{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:15:57Z","timestamp":1793139357866,"version":"4.5.0"},"reference-count":106,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001774","name":"University of Sydney","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Porphyrins are versatile biomolecules central to the synthesis of many essential molecules across all domains of life. Their ability to absorb light, accept electrons and facilitate redox reactions underpins diverse biological roles. Importantly, porphyrin properties can be easily tailored through substitutions of side chains and chelated metals. This adaptability has enabled porphyrins to play critical roles in bacterial environmental adaptations, most notably in enhancing competitive advantage and virulence. The association between porphyrin adaptations and virulence in pathogenic bacteria presents a unique opportunity for the development of next-generation antibacterial strategies and therapeutics. By focusing on virulence and virulence-related systems, these innovative strategies aim to address antimicrobial resistance by reducing the selective pressures that drive its emergence, promote evolutionary pathways that favor non-pathogenic adaptations\u00a0and help to restore the balance of commensal microbiota. This review highlights the recent advances in porphyrin and porphyrin-related antibiotic developments, with emphasis on approaches targeting virulence versus bacterial survival. We further discuss emerging virulence-targeted therapeutics, including artificial intelligence and machine learning for novel target and lead discovery.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1842791","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:23:17Z","timestamp":1783916597000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Porphyrin pathways as targets for combating antimicrobial resistance: virulence and therapeutic opportunities"],"prefix":"10.3389","volume":"16","author":[{"given":"Alysha","family":"Pyne","sequence":"first","affiliation":[{"name":"School of Life and Environmental Sciences, University of Sydney","place":["Sydney, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jameel M.","family":"Abduljalil","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Sciences, University of Sydney","place":["Sydney, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann H.","family":"Kwan","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Sciences, University of Sydney","place":["Sydney, NSW, Australia"]},{"name":"The SydneyNano Institute, University of Sydney","place":["Sydney, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.34133\/csbj.0008","article-title":"Antibacterial drug discovery: Deep learning successes and challenges through the structural biology lens","volume":"35","author":"Abduljalil","year":"2026","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"11267","DOI":"10.3390\/ijms262311267","article-title":"Photodynamic inactivation enhances antibiotic efficacy without affecting drug stability: Insights into photosensitizer-antibiotic combination therapies","volume":"26","author":"Acosta","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B3","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/lsm.22474","article-title":"Antimicrobial blue light inactivation of Pseudomonas aeruginosa by photo-excitation of endogenous porphyrins: In vitro and in vivo studies","volume":"48","author":"Amin","year":"2016","journal-title":"Lasers Surg. Med."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.5c01456","article-title":"Structural design and modification of porphyrin-based nanovesicles for enhanced biomedical functionality","volume":"23","author":"Amirinejad","year":"2026","journal-title":"Mol. Pharm"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.3390\/molecules24132456","article-title":"Application of porphyrins in antibacterial photodynamic therapy","volume":"24","author":"Amos-Tautua","year":"2019","journal-title":"Molecules"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202300366R","article-title":"Bacteroides fragilis expresses three proteins similar to Porphyromonas gingivalis HmuY: Hemophore-like proteins differentially evolved to participate in heme acquisition in oral and gut microbiomes","volume":"37","author":"Antonyuk","year":"2023","journal-title":"FASEB J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"7657","DOI":"10.1128\/aac.01472-15","article-title":"Antimicrobial activity of gallium protoporphyrin IX against Acinetobacter baumannii strains displaying different antibiotic resistance phenotypes","volume":"59","author":"Arivett","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112907","article-title":"Investigating the antibacterial activity of salen\/salophene metal complexes: Induction of ferroptosis as part of the mode of action","volume":"209","author":"Baecker","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00793-19","article-title":"Porphyrin production and regulation in cutaneous Propionibacteria","volume":"5","author":"Barnard","year":"2020","journal-title":"mSphere"},{"key":"B10","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/285017a0","article-title":"Biosynthesis of the pigments of life: Formation of the macrocycle","volume":"285","author":"Battersby","year":"1980","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1099\/mic.0.034405-0","article-title":"The Hem and Has haem uptake systems in Serratia marcescens","volume":"156","author":"Benevides-Matos","year":"2010","journal-title":"Microbiol. (Reading)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2421","DOI":"10.1128\/IAI.01821-06","article-title":"The ChrA-ChrS and HrrA-HrrS signal transduction systems are required for activation of the hmuO promoter and repression of the hemA promoter in Corynebacterium diphtheriae","volume":"75","author":"Bibb","year":"2007","journal-title":"Infect. Immun."},{"key":"B13","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.bbabio.2015.05.007","article-title":"Regulation and function of tetrapyrrole biosynthesis in plants and algae","volume":"1847","author":"Brzezowski","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"B14","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.job.2014.12.003","article-title":"The interplay between iron, haem and manganese in Porphyromonas gingivalis","volume":"57","author":"Butler","year":"2015","journal-title":"J. Oral. Biosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/nrmicro.2017.157","article-title":"The human skin microbiome","volume":"16","author":"Byrd","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"943390","DOI":"10.3389\/fcimb.2023.943390","article-title":"Why is manganese so valuable to bacterial pathogens","volume":"13","author":"Capek","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/s1572-1000(05)00007-4","article-title":"Mechanisms in photodynamic therapy: Part one-photosensitizers, photochemistry and cellular localization","volume":"1","author":"Castano","year":"2004","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"B18","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.apmt.2019.06.010","article-title":"Synthesis and characterization of photoactive porphyrin and poly(2-hydroxyethyl methacrylate) based materials with bactericidal properties","volume":"16","author":"Castro","year":"2019","journal-title":"Appl. Mater. Today"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1039\/d0mt00206b","article-title":"Metallotherapeutics development in the age of iron-clad bacteria","volume":"12","author":"Centola","year":"2020","journal-title":"Metallomics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3390\/ph9010016","article-title":"Activity of gallium meso- and protoporphyrin IX against biofilms of multidrug-resistant Acinetobacter baumannii isolates","volume":"9","author":"Chang","year":"2016","journal-title":"Pharm. (Basel)"},{"key":"B21","doi-asserted-by":"publisher","first-page":"11120","DOI":"10.1021\/acs.chemrev.5c00528","article-title":"Heme in bacterial pathogenesis and as an antimicrobial target","volume":"125","author":"Chen","year":"2025","journal-title":"Chem. Rev."},{"key":"B22","doi-asserted-by":"publisher","first-page":"13057","DOI":"10.1074\/jbc.m808905200","article-title":"Structural insight into the heme-based redox sensing by DosS from Mycobacterium tuberculosis","volume":"284","author":"Cho","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"3408","DOI":"10.1016\/j.jmb.2016.03.018","article-title":"Heme synthesis and acquisition in bacterial pathogens","volume":"428","author":"Choby","year":"2016","journal-title":"J. Mol. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"8272","DOI":"10.1038\/s41598-024-55931-8","article-title":"Identification of small molecules affecting the interaction between human hemoglobin and Staphylococcus aureus IsdB hemophore","volume":"14","author":"Cozzi","year":"2024","journal-title":"Sci. Rep."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/frhem.2024.1305741","article-title":"De novo drug design through artificial intelligence: An introduction","volume":"3","author":"Crucitti","year":"2024","journal-title":"Front. Hematol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.00048-16","article-title":"Prokaryotic heme biosynthesis: Multiple pathways to a common essential product","volume":"81","author":"Dailey","year":"2017","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1073\/pnas.1416285112","article-title":"Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin","volume":"112","author":"Dailey","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4534","article-title":"Active site architecture of coproporphyrin ferrochelatase with its physiological substrate coproporphyrin III: Propionate interactions and porphyrin core deformation","volume":"32","author":"Dali","year":"2023","journal-title":"Protein Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2771","DOI":"10.1074\/jbc.ra118.006185","article-title":"Post-transcriptional regulation of the Pseudomonas aeruginosa heme assimilation system (Has) fine-tunes extracellular heme sensing","volume":"294","author":"Dent","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.msec.2019.04.029","article-title":"Porphyrin-silver nanoparticles hybrids: Synthesis, characterization and antibacterial activity","volume":"102","author":"Elashnikov","year":"2019","journal-title":"Mater. Sci. Eng. C. Mater. Biol. Appl."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1080\/17512433.2016.1189325","article-title":"Role of old antimicrobial agents in the management of urinary tract infection","volume":"9","author":"El Sakka","year":"2016","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1039\/c7mt00042a","article-title":"Inhibiting the BfrB : Bfd interaction in Pseudomonas aeruginosa causes irreversible iron accumulation in bacterioferritin and iron deficiency in the bacterial cytosol","volume":"9","author":"Eshelman","year":"2017","journal-title":"Metallomics"},{"key":"B33","doi-asserted-by":"publisher","first-page":"8168","DOI":"10.1021\/acs.jcim.5c01017","article-title":"DGMM: A deep learning-genetic algorithm framework for efficient lead optimization in drug discovery","volume":"65","author":"Fang","year":"2025","journal-title":"J. Chem. Inf. Model."},{"key":"B34","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s40168-023-01461-w","article-title":"Over supplementation with vitamin B12 alters microbe-host interactions in the gut leading to accelerated Citrobacter rodentium colonization and pathogenesis in mice","volume":"11","author":"Forgie","year":"2023","journal-title":"Microbiome"},{"key":"B35","doi-asserted-by":"publisher","first-page":"6066","DOI":"10.1038\/s41467-025-60612-9","article-title":"Inhibiting heme piracy by pathogenic Escherichia coli using de novo-designed proteins","volume":"16","author":"Fox","year":"2025","journal-title":"Nat. Commun."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1016\/j.str.2025.08.007","article-title":"Code to complex: AI-driven de novo binder design","volume":"33","author":"Fox","year":"2025","journal-title":"Structure"},{"key":"B37","doi-asserted-by":"publisher","first-page":"3804","DOI":"10.1021\/jm0700969","article-title":"Inhibition of the bacterial heme oxygenases from Pseudomonas aeruginosa and Neisseria meningitidis: Novel antimicrobial targets","volume":"50","author":"Furci","year":"2007","journal-title":"J. Med. Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"4097","DOI":"10.1038\/s41467-018-06470-0","article-title":"Structural properties of a haemophore facilitate targeted elimination of the pathogen Porphyromonas gingivalis","volume":"9","author":"Gao","year":"2018","journal-title":"Nat. Commun."},{"key":"B39","doi-asserted-by":"publisher","first-page":"40028","DOI":"10.1074\/jbc.m110.163535","article-title":"Characterization of a hemophore-like protein from Porphyromonas gingivalis","volume":"285","author":"Gao","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aat7520","article-title":"Gallium disrupts bacterial iron metabolism and has therapeutic effects in mice and humans with lung infections","volume":"10","author":"Goss","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/s42256-025-00993-0","article-title":"Benchmarking AI-powered docking methods from the perspective of virtual screening","volume":"7","author":"Gu","year":"2025","journal-title":"Nat. Mach. Intell."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.2308.07413","article-title":"Benchmarking generated poses: How rational is structure-based drug design with generative models","author":"Harris","year":"2023","journal-title":"ArXiv"},{"key":"B43","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1128\/AAC.00553-09","article-title":"Structure of the heme biosynthetic Pseudomonas aeruginosa porphobilinogen synthase in complex with the antibiotic alaremycin","volume":"54","author":"Heinemann","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"B44","doi-asserted-by":"publisher","first-page":"6929","DOI":"10.1021\/acs.jmedchem.6b00757","article-title":"Iminoguanidines as allosteric inhibitors of the iron-regulated heme oxygenase (HemO) of Pseudomonas aeruginosa","volume":"59","author":"Heinzl","year":"2016","journal-title":"J. Med. Chem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1111\/bcp.12356","article-title":"Targeting virulence not viability in the search for future antibacterials","volume":"79","author":"Heras","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00012","article-title":"Gallium-protoporphyrin IX inhibits Pseudomonas aeruginosa growth by targeting cytochromes","volume":"7","author":"Hijazi","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1021\/jm301819k","article-title":"Small molecule antivirulents targeting the iron-regulated heme oxygenase (HemO) of P. aeruginosa","volume":"56","author":"Hom","year":"2013","journal-title":"J. Med. Chem."},{"key":"B48","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1021\/acscentsci.0c01621","article-title":"Broad spectrum antibiotic xanthocillin X effectively kills Acinetobacter baumannii via dysregulation of heme biosynthesis","volume":"7","author":"Hubner","year":"2021","journal-title":"ACS Cent. Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.1016\/s0021-9258(18)52279-1","article-title":"Two glutamyl-tRNA reductase activities in Escherichia coli","volume":"266","author":"Jahn","year":"1991","journal-title":"J. Biol. Chem."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2021.148472","article-title":"Naturally zinc-containing bacteriochlorophyll a ([Zn]-BChl a) protects the photosynthetic apparatus of Acidiphilium rubrum from copper toxicity damage","volume":"1862","author":"Jaime-Perez","year":"2021","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"B51","doi-asserted-by":"publisher","first-page":"20313","DOI":"10.1074\/jbc.m110.212605","article-title":"A BchD (magnesium chelatase) mutant of rhodobacter sphaeroides synthesizes zinc bacteriochlorophyll through novel zinc-containing intermediates","volume":"286","author":"Jaschke","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1128\/jb.174.3.1072-1075.1992","article-title":"Enzymatic basis of thiol-stimulated secretion of porphyrins by Escherichia coli","volume":"174","author":"Javor","year":"1992","journal-title":"J. Bacteriol."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2026.150397","article-title":"Post-modified biosynthesis strategy to achieve a heme-mimicking bacterial cellulose hydrogel with synergistic antibacterial functions for infected skin defect therapy","volume":"344","author":"Jiang","year":"2026","journal-title":"Int. J. Biol. Macromol."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00023-15","article-title":"Strain-level differences in porphyrin production and regulation in Propionibacterium acnes elucidate disease associations","volume":"1","author":"Johnson","year":"2016","journal-title":"mSphere"},{"key":"B55","doi-asserted-by":"publisher","first-page":"319","DOI":"10.2217\/fmb-2019-0279","article-title":"In vitro detection of porphyrin-producing wound bacteria with real-time fluorescence imaging","volume":"15","author":"Jones","year":"2020","journal-title":"Future Microbiol."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02555-20","article-title":"A small-molecule modulator of metal homeostasis in Gram-positive pathogens","volume":"11","author":"Juttukonda","year":"2020","journal-title":"mBio"},{"key":"B57","doi-asserted-by":"publisher","first-page":"293ra103","DOI":"10.1126\/scitranslmed.aab2009","article-title":"Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis","volume":"7","author":"Kang","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3390\/polym17233190","article-title":"Recent advances in pharmaceutical and medical applications in the area of selected porphyrinoids connected with PLGA or PLGA-based modalities","volume":"17","author":"Koza","year":"2025","journal-title":"Polymers (Basel)"},{"key":"B59","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1007\/s12275-018-7515-7","article-title":"Fluorescence change of Fusobacterium nucleatum due to Porphyromonas gingivalis","volume":"56","author":"Lee","year":"2018","journal-title":"J. Microbiol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1016\/j.bmcl.2018.02.027","article-title":"Structure-based design and biological evaluation of inhibitors of the pseudomonas aeruginosa heme oxygenase (pa-HemO)","volume":"28","author":"Liang","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B61","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/nyas.14930","article-title":"Antibiotic discovery in the artificial intelligence era","volume":"1519","author":"Lluka","year":"2023","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B62","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1111\/mmi.13041","article-title":"Staphylococcus aureus haem biosynthesis: characterisation of the enzymes involved in final steps of the pathway","volume":"97","author":"Lobo","year":"2015","journal-title":"Mol. Microbiol."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioflm.2022.100095","article-title":"Protoporphyrin IX derived from dual-species anaerobic biofilms of Fusobacterium necrophorum and Porphyromonas levii attenuates bovine neutrophil function","volume":"4","author":"Lockhart","year":"2022","journal-title":"Biofilm"},{"key":"B64","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1111\/mmi.12967","article-title":"The induction of two biosynthetic enzymes helps Escherichia coli sustain heme synthesis and activate catalase during hydrogen peroxide stress","volume":"96","author":"Mancini","year":"2015","journal-title":"Mol. Microbiol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/j.1574-6968.2011.02357.x","article-title":"In vitro activity of deferoxamine against Porphyromonas gingivalis","volume":"323","author":"Moon","year":"2011","journal-title":"FEMS Microbiol. Lett."},{"key":"B66","doi-asserted-by":"publisher","first-page":"20503","DOI":"10.1074\/jbc.M116.728527","article-title":"Metabolite-driven regulation of heme uptake by the Biliverdin IXbeta\/delta-selective heme oxygenase (HemO) of Pseudomonas aeruginosa","volume":"291","author":"Mourino","year":"2016","journal-title":"J. Biol. Chem."},{"key":"B67","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/s0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"B68","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/nature10823","article-title":"Structural basis for iron piracy by pathogenic Neisseria","volume":"483","author":"Noinaj","year":"2012","journal-title":"Nature"},{"key":"B69","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1021\/acsbiomedchemau.5c00045","article-title":"Biosynthetic pathways of alaremycin and its derivative: inhibitors of porphobilinogen synthase in porphyrin biosynthesis from Streptomyces sp. A012304","volume":"5","author":"Okui","year":"2025","journal-title":"ACS Bio Med. Chem. Au"},{"key":"B70","doi-asserted-by":"publisher","first-page":"4629","DOI":"10.1111\/1462-2920.14773","article-title":"Pseudomonas aeruginosa possesses three distinct systems for sensing and using the host molecule haem","volume":"21","author":"Otero-Asman","year":"2019","journal-title":"Environ. Microbiol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"7352","DOI":"10.1021\/acs.jcim.5c00641","article-title":"Generative deep learning for de novo drug design horizontal line a chemical space odyssey","volume":"65","author":"Ozcelik","year":"2025","journal-title":"J. Chem. Inf. Model."},{"key":"B72","doi-asserted-by":"publisher","first-page":"17644","DOI":"10.48550\/arXiv.2205.07249","article-title":"Pocket2Mol: efficient molecular sampling based on 3D protein pockets","volume":"162","author":"Peng","year":"2022","journal-title":"Proc. Mach. Learn. Res."},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-026-00942-8","article-title":"Colouring dysbiosis: FetB-dependent Mn-PPIX produced by Porphyromonas gingivalis shapes the oral microbiota","volume":"12","author":"Phonok","year":"2026","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B74","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1179\/2047773215y.0000000030","article-title":"Antimicrobial resistance: a global multifaceted phenomenon","volume":"109","author":"Prestinaci","year":"2015","journal-title":"Pathog. Glob. Health"},{"key":"B75","doi-asserted-by":"publisher","first-page":"8171","DOI":"10.1021\/jacs.9b00394","article-title":"Small molecule inhibitors of the BfrB-Bfd interaction decrease Pseudomonas aeruginosa fitness and potentiate fluoroquinolone activity","volume":"141","author":"Punchi Hewage","year":"2019","journal-title":"J. Am. Chem. Soc"},{"key":"B76","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.actbio.2022.11.039","article-title":"Light-triggered theranostic hydrogels for real-time imaging and on-demand photodynamic therapy of skin abscesses","volume":"155","author":"Ran","year":"2023","journal-title":"Acta Biomater."},{"key":"B77","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1089\/fpd.2022.0075","article-title":"Antibacterial mechanism of 2R,3R-dihydromyricetin against Staphylococcus aureus: deciphering inhibitory effect on biofilm and virulence based on transcriptomic and proteomic analyses","volume":"20","author":"Ran","year":"2023","journal-title":"Foodborne Pathog. Dis."},{"key":"B78","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.3390\/antibiotics11081105","article-title":"Chelation in antibacterial drugs: from nitroxoline to cefiderocol and beyond","volume":"11","author":"Repac Antic","year":"2022","journal-title":"Antibiotics (Basel)"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007479","article-title":"To B12 or not to B12: Five questions on the role of cobalamin in host-microbial interactions","volume":"15","author":"Rowley","year":"2019","journal-title":"PloS Pathog."},{"key":"B80","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/s43588-024-00737-x","article-title":"Structure-based drug design with equivariant diffusion models","volume":"4","author":"Schneuing","year":"2024","journal-title":"Nat. Comput. Sci."},{"key":"B81","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s00343-012-1075-1","article-title":"Chemical profile of the secondary metabolites produced by a deep-sea sediment-derived fungus Penicillium commune SD-118","volume":"30","author":"Shang","year":"2012","journal-title":"Chin. J. Oceanol. Limnol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1128\/9781555819286.ch3","article-title":"Iron acquisition strategies of bacterial pathogens","author":"Sheldon","year":"2016","journal-title":"Virulence Mech. Bacterial Pathog"},{"key":"B83","doi-asserted-by":"publisher","first-page":"2858","DOI":"10.1039\/d5sc06481c","article-title":"Unlocking the application potential of AlphaFold3-like approaches in virtual screening","volume":"17","author":"Shen","year":"2026","journal-title":"Chem. Sci."},{"key":"B84","doi-asserted-by":"publisher","first-page":"5624","DOI":"10.1039\/c9cs00268e","article-title":"Heme: emergent roles of heme in signal transduction, functional regulation and as catalytic centres","volume":"48","author":"Shimizu","year":"2019","journal-title":"Chem. Soc Rev."},{"key":"B85","doi-asserted-by":"publisher","first-page":"2862","DOI":"10.1002\/anie.201307889","article-title":"Inhibition of heme uptake in Pseudomonas aeruginosa by its hemophore (HasA(p)) bound to synthetic metal complexes","volume":"53","author":"Shirataki","year":"2014","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"B86","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1128\/JB.188.3.1071-1080.2006","article-title":"Bacillus anthracis IsdG, a heme-degrading monooxygenase","volume":"188","author":"Skaar","year":"2006","journal-title":"J. Bacteriol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1021\/acsinfecdis.9b00398","article-title":"Inhibiting iron mobilization from bacterioferritin in Pseudomonas aeruginosa impairs biofilm formation irrespective of environmental iron availability","volume":"6","author":"Soldano","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102575","article-title":"Porphyrins produced by acneic Cutibacterium acnes strains activate the inflammasome by inducing K(+) leakage","volume":"24","author":"Spittaels","year":"2021","journal-title":"iScience"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2026.109558","article-title":"NIR-triggered synergistic photothermal therapy and type I photodynamic therapy using supramolecular porphyrin-phthalocyanine assemblies for the treatment of multidrug-resistant bacterial infections","volume":"171","author":"Su","year":"2026","journal-title":"Bioorg. Chem."},{"key":"B90","doi-asserted-by":"publisher","first-page":"3049","DOI":"10.1016\/j.apsb.2022.02.002","article-title":"Why 90% of clinical drug development fails and how to improve it","volume":"12","author":"Sun","year":"2022","journal-title":"Acta Pharm. Sin. B."},{"key":"B91","doi-asserted-by":"publisher","first-page":"E6652","DOI":"10.1073\/pnas.1700469114","article-title":"Antibacterial photosensitization through activation of coproporphyrinogen oxidase","volume":"114","author":"Surdel","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B92","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1146\/annurev.arplant.57.032905.105448","article-title":"Tetrapyrrole biosynthesis in higher plants","volume":"58","author":"Tanaka","year":"2007","journal-title":"Annu. Rev. Plant Biol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"607","DOI":"10.2217\/fmb.13.30","article-title":"Genetic diversity in the oral pathogen Porphyromonas gingivalis: molecular mechanisms and biological consequences","volume":"8","author":"Tribble","year":"2013","journal-title":"Future Microbiol."},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104927","article-title":"Targeting hemoglobin receptors IsdH and IsdB of Staphylococcus aureus with a single VHH antibody inhibits bacterial growth","volume":"299","author":"Valenciano-Bellido","year":"2023","journal-title":"J. Biol. Chem."},{"key":"B95","doi-asserted-by":"publisher","first-page":"2907","DOI":"10.1128\/jb.179.9.2907-2914.1997","article-title":"Regulation of heme biosynthesis in Salmonella typhimurium: activity of glutamyl-tRNA reductase (HemA) is greatly elevated during heme limitation by a mechanism which increases abundance of the protein","volume":"179","author":"Wang","year":"1997","journal-title":"J. Bacteriol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"2916","DOI":"10.1093\/jac\/dky255","article-title":"Review of the pharmacokinetic properties of nitrofurantoin and nitroxoline","volume":"73","author":"Wijma","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000419","article-title":"Unique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis","volume":"5","author":"Wojtowicz","year":"2009","journal-title":"PloS Pathog."},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01286-14","article-title":"Propionibacterium-produced coproporphyrin III induces Staphylococcus aureus aggregation and biofilm formation","volume":"5","author":"Wollenberg","year":"2014","journal-title":"mBio"},{"key":"B99","doi-asserted-by":"publisher","first-page":"10172","DOI":"10.1038\/ncomms10172","article-title":"Structural analysis of haemoglobin binding by HpuA from the Neisseriaceae family","volume":"6","author":"Wong","year":"2015","journal-title":"Nat. Commun."},{"key":"B100","volume-title":"Antimicrobial resistance: global report on surveillance. Antimicrobial resistance division (AMR), global antimicrobial resistance surveillance system (GLASS)","year":"2014"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202102015","article-title":"Pillar[5]arene-based acid-triggered supramolecular porphyrin photosensitizer for combating bacterial infections and biofilm dispersion","volume":"11","author":"Xia","year":"2022","journal-title":"Adv. Healthc Mater."},{"key":"B102","doi-asserted-by":"publisher","first-page":"2165001","DOI":"10.1080\/20002297.2023.2165001","article-title":"Porphyromonas gingivalis diffusible signaling molecules enhance Fusobacterium nucleatum biofilm formation via gene expression modulation","volume":"15","author":"Yamaguchi-Kuroda","year":"2023","journal-title":"J. Oral. Microbiol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"bbaf533","DOI":"10.1093\/bib\/bbaf533","article-title":"Computational toxicology in drug discovery: Applications of artificial intelligence in ADMET and toxicity prediction","volume":"26","author":"Zhang","year":"2025","journal-title":"Brief Bioinform."},{"key":"B104","doi-asserted-by":"publisher","first-page":"31357","DOI":"10.1021\/jacs.4c11686","article-title":"Deep lead optimization: Leveraging generative AI for structural modification","volume":"146","author":"Zhang","year":"2024","journal-title":"J. Am. Chem. Soc"},{"key":"B105","doi-asserted-by":"publisher","first-page":"3086","DOI":"10.1021\/jacs.5c15876","article-title":"MetalloDock: Decoding metalloprotein-ligand interactions via physics-aware deep learning for metalloprotein drug discovery","volume":"148","author":"Zhang","year":"2026","journal-title":"J. Am. Chem. Soc"},{"key":"B106","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1093\/infdis\/jit842","article-title":"Antimicrobial blue light therapy for multidrug-resistant Acinetobacter baumannii infection in a mouse burn model: Implications for prophylaxis and treatment of combat-related wound infections","volume":"209","author":"Zhang","year":"2014","journal-title":"J. Infect. Dis."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1842791\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:23:19Z","timestamp":1783916599000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1842791\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":106,"alternative-id":["10.3389\/fcimb.2026.1842791"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1842791","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]},"article-number":"1842791"}}