--- module: 035-02 language: en chapter: 35 title: "Bacteria, Viruses, Fungi, Parasites, and Microbial Genetics" module_title: "Microbial strategy, ecological niches, and evolution under selection" source_sha256: a447f3780b898fe4f8dddae4dabd493442c6d6a534f410528ccd6220da0dbb98 --- # Microbial strategy, niches, and evolution under selection ## Architecture shapes clinical reasoning ### Architecture constrains ability and drug targets ### Fungi share eukaryotic machinery with humans #### Narrower selective toxicity ### Viruses expose step-specific targets ### Diagnose state, niche, burden, host relationship ## Bacterial envelope and drug access ### Wall-active drugs weaken the expanding structure #### Active growth important for killing ### Gram-positive: thick exposed wall, no outer membrane ### Gram-negative: thin wall behind outer membrane #### Porins restrict entry, pumps and enzymes reduce exposure #### Porin loss plus beta-lactamase: strong resistance ### Mycolic acids slow permeability, prolong treatment ### Mycoplasmas: no wall, beta-lactams fail ### Capsules inhibit complement and phagocytosis #### Opsonising antibody restores clearance #### Absent spleen: encapsulated bacteraemia dangerous ## Physiological state, biofilms, source control ### Abscess, phagolysosome, bone, biofilm slow growth #### Oxygen, iron, pH alter expression and susceptibility ### Persisters: transient phenotypic survivors #### Relapse from protected sites ### Biofilm: attachment, matrix, maturation #### Matrix limits immune access and diffusion #### Antibiotics fail to sterilise adherent reservoir ### Source control: drainage, debridement, device removal ### Persistent fever: reassess source before switching ### Suppressive therapy is distinct from eradication ## Viral tasks, tropism, and stability ### Positive-sense RNA acts directly as messenger ### Negative-sense viruses carry an RNA polymerase ### Retroviruses integrate, creating reservoirs ### Tropism needs more than a receptor #### Intracellular factors, temperature, access route ### Injury: cytopathic, immune, vascular, systemic ### Enveloped viruses fragile outside the body ### Non-enveloped capsids spread by surfaces, faecal-oral ### Tendencies, not sufficient infection-control rules ## Viral variation and selection ### Mutation, recombination, reassortment ### Most mutations neutral or harmful ### Selection enriches reproducing, transmitting variants ### Bottleneck passes a small subset ### Immune escape may compromise another property ### No intention, no guaranteed attenuation ## Fungal structure and dimorphism ### Chitin and glucan wall, ergosterol membrane ### Azoles, polyenes, echinocandins #### Activity varies by species and site ### Yeast in non-sterile sample may be colonisation #### Recovery from blood usually significant ### Invading hyphae prove disease more strongly ### Neutropenia: angioinvasion with little inflammation ### Dimorphic: mould outside, yeast after inhalation #### Geography and exposure are part of microbiology #### Impaired cellular immunity permits late dissemination ## Parasite life cycles ### Malaria: liver first, blood stage causes fever #### Dormant liver forms cause relapse #### Blood-stage treatment alone incomplete ### Thick films detect, thin films assess species ### Helminths: obstruction, migration, blood loss ### Eosinophilia tracks tissue migration ### Strongyloides autoinfection persists for decades #### Steroids trigger dissemination and sepsis #### Take exposure history before immune therapy ### Schistosome eggs drive granuloma and fibrosis ## Resistance and antimicrobial treatment ### Heritable variation meets selection and spread ### Target mutation, enzymes, pumps, permeability ### Horizontal transfer moves mechanisms together ### Genotype and phenotype are not identical ### Inhibitory concentration does not measure eradication ### Empirical choice: site, severity, host, history ### Narrow to the most limited effective option ### Duration matched to source control and response ## Specimens, microbiome, and causation ### Specimen quality limits what results show #### Squamous-rich sputum misses lower airway ### Blood cultures before antibiotics without delay ### Microbiome provides colonisation resistance ### Dysbiosis is descriptive, not causal ### Distinguish presence from pathogenic action #### Site, burden, invasion, timing strengthen cause ### Report method, site, burden, susceptibility ### Non-improvement: re-examine, do not escalate