Lee, J. Y., Tsolis, R. M. & Baumler, A. J. The microbiome and gut homeostasis. Science 377, eabp9960 (2022).
Argaw-Denboba, A. et al. Paternal microbiome perturbations impact offspring fitness. Nature 629, 652–659 (2024).
Duran, P. et al. Microbial interkingdom interactions in roots promote Arabidopsis survival. Cell 175, 973–983.e14 (2018).
Wilde, J., Slack, E. & Foster, K. R. Host control of the microbiome: mechanisms, evolution, and disease. Science 385, eadi3338 (2024).
Zhang, J. Y. et al. NRT1.1B is associated with root microbiota composition and nitrogen use in field-grown rice. Nat. Biotechnol. 37, 676–684 (2019).
Cordero, O. X. et al. Ecological populations of bacteria act as socially cohesive units of antibiotic production and resistance. Science 337, 1228–1231 (2012).
Goodrich, J. K., Davenport, E. R., Waters, J. L., Clark, A. G. & Ley, R. E. Cross-species comparisons of host genetic associations with the microbiome. Science 352, 532–535 (2016).
Lyng, M. & Kovacs, A. T. Frenemies of the soil: Bacillus and Pseudomonas interspecies interactions. Trends Microbiol. 31, 845–857 (2023).
Garcia-Bayona, L. & Comstock, L. E. Bacterial antagonism in host-associated microbial communities. Science 361, 1215 (2018).
Kehe, J. et al. Positive interactions are common among culturable bacteria. Sci. Adv. 7, eabi7159 (2021).
Dahlstrom, K. M., McRose, D. L. & Newman, D. K. Keystone metabolites of crop rhizosphere microbiomes. Curr. Biol. 30, R1131–R1137 (2020).
Krespach, M. K. C. et al. Streptomyces polyketides mediate bacteria–fungi interactions across soil environments. Nat. Microbiol. 8, 1348–1361 (2023).
Purtschert-Montenegro, G. et al. Pseudomonas putida mediates bacterial killing, biofilm invasion and biocontrol with a type IVB secretion system. Nat. Microbiol. 7, 1547–1557 (2022).
Barone, G. D. et al. Implications of bacteria–bacteria interactions within the plant microbiota for plant health and productivity. J. Zhejiang Univ. Sci. B 25, 1039–1054 (2024).
Mavrodi, D. V., Blankenfeldt, W. & Thomashow, L. S. Phenazine compounds in fluorescent Pseudomonas spp. biosynthesis and regulation. Annu. Rev. Phytopathol. 44, 417–445 (2006).
Dar, D., Thomashow, L. S., Weller, D. M. & Newman, D. K. Global landscape of phenazine biosynthesis and biodegradation reveals species-specific colonization patterns in agricultural soils and crop microbiomes. Elife 9, e59726 (2020).
Saunders, S. H. et al. Extracellular DNA promotes efficient extracellular electron transfer by pyocyanin in Pseudomonas aeruginosa biofilms. Cell 182, 919–932.e19 (2020).
McRose, D. L. & Newman, D. K. Redox-active antibiotics enhance phosphorus bioavailability. Science 371, 1033–1037 (2021).
McRose, D. L., Li, J. Y. & Newman, D. K. The chemical ecology of coumarins and phenazines affects iron acquisition by Pseudomonads. Proc. Natl Acad. Sci. USA 120, e2217951120 (2023).
Meirelles, L. A. & Newman, D. K. Phenazines and toxoflavin act as interspecies modulators of resilience to diverse antibiotics. Mol. Microbiol. 117, 1384–1404 (2022).
Moura-Alves, P. et al. AhR sensing of bacterial pigments regulates antibacterial defence. Nature 512, 387–392 (2014).
Guo, S. Q. et al. Microbial synthesis of antibacterial phenazine-1,6-dicarboxylic acid and the role of PhzG in Pseudomonas chlororaphis GP72AN. J. Agric. Food Chem. 68, 2373–2380 (2020).
Perry, E. K. & Newman, D. K. Prevalence and correlates of phenazine resistance in culturable bacteria from a dryland wheat field. Appl. Environ. Microbiol. 88, e0232021 (2022).
Kozdrój, J., Trevors, J. T. & van Elsas, J. D. Influence of introduced potential biocontrol agents on maize seedling growth and bacterial community structure in the rhizosphere. Soil Biol. Biochem. 36, 1775–1784 (2004).
Laursen, J. B. & Nielsen, J. Phenazine natural products: biosynthesis, synthetic analogues, and biological activity. Chem. Rev. 104, 1663–1685 (2004).
Chen, Y. et al. Wheat microbiome bacteria can reduce virulence of a plant pathogenic fungus by altering histone acetylation. Nat. Commun. 9, 3429 (2018).
Briard, B. et al. Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines. Sci. Rep. 5, 8820 (2015).
Hotter, V. et al. A polyyne toxin produced by an antagonistic bacterium blinds and lyses a Chlamydomonad alga. Proc. Natl Acad. Sci. USA 118, e2107695118 (2021).
Mavrodi, D. V. et al. Diversity and evolution of the phenazine biosynthesis pathway. Appl. Environ. Microbiol. 76, 866–879 (2010).
Imai, Y. et al. Evybactin is a DNA gyrase inhibitor that selectively kills Mycobacterium tuberculosis. Nat. Chem. Biol. 18, 1236–1244 (2022).
Perry, E. K., Meirelles, L. A. & Newman, D. K. From the soil to the clinic: the impact of microbial secondary metabolites on antibiotic tolerance and resistance. Nat. Rev. Microbiol. 20, 129–142 (2021).
Ran, H. M., Hassett, D. J. & Lau, G. W. Human targets of Pseudomonas aeruginosa pyocyanin. Proc. Natl Acad. Sci. USA 100, 14315–14320 (2003).
Vos, S. M., Tretter, E. M., Schmidt, B. H. & Berger, J. M. All tangled up: how cells direct, manage and exploit topoisomerase function. Nat. Rev. Mol. Cell Biol. 12, 827–841 (2011).
Laponogov, I. et al. Structural basis of gate-DNA breakage and resealing by Type II topoisomerases. PLoS ONE 5, e11338 (2010).
Zhang, G., Wang, C., Sui, Z. H. & Feng, J. Insights into the evolutionary trajectories of fluoroquinolone resistance in Streptococcus pneumoniae. J. Antimicrob. Chemother. 70, 2499–2506 (2015).
Mostertz, J., Scharf, C., Hecker, M. & Homuth, G. Transcriptome and proteome analysis of Bacillus subtilis gene expression in response to superoxide and peroxide stress. Microbiology 150, 497–512 (2004).
Keren, I., Wu, Y., Inocencio, J., Mulcahy, L. R. & Lewis, K. Killing by bactericidal antibiotics does not depend on reactive oxygen species. Science 339, 1213–1216 (2013).
Liu, Y. Y. & Imlay, J. A. Cell death from antibiotics without the involvement of reactive oxygen species. Science 339, 1210–1213 (2013).
Yan, J. J. et al. Advances in phenazines over the past decade: review of their pharmacological activities, mechanisms of action, biosynthetic pathways and synthetic strategies. Mar. Drugs 19, 610 (2021).
Gonçalves, T. & Vasconcelos, U. Colour me blue: the history and the biotechnological potential of pyocyanin. Molecules 26, 927 (2021).
Dey, T. et al. Outcomes of clofazimine for the treatment of drug-resistant tuberculosis: a systematic review and meta-analysis. J. Antimicrob. Chemother. 68, 284–293 (2013).
Appelbaum, P. C. & Hunter, P. A. The fluoroquinolone antibacterials: past, present and future perspectives. Int. J. Antimicrob. Agents 16, 5–15 (2000).
Swanson, K. et al. Generative AI for designing and validating easily synthesizable and structurally novel antibiotics. Nat. Mach. Intell. 6, 338–353 (2024).
Su, P. et al. Microbiome homeostasis on rice leaves is regulated by a precursor molecule of lignin biosynthesis. Nat. Commun. 15, 23 (2024).
Netzker, T., Shepherdson, E. M. F., Zambri, M. P. & Elliot, M. A. Bacterial volatile compounds: functions in communication, cooperation, and competition. Annu. Rev. Microbiol. 74, 409–430 (2020).
He, Y. W. et al. DSF-family quorum sensing signal-mediated intraspecies, interspecies, and inter-kingdom communication. Trends Microbiol. 31, 36–50 (2023).
Molina-Santiago, C. et al. The extracellular matrix protects Bacillus subtilis colonies from Pseudomonas invasion and modulates plant co-colonization. Nat. Commun. 10, 1919 (2019).
Molina-Santiago, C. et al. Chemical interplay and complementary adaptative strategies toggle bacterial antagonism and co-existence. Cell Rep. 36, 109449 (2021).
Korgaonkar, A., Trivedi, U., Rumbaugh, K. P. & Whiteley, M. Community surveillance enhances Pseudomonas aeruginosa virulence during polymicrobial infection. Proc. Natl Acad. Sci. USA 110, 1059–1064 (2013).
Giddens, S. R., Feng, Y. & Mahanty, H. K. Characterization of a novel phenazine antibiotic gene cluster in Erwinia herbicola Eh1087. Mol. Microbiol. 45, 769–Eh1783 (2002).
Pierson, L. S. & Pierson, E. A. Metabolism and function of phenazines in bacteria: impacts on the behavior of bacteria in the environment and biotechnological processes. Appl. Microbiol. Biotechnol. 86, 1659–1670 (2010).
Mentel, M. et al. Of two make one: the biosynthesis of phenazines. ChemBioChem 10, 2295–2304 (2009).
Li, J., Wu, Q. & Zhu, X. Research progress of phenazine-1-carboxylic acid and its analogue. Chin. J. Org. Chem. 39, 2744–2758 (2019).
Madeira, F. et al. The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic Acids Res. 47, W636–W641 (2019).
McDonald, M., Mavrodi, D. V., Thomashow, L. S. & Floss, H. G. Phenazine biosynthesis in Pseudomonas fluorescens branchpoint from the primary shikimate biosynthetic pathway and role of phenazine-1,6-dicarboxylic acid. J. Am. Chem. Soc. 123, 9459–9460 (2001).
Shemesh, M. & Chai, Y. A combination of glycerol and manganese promotes biofilm formation in Bacillus subtilis via histidine kinase KinD signaling. J. Bacteriol. 195, 2747–2754 (2013).
Bolyen, E. et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 37, 852–857 (2019).
Callahan, B. J. et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581–583 (2016).
Quast, C. et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 41, D590–D596 (2013).
Rognes, T., Flouri, T., Nichols, B., Quince, C. & Mahé, F. VSEARCH: a versatile open source tool for metagenomics. PeerJ 4, e2584 (2016).
McMurdie, P. J. & Holmes, S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE 8, e61217 (2013).
Segata, N. et al. Microbial community function and biomarker discovery in the human microbiome. Genome Biol. 12, P47 (2011).
Chen, I. M. A. et al. IMG/M: integrated genome and metagenome comparative data analysis system. Nucleic Acids Res. 45, D507–D516 (2017).
Wood, D. E., Lu, J. & Langmead, B. Improved metagenomic analysis with Kraken 2. Genome Biol. 20, 257 (2019).
Buchfink, B., Xie, C. & Huson, D. H. Fast and sensitive protein alignment using DIAMOND. Nat. Methods 12, 59–60 (2014).
Gryczan, T. J., Contente, S. & Dubnau, D. Characterization of Staphylococcus aureus plasmids introduced by transformation into Bacillus subtilis. J. Bacteriol. 134, 318–329 (1978).
Chai, Y., Chu, F., Kolter, R. & Losick, R. Bistability and biofilm formation in Bacillus subtilis. Mol. Microbiol. 67, 254–263 (2008).
Ben-Yehuda, S., Rudner, D. Z. & Losick, R. RacA, a bacterial protein that anchors chromosomes to the cell poles. Science 299, 532–536 (2003).
Peters, J. M. et al. A comprehensive, CRISPR-based functional analysis of essential genes in bacteria. Cell 165, 1493–1506 (2016).
Methods for Dilution Antimicrobial Susceptibility Test for Bacteria that Grow Aerobically: Approved Standard CLSI Document M07-A9, 19th edn (CLSI, 2012).
Zhou, Y. & Chen, Y. phz+ strains data [DS/OL]. V1. Science Data Bank https://doi.org/10.57760/sciencedb.25989 (2025).
Liu, C. Identifier-of-Phenazine-Producing-Bacteria (IPPB). GitHub https://github.com/xzliu919/Identifier-of-Phenazine-Producing-Bacteria-IPPB- (2025).