Abstract
The antibiotic cefiderocol hijacks iron transporters to facilitate its uptake and resists β-lactamase degradation. While effective, resistance has been detected clinically with unknown mechanisms. Here, using experimental evolution, we identified cefiderocol resistance mutations in Pseudomonas aeruginosa. Resistance was multifactorial in host-mimicking growth media, led to multidrug resistance and paid fitness costs in cefiderocol-free environments. However, kin selection drove some resistant populations to cross-protect susceptible individuals from killing by increasing pyoverdine secretion via a two-component sensor mutation. While pyochelin sensitized P. aeruginosa to cefiderocol killing, pyoverdine and the enterobacteria siderophore enterobactin displaced iron from cefiderocol, preventing uptake by susceptible cells. Among 113 P. aeruginosa intensive care unit clinical isolates, pyoverdine production directly correlated with cefiderocol tolerance, and high pyoverdine producing isolates cross-protected susceptible P. aeruginosa and other Gram-negative bacteria. These in vitro data show that antibiotic cross-protection can occur via degradation-independent mechanisms and siderophores can serve unexpected protective cooperative roles in polymicrobial communities.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Data availability
RNA, whole-genome population and colony sequencing data are accessible in the NCBI SRA under accession number PRJNA971207. Genome sequencing data for the clinical isolates are available in the NCBI SRA under the accession number PRJNA934930. Confocal micrographs are available at https://doi.org/10.6084/m9.figshare.24898107. The reference genome sequence of P. aeruginosa PAO1 is available from GenBank, with accession number NC_002516. Source data are provided with this paper.
References
Huemer, M., Mairpady Shambat, S., Brugger, S. D. & Zinkernagel, A. S. Antibiotic resistance and persistence—implications for human health and treatment perspectives. EMBO Rep. 21, e51034 (2020).
Tacconelli, E. et al. Surveillance for control of antimicrobial resistance. Lancet Infect. Dis. 18, e99–e106 (2018).
Nathwani, D., Raman, G., Sulham, K., Gavaghan, M. & Menon, V. Clinical and economic consequences of hospital-acquired resistant and multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis. Antimicrob. Resist. Infect. Control 3, 32 (2014).
Mittal, R., Aggarwal, S., Sharma, S., Chhibber, S. & Harjai, K. Urinary tract infections caused by Pseudomonas aeruginosa: a minireview. J. Infect. Public Health 2, 101–111 (2009).
Ferreiro, J. L. L. et al. Pseudomonas aeruginosa urinary tract infections in hospitalized patients: mortality and prognostic factors. PLoS ONE 12, e0178178 (2017).
Cystic Fibrosis Foundation Patient Registry—2020 Annual Data Report (Cystic Fibrosis Foundation, 2021).
Aoki, T. et al. Cefiderocol (S-649266), a new siderophore cephalosporin exhibiting potent activities against Pseudomonas aeruginosa and other Gram-negative pathogens including multi-drug resistant bacteria: structure activity relationship. Eur. J. Med. Chem. 155, 847–868 (2018).
Moynié, L. et al. Structure and function of the PiuA and PirA siderophore–drug receptors from Pseudomonas aeruginosa and Acinetobacter baumannii. Antimicrob. Agents Chemother. 61, e02531–16 (2017).
Ito, A. et al. Siderophore cephalosporin cefiderocol utilizes ferric iron transporter systems for antibacterial activity against Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 60, 7396–7401 (2016).
Luscher, A. et al. TonB-dependent receptor repertoire of Pseudomonas aeruginosa for uptake of siderophore–drug conjugates. Antimicrob. Agents Chemother. 62, e00097–18 (2018).
Ito, A. et al. In vitro antibacterial properties of cefiderocol, a novel siderophore cephalosporin, against Gram-negative bacteria. Antimicrob. Agents Chemother. 62, e01454-17 (2017).
Ito, A. et al. 696. Mechanism of cefiderocol high MIC mutants obtained in non-clinical FoR studies. Open Forum Infect. Dis. 5, S251 (2018).
Courvalin, P. Why is antibiotic resistance a deadly emerging disease? Clin. Microbiol. Infect. 22, 405–407 (2016).
Streling, A. P. et al. Evolution of cefiderocol non-susceptibility in Pseudomonas aeruginosa in a patient without previous exposure to the antibiotic. Clin. Infect. Dis. https://doi.org/10.1093/cid/ciaa1909 (2021).
Tamma, P. D. et al. Comparing the activity of novel antibiotic agents against carbapenem-resistant Enterobacterales clinical isolates. Infect. Control Hosp. Epidemiol. https://doi.org/10.1017/ice.2022.161 (2022).
Simner, P. J. et al. Cefiderocol activity against clinical Pseudomonas aeruginosa isolates exhibiting ceftolozane–tazobactam resistance. Open Forum Infect. Dis. 8, ofab311 (2021).
Ikawa, S., Yamasaki, S., Morita, Y. & Nishino, K. Role of the drug efflux pump in the intrinsic cefiderocol resistance of Pseudomonas aeruginosa. Preprint at bioRxiv https://doi.org/10.1101/2022.05.31.494263 (2022).
Gomis-Font, M. A., Sastre-Femenia, M. À., Taltavull, B., Cabot, G. & Oliver, A. In vitro dynamics and mechanisms of cefiderocol resistance development in wild-type, mutator and XDR Pseudomonas aeruginosa. J. Antimicrob. Chemother. 78, 1785–1794 (2023).
Chan, D. C. K. et al. Nutrient limitation sensitizes Pseudomonas aeruginosa to vancomycin. ACS Infect. Dis. 9, 1408–1423 (2023).
Nordmann, P. et al. Mechanisms of reduced susceptibility to cefiderocol among isolates from the CREDIBLE-CR and APEKS-NP clinical trials. Microb. Drug Resist. 28, 398–407 (2022).
Schick, A. & Kassen, R. Rapid diversification of Pseudomonas aeruginosa in cystic fibrosis lung-like conditions. Proc. Natl Acad. Sci. USA 115, 10714–10719 (2018).
Tingpej, P. et al. Phenotypic characterization of clonal and nonclonal Pseudomonas aeruginosa strains isolated from lungs of adults with cystic fibrosis. J. Clin. Microbiol. 45, 1697–1704 (2007).
Turner, K. H., Wessel, A. K., Palmer, G. C., Murray, J. L. & Whiteley, M. Essential genome of Pseudomonas aeruginosa in cystic fibrosis sputum. Proc. Natl Acad. Sci. USA 112, 4110–4115 (2015).
Tielen, P. et al. Regulatory and metabolic networks for the adaptation of Pseudomonas aeruginosa biofilms to urinary tract-like conditions. PLoS ONE 8, e71845 (2013).
Bedhomme, S. et al. Evolutionary changes after translational challenges imposed by horizontal gene transfer. Genome Biol. Evol. 11, 814–831 (2019).
Poulsen, B. E. et al. Defining the core essential genome of Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 116, 10072–10080 (2019).
Ahmed, M. N. et al. The evolutionary trajectories of P. aeruginosa in biofilm and planktonic growth modes exposed to ciprofloxacin: beyond selection of antibiotic resistance. npj Biofilms Microbiomes 6, 1–10 (2020).
Santos-Lopez, A., Marshall, C. W., Scribner, M. R., Snyder, D. J. & Cooper, V. S. Evolutionary pathways to antibiotic resistance are dependent upon environmental structure and bacterial lifestyle. eLife 8, e47612 (2019).
Azimi, S. et al. Allelic polymorphism shapes community function in evolving Pseudomonas aeruginosa populations. ISME J. 14, 1929–1942 (2020).
Center for Drug Evaluation and Research. Cefiderocol Injection (FDA, 2022).
Morita, Y., Cao, L., Gould, V. C., Avison, M. B. & Poole, K. nalD encodes a second repressor of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa. J. Bacteriol. 188, 8649–8654 (2006).
Vaillancourt, M. et al. A compensatory RNase E variation increases iron piracy and virulence in multidrug-resistant Pseudomonas aeruginosa during Macrophage infection. PLoS Pathog. 19, e1010942 (2023).
Tian, Z.-X., Yi, X.-X., Cho, A., O’Gara, F. & Wang, Y.-P. CpxR activates MexAB-OprM efflux pump expression and enhances antibiotic resistance in both laboratory and clinical nalB-type isolates of Pseudomonas aeruginosa. PLoS Pathog. 12, e1005932 (2016).
Belcher, L. J., Dewar, A. E., Ghoul, M. & West, S. A. Kin selection for cooperation in natural bacterial populations. Proc. Natl Acad. Sci. USA 119, e2119070119 (2022).
Yang, L., Chen, L., Shen, L., Surette, M. & Duan, K. Inactivation of MuxABC-OpmB transporter system in Pseudomonas aeruginosa leads to increased ampicillin and carbenicillin resistance and decreased virulence. J. Microbiol 49, 107–114 (2011).
Nadell, C. D., Drescher, K. & Foster, K. R. Spatial structure, cooperation and competition in biofilms. Nat. Rev. Microbiol. 14, 589–600 (2016).
Amanatidou, E. et al. Biofilms facilitate cheating and social exploitation of β-lactam resistance in Escherichia coli. npj Biofilms Microbiomes 5, 1–10 (2019).
Laborda, P., Martínez, J. L. & Hernando-Amado, S. Evolution of habitat-dependent antibiotic resistance in Pseudomonas aeruginosa. Microbiol. Spectr. 10, e00247–22 (2022).
Scribner, M. R., Santos-Lopez, A., Marshall, C. W., Deitrick, C. & Cooper, V. S. Parallel evolution of tobramycin resistance across species and environments. mBio 11 https://doi.org/10.1128/mbio.00932-20 (2020).
Masi, M., Pinet, E. & Pagès, J.-M. Complex response of the CpxAR two-component system to β-lactams on antibiotic resistance and envelope homeostasis in Enterobacteriaceae. Antimicrob. Agents Chemother. 64, e00291–20 (2020).
Adamiak, J. W. et al. Loss of RND-type multidrug efflux pumps triggers iron starvation and lipid A modifications in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 65, e00592–21 (2021).
Rajput, A. et al. Advanced transcriptomic analysis reveals the role of efflux pumps and media composition in antibiotic responses of Pseudomonas aeruginosa. Nucleic Acids Res. 50, 9675–9688 (2022).
Rumbaugh, K. P. et al. Kin selection, quorum sensing and virulence in pathogenic bacteria. Proc. Biol. Sci. 279, 3584–3588 (2012).
Buckling, A. & Brockhurst, M. A. Kin selection and the evolution of virulence. Heredity 100, 484–488 (2008).
Chen, R., Déziel, E., Groleau, M.-C., Schaefer, A. L. & Greenberg, E. P. Social cheating in a Pseudomonas aeruginosa quorum-sensing variant. Proc. Natl Acad. Sci. USA 116, 7021–7026 (2019).
LaFayette, S. L. et al. Cystic fibrosis-adapted Pseudomonas aeruginosa quorum sensing lasR mutants cause hyperinflammatory responses. Sci. Adv. 1, e1500199 (2015).
Tostado-Islas, O. et al. Iron limitation by transferrin promotes simultaneous cheating of pyoverdine and exoprotease in Pseudomonas aeruginosa. ISME J. 15, 2379–2389 (2021).
Andersen, S. B., Marvig, R. L., Molin, S., Krogh Johansen, H. & Griffin, A. S. Long-term social dynamics drive loss of function in pathogenic bacteria. Proc. Natl Acad. Sci. USA 112, 10756–10761 (2015).
Kim, A. et al. Pharmacodynamic profiling of a siderophore-conjugated monocarbam in Pseudomonas aeruginosa: assessing the risk for resistance and attenuated efficacy. Antimicrob. Agents Chemother. 59, 7743–7752 (2015).
Tomaras, A. P. et al. Adaptation-based resistance to siderophore-conjugated antibacterial agents by Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 57, 4197–4207 (2013).
Wardell, S. J. T. et al. Genome evolution drives transcriptomic and phenotypic adaptation in Pseudomonas aeruginosa during 20 years of infection. Microb. Genomics 7, 000681 (2021).
Nguyen, A. T. et al. Adaptation of iron homeostasis pathways by a Pseudomonas aeruginosa pyoverdine mutant in the cystic fibrosis lung. J. Bacteriol. 196, 2265–2276 (2014).
Murdoch, C. C. & Skaar, E. P. Nutritional immunity: the battle for nutrient metals at the host–pathogen interface. Nat. Rev. Microbiol. 20, 657–670 (2022).
Kang, D. et al. Pyoverdine-dependent virulence of Pseudomonas aeruginosa isolates from cystic fibrosis patients. Front. Microbiol. 10, 2048 (2019).
Kirienko, N. V., Ausubel, F. M. & Ruvkun, G. Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 112, 1821–1826 (2015).
Kirienko, D. R., Kang, D. & Kirienko, N. V. Novel pyoverdine inhibitors mitigate Pseudomonas aeruginosa pathogenesis. Front. Microbiol. 9, 3317 (2019).
Ipe, D. S. & Ulett, G. C. Evaluation of the in vitro growth of urinary tract infection-causing Gram-negative and Gram-positive bacteria in a proposed synthetic human urine (SHU) medium. J. Microbiol. Methods 127, 164–171 (2016).
Held, K., Ramage, E., Jacobs, M., Gallagher, L. & Manoil, C. Sequence-verified two-allele transposon mutant library for Pseudomonas aeruginosa PAO1. J. Bacteriol. 194, 6387–6389 (2012).
Hmelo, L. R. et al. Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange. Nat. Protoc. 10, 1820–1841 (2015).
Spero, M. A. & Newman, D. K. Chlorate specifically targets oxidant-starved, antibiotic-tolerant populations of Pseudomonas aeruginosa biofilms. mBio 9, e01400–e01418 (2018).
Deatherage, D. E. & Barrick, J. E. Identification of mutations in laboratory-evolved microbes from next-generation sequencing data using breseq. Methods Mol. Biol. 1151, 165–188 (2014).
Oksanen, J. et al. Vegan: community ecology package. (CRAN, 2022).
Letunic, I. & Bork, P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. 49, W293–W296 (2021).
CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 30th ed. CLSI supplement M100. (Clinical and Laboratory Standards Institute, 2020).
Choi, K.-H. & Schweizer, H. P. mini-Tn7 insertion in bacteria with single attTn7 sites: example Pseudomonas aeruginosa. Nat. Protoc. 1, 153–161 (2006).
Jorth, P., Spero, M. A., Livingston, J. & Newman, D. K. Quantitative visualization of gene expression in mucoid and nonmucoid Pseudomonas aeruginosa aggregates reveals localized peak expression of alginate in the hypoxic zone. mBio 10, e02622–19 (2019).
Garčic, A. A highly sensitive, simple determination of serum iron using chromazurol B. Clin. Chim. Acta 94, 115–119 (1979).
Acknowledgements
This research was funded by grant numbers JORTH17F5, JORTH19P0 and MILESI21F0 from the Cystic Fibrosis Foundation and grant numbers K22AI127473, R21AI151362 and R01AI14642 from the NIH/National Institute of Allergy and Infectious Diseases and R01Hl136143 from the NIH/National Heart, Lung, and Blood Institute. We thank Applied Genomics, Computation and Translational Core at Cedars-Sinai Medical Center, for helping with whole-genome sequencing and bulk RNA sequencing. We also thank the Pulmonary Translational Research Core team at the University of Pittsburgh for the P. aeruginosa clinical isolates used in this study.
Author information
Authors and Affiliations
Contributions
Conceptualization, A.C.M.G. and P.J.; methodology, A.C.M.G. and P.J.; formal analysis, A.C.M.G., D.C. and P.J.; investigation, A.C.M.G., M.V., D.C., K.H. and P.J.; resources, Y.D., J.S.L. and P.J.; data curation, A.C.M.G., D.C. and P.J.; writing—original draft preparation, A.C.M.G. and P.J.; writing—review and editing, A.C.M.G., M.V., D.C., Y.D., J.S.L. and P.J.; supervision, A.C.M.G. and P.J.; project administration, A.C.M.G. and P.J.; funding acquisition, A.C.M.G., J.S.L. and P.J. All authors have read and agreed to the published version of the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Peer review
Peer review information
Nature Microbiology thanks James Gurney and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Extended data
Extended Data Fig. 1 Time to achieve growth at high cefiderocol concentrations during experimental evolution.
Mean time to achieve growth at (a) 4 μg/ml and (b) 1,024 μg/ml cefiderocol during experimental evolution in cystic fibrosis (SCFM2 planktonic and aggregate populations) and synthetic human urine (SHU) media (Mean ± SD; p-values: one-way ANOVA with Tukey’s multiple comparison test, n = 8 parallel cultures).
Extended Data Fig. 2 Genetic diversity of populations evolved in the presence or absence of increasing concentrations of cefiderocol.
Shannon diversity indices were calculated from SNV frequencies in control populations passaged in cefiderocol-free media and in cefiderocol-evolved populations (mean; p-values, two-sided unpaired t-test, n = 8 parallel cultures).
Extended Data Fig. 3 Maximum parsimony phylogenetic trees of evolved isolates show diversity within each cefiderocol resistant population.
Maximum-likelihood phylogenetic trees were constructed based on mutations detected in cefiderocol evolved isolated colonies (20 colonies per evolved population). Phylogenetic trees were rooted on the PAO1 wild-type genome. Bootstrap values are indicated on respective branches. Trees were plotted using iTOL.
Extended Data Fig. 4 Increased efflux pump gene expression in cpxS variants and decreased antibiotic cross-resistance after drug-free selection.
a, Expression of mexA and muxA genes known to be under the control of the CPX two-component system, by RT-qPCR in PAO1 wild-type and cpxSSNV variants (T163P, S227G, and S235A) (mean ± SEM, ANOVA Dunnett′s multiple comparisons test, n = 6 independent experiments). b, Heatmap of antimicrobial susceptibilities of populations evolved in the absence of cefiderocol for 15 d. Heatmap indicates the mean log2 MIC fold change of drug-free-passaged populations compared to cefiderocol resistant populations (n = 8 populations per growth condition). CFDC, cefiderocol; CAZ, ceftazidime; CEP, cefepime, ATM, aztreonam, TOB, tobramycin, COL, colistin, PMB, polymyxin B, CIP ciprofloxacin.
Extended Data Fig. 5 In vitro competitions between ancestral and cefiderocol-resistant evolved populations.
a, Planktonic competitions between ancestral and cefiderocol-resistant evolved populations in SCFM2 and SHU. b, Biofilm competitions between ancestral and cefiderocol-resistant evolved populations in SCFM2 with (right) or without (left) cefiderocol. Evolved and ancestral populations were tagged with eYFP and mApple fluorescent proteins, respectively. The fluorescent populations were competed (1:1 ratios) in the presence or absence of cefiderocol (64 μg/ml). Planktonic populations growth was determined by monitoring fluorescence over time (h). Experiments were performed in triplicate, in three independent experimental sets (mean ± SD n = 3 independent experiments). Biofilm competitions were visualized by confocal microscopy.
Extended Data Fig. 6 Ancestral populations are unable to grow in the presence of cefiderocol.
Growth in the presence and absence of 64 μg/ml cefiderocol of pre-adapted populations was determined by monitoring fluorescence over time (h). Experiments were performed in triplicate, in three independent experimental sets (mean ± SD n = 3 independent experiments).
Extended Data Fig. 7 Production of pyoverdine and pyochelin and cefiderocol susceptibilities of evolved isolated colonies.
Pyoverdine and pyochelin production by evolved isolated colonies in relation to cefiderocol susceptibility (Two-sided Spearman correlation, n = 160).
Extended Data Fig. 8 Bacterial siderophores confer cefiderocol cross-protection.
a, Ferric iron chelating activity of cefiderocol and bacterial siderophores. The chelating activity was detected by the colorimetric changes of chrome azurol B (OD630nm) at different chelator concentrations (0, 1, 2.5, 5, 10, 25, 50, 100 and 250 µM) (mean ± SEM, ANOVA, n = 2 independent experiments). b, Enterobactin protects K. pneumoniae (Kp), E. coli (Ec), B. cenocepacia (Bc), and B. multivorans (Bm) from cefiderocol killing in a dose-dependent manner. The combinatorial effect of enterobactin with cefiderocol is expressed by the log2 cefiderocol fractional inhibitory concentration (FIC; n = 3 independent experiments, mean ± SD). c, Planktonic competitions between P. aeruginosa (PAO1::mApple or cpxSS227G::mApple) and K. pneumoniae (ATCC 13883::eYFP – left) or E. coli (ATCC 25922::eYFP – right) in the presence of inhibitory concentrations with or without additional pyoverdine (8 µg/ml). The growth of K. pneumoniae and E. coli was measured by eYFP fluorescence area under the curve (AUC) (mean ± SEM, ANOVA, Dunnett′s multiple comparisons test, n = 5 independent experiments). d, Pyoverdine production by P. aeruginosa lab strains and clinical isolates in SCFM2 (mean ± SEM, ANOVA, Tukey′s multiple comparisons test, n = 3 independent experiments).
Supplementary information
Supplementary Table 1
Material list. Supplementary Table 2 SCFM2 and SHU chemical composition. Supplementary Table 3 Primer list. Supplementary Table 4 Complete list of mutated genes detected in PAO1 after 10 days of pre-adaptation to SCFM2 and SHU. Supplementary Table 5 Complete list of mutated genes in the evolved populations with increasing concentrations of cefiderocol. Mutations detected in ancestral and control populations were filtered out. Supplementary Table 6 Complete list of mutated genes detected in isolated colonies from cefiderocol evolved SCFM2-planktonic populations. Supplementary Table 7 Complete list of mutated genes in clinical isolates sequentially recovered from ICU-admitted patients infected with P. aeruginosa. Supplementary Table 8 Complete list of mutated genes evolving in cefiderocol-resistant populations propagated for 14 days in the absence of cefiderocol. Supplementary Table 9 Differentially expressed genes in protective interactions compared with non-protective interactions. Supplementary Table 10 Summary of statistical analyses.
Source data
Source Data Fig. 1
Statistical source data for Fig. 1.
Source Data Fig. 2
Statistical source data for Fig. 2.
Source Data Fig. 3
Statistical source data for Fig. 3.
Source Data Fig. 4
Statistical source data for Fig. 4.
Source Data Fig. 5
Statistical source data for Fig. 5.
Source Data Extended Data Fig. 1
Statistical source data for Extended Data Fig. 1.
Source Data Extended Data Fig. 2
Statistical source data for Extended Data Fig. 2.
Source Data Extended Data Fig. 4
Statistical source data for Extended Data Fig. 4.
Source Data Extended Data Fig. 5
Statistical source data for Extended Data Fig. 5.
Source Data Extended Data Fig. 6
Statistical source data for Extended Data Fig. 6.
Source Data Extended Data Fig. 7
Statistical source data for Extended Data Fig. 7.
Source Data Extended Data Fig. 8
Statistical source data for Extended Data Fig. 8.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Galdino, A.C.M., Vaillancourt, M., Celedonio, D. et al. Siderophores promote cooperative interspecies and intraspecies cross-protection against antibiotics in vitro. Nat Microbiol 9, 631–646 (2024). https://doi.org/10.1038/s41564-024-01601-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41564-024-01601-4
This article is cited by
-
Siderophores mediate antibiotic resistance
Nature Microbiology (2024)