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HomeNatureBrief antibiotic use drives human gut bacteria towards low-cost resistance

Brief antibiotic use drives human gut bacteria towards low-cost resistance

  • Hughes, D. & Andersson, D. I. Evolutionary trajectories to antibiotic resistance. Annu. Rev. Microbiol. 71, 579–596 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Murray, C. J. et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399, 629–655 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Lipsitch, M. & Samore, M. H. Antimicrobial use and antimicrobial resistance: a population perspective. Emerg. Infect. Dis. 8, 347–354 (2002).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Goossens, H., Ferech, M., Vander Stichele, R. & Elseviers, M. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 365, 579–587 (2005).

    Article 
    PubMed 

    Google Scholar
     

  • Sun, D. S. et al. Analysis of multiple bacterial species and antibiotic classes reveals large variation in the association between seasonal antibiotic use and resistance. PLoS Biol. 20, e3001579 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Marvig, R. L., Sommer, L. M., Jelsbak, L., Molin, S. & Johansen, H. K. Evolutionary insight from whole-genome sequencing of Pseudomonas aeruginosa from cystic fibrosis patients. Future Microbiol. 10, 599–611 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Olesen, S. W. et al. The distribution of antibiotic use and its association with antibiotic resistance. eLife 7, e39435 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stracy, M. et al. Minimizing treatment-induced emergence of antibiotic resistance in bacterial infections. Science 375, 889–894 (2022).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Long, D. R. et al. 2021 Young Investigator Award winner: anatomic gradients in the microbiology of spinal fusion surgical site infection and resistance to surgical antimicrobial prophylaxis. Spine 46, 143–151 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hegreness, M., Shoresh, N., Damian, D., Hartl, D. & Kishony, R. Accelerated evolution of resistance in multidrug environments. Proc. Natl Acad. Sci. USA 105, 13977–13981 (2008).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Toprak, E. et al. Evolutionary paths to antibiotic resistance under dynamically sustained drug selection. Nat. Genet. 44, 101–105 (2012).

    Article 
    CAS 

    Google Scholar
     

  • Lázár, V. et al. Bacterial evolution of antibiotic hypersensitivity. Mol. Syst. Biol. 9, 700 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rodriguez de Evgrafov, M., Gumpert, H., Munck, C., Thomsen, T. T. & Sommer, M. O. A. Collateral resistance and sensitivity modulate evolution of high-level resistance to drug combination treatment in Staphylococcus aureus. Mol. Biol. Evol. 32, 1175–1185 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Garoff, L. et al. Population bottlenecks strongly influence the evolutionary trajectory to fluoroquinolone resistance in Escherichia coli. Mol. Biol. Evol. 37, 1637–1646 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mahrt, N. et al. Bottleneck size and selection level reproducibly impact evolution of antibiotic resistance. Nat. Ecol. Evol. 5, 1233–1242 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lopatkin, A. J. et al. Clinically relevant mutations in core metabolic genes confer antibiotic resistance. Science 371, eaba0862 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Münch, P. C. et al. Pulsed antibiotic treatments of gnotobiotic mice manifest in complex bacterial community dynamics and resistance effects. Cell Host Microbe 31, 1007–1020.e4 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Vasquez, K. S. et al. Quantifying rapid bacterial evolution and transmission within the mouse intestine. Cell Host Microbe 29, 1454–1468.e4 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fung-Tomc, J. C. Correlation of in vitro and in vivo resistance development to antimicrobial agents. Antimicrobic Newsl. 7, 17–24 (1990).

    Article 
    CAS 

    Google Scholar
     

  • Jahn, L. J., Munck, C., Ellabaan, M. M. H. & Sommer, M. O. A. Adaptive laboratory evolution of antibiotic resistance using different selection regimes lead to similar phenotypes and genotypes. Front. Microbiol. 8, 816 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Relman, D. A. & Lipsitch, M. Microbiome as a tool and a target in the effort to address antimicrobial resistance. Proc. Natl Acad. Sci. USA 115, 12902–12910 (2018).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bottery, M. J., Pitchford, J. W. & Friman, V.-P. Ecology and evolution of antimicrobial resistance in bacterial communities. ISME J. 15, 939–948 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Tedijanto, C., Olesen, S. W., Grad, Y. H. & Lipsitch, M. Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora. Proc. Natl Acad. Sci. USA 115, E11988–E11995 (2018).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Browne, A. J. et al. Global antibiotic consumption and usage in humans, 2000–18: a spatial modelling study. Lancet Planet. Health 5, e893–e904 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Moradigaravand, D. et al. Prediction of antibiotic resistance in Escherichia coli from large-scale pan-genome data. PLoS Comput. Biol. 14, e1006258 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hicks, A. L. et al. Evaluation of parameters affecting performance and reliability of machine learning-based antibiotic susceptibility testing from whole genome sequencing data. PLoS Comput. Biol. 15, e1007349 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Redgrave, L. S., Sutton, S. B., Webber, M. A. & Piddock, L. J. V. Fluoroquinolone resistance: mechanisms, impact on bacteria, and role in evolutionary success. Trends Microbiol. 22, 438–445 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bush, N. G., Diez-Santos, I., Abbott, L. R. & Maxwell, A. Quinolones: mechanism, lethality and their contributions to antibiotic resistance. Molecules 25, 5662 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, X., Mariano, N., Rahal, J. J., Urban, C. M. & Drlica, K. Quinolone-resistant Haemophilus influenzae: determination of mutant selection window for ciprofloxacin, garenoxacin, levofloxacin, and moxifloxacin. Antimicrob. Agents Chemother. 48, 4460–4462 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Morgan-Linnell, S. K. & Zechiedrich, L. Contributions of the combined effects of topoisomerase mutations toward fluoroquinolone resistance in Escherichia coli. Antimicrob. Agents Chemother. 51, 4205–4208 (2007).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huseby, D. L. et al. Mutation supply and relative fitness shape the genotypes of ciprofloxacin-resistant Escherichia coli. Mol. Biol. Evol. 34, 1029–1039 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zlamal, J. E. et al. Shared and unique evolutionary trajectories to ciprofloxacin resistance in gram-negative bacterial pathogens. mBio 12, e00987-21 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhao, S. et al. Adaptive evolution within gut microbiomes of healthy people. Cell Host Microbe 25, 656–667.e8 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Poyet, M. et al. A library of human gut bacterial isolates paired with longitudinal multiomics data enables mechanistic microbiome research. Nat. Med. 25, 1442–1452 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Garud, N. R., Good, B. H., Hallatschek, O. & Pollard, K. S. Evolutionary dynamics of bacteria in the gut microbiome within and across hosts. PLoS Biol. 17, e3000102 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yaffe, E. & Relman, D. A. Tracking microbial evolution in the human gut using Hi-C reveals extensive horizontal gene transfer, persistence and adaptation. Nat. Microbiol. 5, 343–353 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Roodgar, M. et al. Longitudinal linked-read sequencing reveals ecological and evolutionary responses of a human gut microbiome during antibiotic treatment. Genome Res. 31, 1433–1446 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zlitni, S. et al. Strain-resolved microbiome sequencing reveals mobile elements that drive bacterial competition on a clinical timescale. Genome Med. 12, 50 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, D. W. & Garud, N. R. Rapid evolution and strain turnover in the infant gut microbiome. Genome Res. 32, 1124–1136 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fantin, B. et al. Ciprofloxacin dosage and emergence of resistance in human commensal bacteria. J. Infect. Dis. 200, 390–398 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dethlefsen, L. & Relman, D. A. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc. Natl Acad. Sci. USA 108, 4554–4561 (2011).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Maier, L. et al. Unravelling the collateral damage of antibiotics on gut bacteria. Nature 599, 120–124 (2021).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Truong, D. T., Tett, A., Pasolli, E., Huttenhower, C. & Segata, N. Microbial strain-level population structure and genetic diversity from metagenomes. Genome Res. 27, 626–638 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nielsen, H. et al. Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. Nat. Biotechnol. 32, 822–828 (2014).

    Article 

    Google Scholar
     

  • Nayfach, S., Shi, Z. J., Seshadri, R., Pollard, K. S. & Kyrpides, N. C. New insights from uncultivated genomes of the global human gut microbiome. Nature 568, 505–510 (2019).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nissen, J. N. et al. Improved metagenome binning and assembly using deep variational autoencoders. Nat. Biotechnol. 39, 555–560 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Quince, C. et al. DESMAN: a new tool for de novo extraction of strains from metagenomes. Genome Biol. 18, 181 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Smillie, C. S. et al. Strain tracking reveals the determinants of bacterial engraftment in the human gut following fecal microbiota transplantation. Cell Host Microbe 23, 229–240.e5 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Quince, C. et al. STRONG: metagenomics strain resolution on assembly graphs. Genome Biol. 22, 214 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Good, B. H. & Desai, M. M. Deleterious passengers in adapting populations. Genetics 198, 1183–1208 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Orillard, E. & Tan, M. Functional analysis of three topoisomerases that regulate DNA supercoiling levels in Chlamydia. Mol. Microbiol. 99, 484–496 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hirsch, J. & Klostermeier, D. What makes a type IIA topoisomerase a gyrase or a Topo IV? Nucleic Acids Res. 49, 6027–6042 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Helgesen, E., Sætre, F. & Skarstad, K. Topoisomerase IV tracks behind the replication fork and the SeqA complex during DNA replication in Escherichia coli. Sci. Rep. 11, 474 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhao, X. et al. Lethal action of quinolones against a temperature-sensitive dnaB replication mutant of Escherichia coli. Antimicrob. Agents Chemother. 50, 362–364 (2006).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rubin, D. H., Mortimer, T. D. & Grad, Y. H. Neisseria gonorrhoeae diagnostic escape from a gyrA-based test for ciprofloxacin susceptibility and the effect on zoliflodacin resistance: a bacterial genetics and experimental evolution study. Lancet Microbe 4, e247–e254 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Croucher, N. J. et al. Evidence for soft selective sweeps in the evolution of pneumococcal multidrug resistance and vaccine escape. Genome Biol. Evol. 6, 1589–1602 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ghosh, O. M. & Good, B. H. Emergent evolutionary forces in spatial models of luminal growth and their application to the human gut microbiota. Proc. Natl Acad. Sci. USA 119, e2114931119 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Andersson, D. I. & Hughes, D. Antibiotic resistance and its cost: is it possible to reverse resistance? Nat. Rev. Microbiol. 8, 260–271 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Marcusson, L. L., Frimodt-Møller, N. & Hughes, D. Interplay in the selection of fluoroquinolone resistance and bacterial fitness. PLoS Pathog. 5, e1000541 (2009).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yao, H. et al. Emergence of a potent multidrug efflux pump variant that enhances Campylobacter resistance to multiple antibiotics. mBio 7, e01543-16 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Baker, S. et al. Fitness benefits in fluoroquinolone-resistant Salmonella typhi in the absence of antimicrobial pressure. eLife 2, e01229 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kent, A. G., Vill, A. C., Shi, Q., Satlin, M. J. & Brito, I. L. Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C. Nat. Commun. 11, 4379 (2020).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bishara, A. et al. High-quality genome sequences of uncultured microbes by assembly of read clouds. Nat. Biotechnol. 36, 1067–1075 (2018).

    Article 
    CAS 

    Google Scholar
     

  • Suzuki, Y. et al. Long-read metagenomic exploration of extrachromosomal mobile genetic elements in the human gut. Microbiome 7, 119 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Moss, E. L., Maghini, D. G. & Bhatt, A. S. Complete, closed bacterial genomes from microbiomes using nanopore sequencing. Nat. Biotechnol. 38, 701–707 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Edlund, C., Lindqvist, L. & Nord, C. E. Norfloxacin binds to human fecal material. Antimicrob. Agents Chemother. 32, 1869–1874 (1988).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schmieder, R. & Edwards, R. Fast identification and removal of sequence contamination from genomic and metagenomic datasets. PLoS ONE 6, e17288 (2011).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, D., Liu, C. M., Luo, R., Sadakane, K. & Lam, T. W. MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph. Bioinformatics 31, 1674–1676 (2014).

    Article 

    Google Scholar
     

  • Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinf. Oxford Acad. 25, 1754–1760 (2009).

    CAS 

    Google Scholar
     

  • Kang, D. D. et al. MetaBAT 2: an adaptive binning algorithm for robust and efficient genome reconstruction from metagenome assemblies. PeerJ 7, e7359 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mende, D. R. et al. proGenomes2: an improved database for accurate and consistent habitat, taxonomic and functional annotations of prokaryotic genomes. Nucleic Acids Res. 48, D621–D625 (2019).

    ADS 
    PubMed Central 

    Google Scholar
     

  • Parks, D. H., Imelfort, M., Skennerton, C. T., Hugenholtz, P. & Tyson, G. W. CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes. Genome Res. 25, 1043–1055 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chaumeil, P.-A., Mussig, A. J., Hugenholtz, P. & Parks, D. H. GTDB-Tk v2: memory friendly classification with the genome taxonomy database. Bioinformatics 38, 5315–5316 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schliep, K. P. phangorn: phylogenetic analysis in R. Bioinformatics 27, 592–593 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hyatt, D. et al. Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinf. 11, 119 (2010).

    Article 

    Google Scholar
     

  • Buchfink, B., Xie, C. & Huson, D. H. Fast and sensitive protein alignment using DIAMOND. Nat. Methods 12, 59–60 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Steinegger, M. & Söding, J. MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets. Nat. Biotechnol. 35, 1026–1028 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Huerta-Cepas, J. et al. eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses. Nucleic Acids Res. 47, D309–D314 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sievers, F. et al. Fast, scalable generation of high‐quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hartl, D. L. & Clark, A. G. Principles of Population Genetics (Sinauer Associates, 2007).


    Google Scholar
     

  • Kinde, I., Wu, J., Papadopoulos, N., Kinzler, K. W. & Vogelstein, B. Detection and quantification of rare mutations with massively parallel sequencing. Proc. Natl Acad. Sci. USA 108, 9530–9535 (2011).

    Article 
    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yaffe, E. eitanyaffe/PolyPanner: PolyPanner 1.0.2. Zenodo https://doi.org/10.5281/zenodo.14775630 (2025).

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