestation, climate warming).

Gram-positive envelopes

Thick peptidoglycan, teichoic acids.

Gram-negative envelopes

Thin peptidoglycan, outer membrane with LPS, periplasmic space.

Fungal chitin

Provides tensile strength.

β-glucans

Form crosslinked matrix for rigidity and porosity.

LPS and septic shock

Lipid A engages TLR4 on macrophages → massive TNFα/IL-1 release → systemic vasodilation and organ failure.

Echinocandins

Inhibit fungal β-1,3-glucan synthase, weakening the cell wall; high specificity with low human toxicity.

Bacterial S-layer function

Crystalline protein layer on some bacteria for protection against environmental stress and host immunity.

Polyprotein strategy in (+)ssRNA viruses

Single ORF yields large polyprotein, then viral proteases cleave it into multiple functional proteins.

Cap-snatching

Endonuclease cleaves 5′ caps from host mRNAs to prime viral mRNA synthesis (e.g. influenza).

IRES-mediated translation

Internal ribosome entry sites bypass cap recognition, recruiting ribosomes directly for cap-independent initiation.

Leaky scanning

Ribosomes bypass weak Kozak-context AUGs to initiate at downstream start sites, producing protein isoforms.

−1 ribosomal frameshifting in retroviruses

Slippery sequence + downstream pseudoknot cause ribosome to shift −1, generating Gag-Pol fusion necessary for replication.

+ssRNA viruses and membrane-associated replication complexes

Concentrates polymerases, hides dsRNA from host sensors, and provides lipid environment optimal for replication.

Rough ER functions

Ribosome-bound: secreted/membrane protein synthesis.

Smooth ER functions

Lipid synthesis, detoxification, Ca²⁺ storage.

Peroxisomes and innate immunity

Generate reactive oxygen species to degrade invading microbial components.

Endosomal acidification in viral entry

Low pH triggers conformational changes in viral fusion proteins (e.g. influenza HA) to penetrate host membranes.

Golgi's role in viral glycoprotein maturation

Processes and glycosylates viral envelope proteins before trafficking to budding sites.