TABLE 1.

The components shaping pathways and trajectories in the evolution of antibiotic resistance^a

Component type	Components
Evolutionary objects	Antibiotic molecular targets, antibiotic transporters, single and supraprotein domains, rRNA sequences, intrinsic resistance genes, regulators of antibiotic transporters and resistance genes, stress response networks, acquired AbR genes, noncoding segments of genome, random chromosomal sequences, genes with epistatic relations with AbR, contingency loci, operons, insertion sequences, small intergenic repetitive sequences, gene cassettes, integrons, transposons, plasmids, integrative-conjugative elements, genetic islands, bacteriophages, bacterial species, bacterial subspecies, bacterial clones (genomotypes, STs), clonal ensembles, genetic exchange communities, metagenomotypes (i.e., enterotypes), resistomes (intrinsic and mobile)
Evolutionary processes	Growth, mutation, genetic diversification, epigenetic epistasis, fitness cost and cost compensation, gene amplification, gene conversion, gene redundancy, gene promiscuity by HGT, gene recombination, gene insertions and deletions, gene silencing, gene degeneracy, gene decontextualization by HGT, promoter recombination, genome recombination, gene conjugation, gene transformation, gene transduction, transfer by extracellular vesicles or nanotubes, MGE transmission, MGE-host interactions, MGE mobilization, MGE recombination, MGE copy no., MGE maintenance, MGE incompatibility, bacterium-bacterium contacts and recognition, bacterial antagonism and cooperation, interhost transmission, host-bacterium interactions, microbiota coalescence
Evolutionary mechanisms	Selection by other reasons than AbR, selection dependent on AbR, cross-selection, coselection, selection in antibiotic gradients, random drift, random draft, gene hitchhiking, neofunctionalization-exaptation, founder effects, persistence, tolerance, inducibility of AbR, resilience in the presence of Ab, changes in fitness, niche exploitation and coexploitation, niche construction, habitat compartmentalization, spatial structuration, transmission, dispersal, clonal shifts, clonal waves, clonal bunch selection, reticulation of evolutionary trajectories
Evolutionary drivers	Bacterial stress, bacterial bottlenecks, human antibiotic consumption, animal antibiotic consumption, agricultural antibiotic consumption, historical antibiotic use, antibiotic pharmacokinetics/dynamics, collateral susceptibility and resistance, human and animal factors (age, health, and nutrition), bacterial transmission, hygiene, sanitation, crowded human or animal populations, water and sludge reuse, antibiotics and biocides in the environment, pollution with heavy metals, environmental pollution with human and animal bacteria, decrease in animal and global biodiversity, environmental variation, global warming, social norms for the use of antibiotics, social norms for environmental health

^aEvolutionary objects are the biological substrates, from proteins to microbiotas, on which evolutionary processes act, producing phenotypes, whose frequency is governed by evolutionary mechanisms, which are under the influence of evolutionary drivers. MGE, mobile genetic elements; AbR, antibiotic resistance.