--- module: 095-02 language: en chapter: 95 title: "Microbiome, Microbial Ecology, Evolution, and Host–Pathogen Co-adaptation" module_title: "Microbial evolution, horizontal gene transfer, virulence, and antimicrobial resistance" source_sha256: f774eda9421eda052e758c8ff7088a65f7ce0e15efbb71b69723576fd82cce43 --- # Microbial evolution and resistance ## Rapid evolution, variation, and selection ### Change visible within one infection or outbreak ### Large populations and short generation times ### Evolution is not intentional #### Random or imported variants persist if they reproduce more ### Mutation from replication or damage repair #### Most changes neutral or harmful #### A few alter targets, permeability, regulation, host range #### Antibiotics do not direct the useful mutation ### Selection enriches existing or new variants #### Subtherapeutic concentration at one site selects resistance ## Fitness cost and reversibility ### Costs from slow enzymes, transport, energy burden ### Compensatory mutations cut cost without restoring susceptibility ### Without drug pressure resistance may fall or persist ### Reducing use does not guarantee rapid reversal ## Horizontal gene transfer mechanisms ### Transfer independent of parent-to-offspring inheritance ### Transformation takes up naked environmental DNA ### Transduction moves genes by bacteriophage ### Conjugation transfers plasmids through cell contact ## Mobile genetic elements ### Plasmids are extrachromosomal replicons #### Persist via partitioning, addiction systems, selection #### Multi-resistance plasmids give co-selection ### Transposons move using transposases ### Integrons capture cassettes and express from a promoter ## Phage and microbial defence ### Phage act by predation, lysogeny, gene transfer ### Temperate phage integrate as prophage #### Confer toxins in diphtheria, cholera, Shiga systems ### CRISPR-Cas stores invader fragments #### RNA-guided nucleases cut matching nucleic acid #### Mobile elements evolve anti-CRISPR mechanisms ## Resistance mechanisms by drug class ### Destruction, target change, efflux, reduced entry, bypass ### Phenotype emerges from expression, permeability, inoculum, assay ### Beta-lactams inhibit penicillin-binding proteins #### Beta-lactamases, altered targets, porins, efflux #### Extended-spectrum enzymes versus carbapenemases #### Enzyme name alone cannot predict every drug ### Methicillin resistance uses a low-affinity binding protein ### Enterococcal vancomycin resistance replaces target chemistry ### Staphylococcal intermediate resistance thickens cell wall #### Same phenotype from distinct biology ### Aminoglycosides: modifying enzymes, methylation, uptake, efflux ### Fluoroquinolones: target mutation plus efflux and permeability ### Rifampicin: RNA polymerase change, rapid under monotherapy #### Link genotype to validated phenotype ## Tolerance, persistence, and testing ### Tolerance: survival without raised inhibitory concentration ### Persistence: small subpopulation surviving transient exposure ### Heteroresistance: resistant minority in a susceptible isolate #### These states cause relapse and buy evolutionary time ### Minimum inhibitory concentration under standard conditions ### Breakpoints use pharmacology, outcomes, distributions, standards #### Susceptible result does not guarantee success ### Method limits: diffusion, dilution, automated, molecular #### Molecular finds known determinants, not expression #### Genome prediction weakest for novel combinations ## Virulence and host damage ### Virulence is capacity to damage in a host context #### Adhesion, invasion, capsule, toxins, secretion systems #### A virulence gene does not prove current causation ### Pathogenicity islands show horizontal acquisition ### Secretion systems inject effectors ### Capsules block phagocytosis and complement ### Quorum sensing coordinates collective behaviour ### Damage is toxin, invasion, or immune mediated #### Superantigens broadly activate T cells #### Low-toxin organisms can still destroy tissue ## Within-host evolution, transmission, stewardship ### Within-host selection by immunity and drugs #### Parallel lineages adapt to biofilm and low oxygen #### One colony misrepresents diversity #### Relapse versus reinfection distinguished imperfectly ### Transmission adds a selection layer #### No universal trend toward benignity ### Stewardship keeps treatment effective, cuts needless selection #### Narrowest effective agent, optimised dose, source control #### Review at a set time and shorten duration #### Withholding needed early therapy is not stewardship ### One Health links humans, animals, water, soil #### Control needs many sectors together ### Evolution predictable in principle, contingent in detail #### Measure phenotype rather than trusting a name