1887

Microbial Genomics logo

Volume 9, Issue 8

Genomics of iron uptake Open Access

Abstract

Iron is essential for growth in most bacteria due to its redox activity and its role in essential metabolic reactions; it is a cofactor for many bacterial enzymes. The bacterium is a multidrug-resistant nosocomial pathogen. responds to low iron availability imposed by the host through the exploitation of multiple iron-acquisition strategies, which are likely to deliver iron to the cell under a variety of environmental conditions, including human and animal infection. To date, six different gene clusters for active iron uptake have been described in , encoding protein systems involved in (i) ferrous iron uptake (); (ii) haem uptake ( and ); and (iii) synthesis and transport of the baumannoferrin(s) (), acinetobactin (/) and fimsbactin(s) () siderophores. Here we describe the structure, distribution and phylogeny of iron-uptake gene clusters among >1000 genotypically diverse isolates, showing that , , and / clusters are very prevalent across the dataset, whereas the additional haem-uptake system is only present in a portion of the dataset and the gene cluster is very rare. Since the expression of multiple iron-uptake clusters can be linked to virulence, the presence of the additional haem-uptake system may have contributed to the success of some clones.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Acinetobacter baumannii , haem , iron uptake , phylogeny , sequence type and siderophore
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.001080
2023-08-07
2024-09-19
Loading full text...

Full text loading...

/deliver/fulltext/mgen/9/8/mgen001080.html?itemId=/content/journal/mgen/10.1099/mgen.0.001080&mimeType=html&fmt=ahah

References

  1. Artuso I, Poddar H, Evans BA, Visca P. Genomics of Acinetobacter baumannii iron uptake. Figshare 2023 [View Article]
     [Google Scholar]
  2. Antunes LCS, Visca P, Towner KJ. Acinetobacter baumannii: evolution of a global pathogen. Pathog Dis 2014; 71:292–301 [View Article] [PubMed]
     [Google Scholar]
  3. CDC Antibiotic Resistance Threats in the United States, 2019. Atlanta, GA: U.S. Department of Health and Human Services; 2019 10.15620/cdc:82532
  4. Food and Drug Administration Establishing a list of qualifying pathogens under the food and Drug Administration safety and innovation act. Fed Register 2013; 78:35155–35173
     [Google Scholar]
  5. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 2018; 18:318–327 [View Article] [PubMed]
     [Google Scholar]
  6. Weiner-Lastinger LM, Abner S, Edwards JR, Kallen AJ, Karlsson M et al. Antimicrobial-resistant pathogens associated with adult healthcare-associated infections: summary of data reported to the National Healthcare Safety Network, 2015-2017. Infect Control Hosp Epidemiol 2020; 41:1–18 [View Article] [PubMed]
     [Google Scholar]
  7. Di Popolo A, Giannouli M, Triassi M, Brisse S, Zarrilli R. Molecular epidemiological investigation of multidrug-resistant Acinetobacter baumannii strains in four Mediterranean countries with a multilocus sequence typing scheme. Clin Microbiol Infect 2011; 17:197–201 [View Article] [PubMed]
     [Google Scholar]
  8. Diancourt L, Passet V, Nemec A, Dijkshoorn L, Brisse S. The population structure of Acinetobacter baumannii: expanding multiresistant clones from an ancestral susceptible genetic pool. PLoS One 2010; 5:e10034 [View Article] [PubMed]
     [Google Scholar]
  9. Giannouli M, Antunes LCS, Marchetti V, Triassi M, Visca P et al. Virulence-related traits of epidemic Acinetobacter baumannii strains belonging to the international clonal lineages I-III and to the emerging genotypes ST25 and ST78. BMC Infect Dis 2013; 13:282 [View Article] [PubMed]
     [Google Scholar]
  10. Hamidian M, Nigro SJ. Emergence, molecular mechanisms and global spread of carbapenem-resistant Acinetobacter baumannii. Microb Genom 2019; 5:e000306 [View Article] [PubMed]
     [Google Scholar]
  11. Zarrilli R, Pournaras S, Giannouli M, Tsakris A. Global evolution of multidrug-resistant Acinetobacter baumannii clonal lineages. Int J Antimicrob Agents 2013; 41:11–19 [View Article] [PubMed]
     [Google Scholar]
  12. Carretto E, Barbarini D, Dijkshoorn L, van der Reijden TJK, Brisse S et al. Widespread carbapenem resistant Acinetobacter baumannii clones in Italian hospitals revealed by a multicenter study. Infect Genet Evol 2011; 11:1319–1326 [View Article] [PubMed]
     [Google Scholar]
  13. Karah N, Giske CG, Sundsfjord A, Samuelsen Ø. A diversity of OXA-carbapenemases and class 1 integrons among carbapenem-resistant Acinetobacter baumannii clinical isolates from Sweden belonging to different international clonal lineages. Microb Drug Resist 2011; 17:545–549 [View Article] [PubMed]
     [Google Scholar]
  14. Nowak J, Zander E, Stefanik D, Higgins PG, Roca I et al. High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial. J Antimicrob Chemother 2017; 72:3277–3282 [View Article] [PubMed]
     [Google Scholar]
  15. Qureshi ZA, Hittle LE, O’Hara JA, Rivera JI, Syed A et al. Colistin-resistant Acinetobacter baumannii: beyond carbapenem resistance. Clin Infect Dis 2015; 60:1295–1303 [View Article] [PubMed]
     [Google Scholar]
  16. Harding CM, Hennon SW, Feldman MF. Uncovering the mechanisms of Acinetobacter baumannii virulence. Nat Rev Microbiol 2018; 16:91–102 [View Article] [PubMed]
     [Google Scholar]
  17. Zimbler DL, Penwell WF, Gaddy JA, Menke SM, Tomaras AP et al. Iron acquisition functions expressed by the human pathogen Acinetobacter baumannii. Biometals 2009; 22:23–32 [View Article] [PubMed]
     [Google Scholar]
  18. Sheldon JR, Laakso HA, Heinrichs DE, Kudva IT, Cornick NA. Iron acquisition strategies of bacterial pathogens. Microbiol Spectr 2016; 4:4 [View Article] [PubMed]
     [Google Scholar]
  19. Wandersman C, Delepelaire P. Bacterial iron sources: from siderophores to hemophores. Annu Rev Microbiol 2004; 58:611–647 [View Article] [PubMed]
     [Google Scholar]
  20. Cartron ML, Maddocks S, Gillingham P, Craven CJ, Andrews SC. Feo--transport of ferrous iron into bacteria. Biometals 2006; 19:143–157 [View Article] [PubMed]
     [Google Scholar]
  21. Catel-Ferreira M, Marti S, Guillon L, Jara L, Coadou G et al. The outer membrane porin OmpW of Acinetobacter baumannii is involved in iron uptake and colistin binding. FEBS Lett 2016; 590:224–231 [View Article] [PubMed]
     [Google Scholar]
  22. Eijkelkamp BA, Hassan KA, Paulsen IT, Brown MH. Investigation of the human pathogen Acinetobacter baumannii under iron limiting conditions. BMC Genomics 2011; 12:126 [View Article] [PubMed]
     [Google Scholar]
  23. Álvarez-Fraga L, Vázquez-Ucha JC, Martínez-Guitián M, Vallejo JA, Bou G et al. Pneumonia infection in mice reveals the involvement of the feoA gene in the pathogenesis of Acinetobacter baumannii. Virulence 2018; 9:496–509 [View Article] [PubMed]
     [Google Scholar]
  24. Lau CKY, Krewulak KD, Vogel HJ. Bacterial ferrous iron transport: the Feo system. FEMS Microbiol Rev 2016; 40:273–298 [View Article] [PubMed]
     [Google Scholar]
  25. Wandersman C, Stojiljkovic I. Bacterial heme sources: the role of heme, hemoprotein receptors and hemophores. Curr Opin Microbiol 2000; 3:215–220 [View Article] [PubMed]
     [Google Scholar]
  26. Runci F, Gentile V, Frangipani E, Rampioni G, Leoni L et al. Contribution of active iron uptake to Acinetobacter baumannii pathogenicity. Infect Immun 2019; 87:e00755-18 [View Article] [PubMed]
     [Google Scholar]
  27. Antunes LCS, Imperi F, Towner KJ, Visca P. Genome-assisted identification of putative iron-utilization genes in Acinetobacter baumannii and their distribution among a genotypically diverse collection of clinical isolates. Res Microbiol 2011; 162:279–284 [View Article] [PubMed]
     [Google Scholar]
  28. Mihara K, Tanabe T, Yamakawa Y, Funahashi T, Nakao H et al. Identification and transcriptional organization of a gene cluster involved in biosynthesis and transport of acinetobactin, a siderophore produced by Acinetobacter baumannii ATCC 19606T. Microbiology 2004; 150:2587–2597 [View Article] [PubMed]
     [Google Scholar]
  29. Sheldon JR, Skaar EP, Weiss DS. Acinetobacter baumannii can use multiple siderophores for iron acquisition, but only acinetobactin is required for virulence. PLoS Pathog 2020; 16:e1008995 [View Article] [PubMed]
     [Google Scholar]
  30. Song WY, Kim HJ. Current biochemical understanding regarding the metabolism of acinetobactin, the major siderophore of the human pathogen Acinetobacter baumannii, and outlook for discovery of novel anti-infectious agents based thereon. Nat Prod Rep 2020; 37:477–487 [View Article] [PubMed]
     [Google Scholar]
  31. Penwell WF, Arivett BA, Actis LA. The Acinetobacter baumannii entA gene located outside the acinetobactin cluster is critical for siderophore production, iron acquisition and virulence. PLoS One 2012; 7:e36493 [View Article] [PubMed]
     [Google Scholar]
  32. Dorsey CW, Tomaras AP, Connerly PL, Tolmasky ME, Crosa JH et al. The siderophore-mediated iron acquisition systems of Acinetobacter baumannii ATCC 19606 and Vibrio anguillarum 775 are structurally and functionally related. Microbiology 2004; 150:3657–3667 [View Article] [PubMed]
     [Google Scholar]
  33. Gaddy JA, Arivett BA, McConnell MJ, López-Rojas R, Pachón J et al. Role of acinetobactin-mediated iron acquisition functions in the interaction of Acinetobacter baumannii strain ATCC 19606T with human lung epithelial cells, Galleria mellonella caterpillars, and mice. Infect Immun 2012; 80:1015–1024 [View Article] [PubMed]
     [Google Scholar]
  34. Penwell WF, DeGrace N, Tentarelli S, Gauthier L, Gilbert CM et al. Discovery and characterization of new hydroxamate siderophores, baumannoferrin A and B, produced by Acinetobacter baumannii. ChemBioChem 2015; 16:1896–1904 [View Article] [PubMed]
     [Google Scholar]
  35. Penwell WF, Shapiro AB, Giacobbe RA, Gu R-F, Gao N et al. Molecular mechanisms of sulbactam antibacterial activity and resistance determinants in Acinetobacter baumannii. Antimicrob Agents Chemother 2015; 59:1680–1689 [View Article] [PubMed]
     [Google Scholar]
  36. Proschak A, Lubuta P, Grün P, Löhr F, Wilharm G et al. Structure and biosynthesis of fimsbactins A-F, siderophores from Acinetobacter baumannii and Acinetobacter baylyi. ChemBioChem 2013; 14:633–638 [View Article] [PubMed]
     [Google Scholar]
  37. Hamidian M, Hall RM. Dissemination of novel Tn7 family transposons carrying genes for synthesis and uptake of fimsbactin siderophores among Acinetobacter baumannii isolates. Microb Genom 2021; 7:mgen000548 [View Article] [PubMed]
     [Google Scholar]
  38. Bateman TJ, Shah M, Ho TP, Shin HE, Pan C et al. A slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii. Nat Commun 2021; 12:6270 [View Article] [PubMed]
     [Google Scholar]
  39. Giardina BJ, Shahzad S, Huang W, Wilks A. Heme uptake and utilization by hypervirulent Acinetobacter baumannii LAC-4 is dependent on a canonical heme oxygenase (abHemO). Arch Biochem Biophys 2019; 672:108066 [View Article] [PubMed]
     [Google Scholar]
  40. Holbein BE, Ang MTC, Allan DS, Chen W, Lehmann C. Iron-withdrawing anti-infectives for new host-directed therapies based on iron dependence, the Achilles’ heel of antibiotic-resistant microbes. Environ Chem Lett 2021; 19:2789–2808 [View Article] [PubMed]
     [Google Scholar]
  41. Ong’uti S, Czech M, Robilotti E, Holubar M. Cefiderocol: a new cephalosporin stratagem against multidrug-resistant gram-negative bacteria. Clin Infect Dis 2022; 74:1303–1312 [View Article] [PubMed]
     [Google Scholar]
  42. Zhou Z, Alikhan N-F, Sergeant MJ, Luhmann N, Vaz C et al. GrapeTree: visualization of core genomic relationships among 100,000 bacterial pathogens. Genome Res 2018; 28:1395–1404 [View Article] [PubMed]
     [Google Scholar]
  43. Hamidian M, Wick RR, Hartstein RM, Judd LM, Holt KE et al. Insights from the revised complete genome sequences of Acinetobacter baumannii strains AB307-0294 and ACICU belonging to global clones 1 and 2. Microb Genom 2019; 5:e000298 [View Article] [PubMed]
     [Google Scholar]
  44. Iacono M, Villa L, Fortini D, Bordoni R, Imperi F et al. Whole-genome pyrosequencing of an epidemic multidrug-resistant Acinetobacter baumannii strain belonging to the European clone II group. Antimicrob Agents Chemother 2008; 52:2616–2625 [View Article] [PubMed]
     [Google Scholar]
  45. Smith MG, Gianoulis TA, Pukatzki S, Mekalanos JJ, Ornston LN et al. New insights into Acinetobacter baumannii pathogenesis revealed by high-density pyrosequencing and transposon mutagenesis. Genes Dev 2007; 21:601–614 [View Article] [PubMed]
     [Google Scholar]
  46. Rozewicki J, Li S, Amada KM, Standley DM, Katoh K. MAFFT-DASH: integrated protein sequence and structural alignment. Nucleic Acids Res 2019; 47:W5–W10 [View Article] [PubMed]
     [Google Scholar]
  47. Letunic I, Bork P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 2021; 49:W293–W296 [View Article] [PubMed]
     [Google Scholar]
  48. Bertelli C, Laird MR, Williams KP. Simon Fraser University Research Computing Group Lau BY et al. IslandViewer 4: expanded prediction of genomic islands for larger-scale datasets. Nucleic Acids Res 2017; 45:W30–W35 [View Article] [PubMed]
     [Google Scholar]
  49. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
     [Google Scholar]
  50. Tonkin-Hill G, MacAlasdair N, Ruis C, Weimann A, Horesh G et al. Producing polished prokaryotic pangenomes with the Panaroo pipeline. Genome Biol 2020; 21:180 [View Article] [PubMed]
     [Google Scholar]
  51. Page AJ, Taylor B, Delaney AJ, Soares J, Seemann T et al. SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments. Microb Genom 2016; 2:e000056 [View Article] [PubMed]
     [Google Scholar]
  52. Price MN, Dehal PS, Arkin AP. FastTree: computing large minimum evolution trees with profiles instead of a distance matrix. Mol Biol Evol 2009; 26:1641–1650 [View Article] [PubMed]
     [Google Scholar]
  53. Madeira F, Pearce M, Tivey ARN, Basutkar P, Lee J et al. Search and sequence analysis tools services from EMBL-EBI in 2022. Nucleic Acids Res 2022; 50:W276–W279 [View Article] [PubMed]
     [Google Scholar]
  54. Fournier P-E, Vallenet D, Barbe V, Audic S, Ogata H et al. Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genet 2006; 2:e7 [View Article] [PubMed]
     [Google Scholar]
  55. Camargo CH, Cunha MPV, de Barcellos TAF, Bueno MS, Bertani A de J et al. Genomic and phenotypic characterisation of antimicrobial resistance in carbapenem-resistant Acinetobacter baumannii hyperendemic clones CC1, CC15, CC79 and CC25. Int J Antimicrob Agents 2020; 56:106195 [View Article] [PubMed]
     [Google Scholar]
  56. Ou H-Y, Kuang SN, He X, Molgora BM, Ewing PJ et al. Complete genome sequence of hypervirulent and outbreak-associated Acinetobacter baumannii strain LAC-4: epidemiology, resistance genetic determinants and potential virulence factors. Sci Rep 2015; 5:8643 [View Article] [PubMed]
     [Google Scholar]
  57. de Léséleuc L, Harris G, KuoLee R, Xu HH, Chen W. Serum resistance, gallium nitrate tolerance and extrapulmonary dissemination are linked to heme consumption in a bacteremic strain of Acinetobacter baumannii. Int J Med Microbiol 2014; 304:360–369 [View Article] [PubMed]
     [Google Scholar]
  58. Vallenet D, Nordmann P, Barbe V, Poirel L, Mangenot S et al. Comparative analysis of Acinetobacters: three genomes for three lifestyles. PLoS One 2008; 3:e1805 [View Article] [PubMed]
     [Google Scholar]
  59. Vijayakumar S, Biswas I, Veeraraghavan B. Accurate identification of clinically important Acinetobacter spp.: an update. Future Sci OA 2019; 5:FSO395 [View Article] [PubMed]
     [Google Scholar]
  60. Rooney AP, Dunlap CA, Flor-Weiler LB. Acinetobacter lactucae sp. nov., isolated from iceberg lettuce (Asteraceae: Lactuca sativa). Int J Syst Evol Microbiol 2016; 66:3566–3572 [View Article] [PubMed]
     [Google Scholar]
  61. Sezmis AL, Woods LC, Peleg AY, McDonald MJ. Horizontal gene transfer, fitness costs and mobility shape the spread of antibiotic resistance genes into experimental populations of Acinetobacter baylyi. Mol Biol Evol 2023; 40:msad028 [View Article] [PubMed]
     [Google Scholar]
  62. Cook-Libin S, Sykes EME, Kornelsen V, Kumar A. Iron acquisition mechanisms and their role in the virulence of Acinetobacter baumannii. Infect Immun 2022; 90:e0022322 [View Article] [PubMed]
     [Google Scholar]
  63. Antunes LCS, Imperi F, Carattoli A, Visca P, Adler B. Deciphering the multifactorial nature of Acinetobacter baumannii pathogenicity. PLoS ONE 2011; 6:e22674 [View Article] [PubMed]
     [Google Scholar]
  64. Perraud Q, Cantero P, Roche B, Gasser V, Normant VP et al. Phenotypic adaption of Pseudomonas aeruginosa by hacking siderophores produced by other microorganisms. Mol Cell Proteomics 2020; 19:589–607 [View Article] [PubMed]
     [Google Scholar]
  65. Poole K, McKay GA. Iron acquisition and its control in Pseudomonas aeruginosa: many roads lead to Rome. Front Biosci 2003; 8:d661–d686 [View Article] [PubMed]
     [Google Scholar]
  66. Nwugo CC, Gaddy JA, Zimbler DL, Actis LA. Deciphering the iron response in Acinetobacter baumannii: a proteomics approach. J Proteomics 2011; 74:44–58 [View Article] [PubMed]
     [Google Scholar]
  67. Asrat H, Samaroo-Campbell J, Ata S, Quale J. Contribution of iron-transport systems and β-lactamases to cefiderocol resistance in clinical isolates of Acinetobacter baumannii endemic to New York city. Antimicrob Agents Chemother 2023; 67:e0023423 [View Article] [PubMed]
     [Google Scholar]
  68. Moynié L, Luscher A, Rolo D, Pletzer D, Tortajada A et al. Structure and function of the PiuA and PirA siderophore-drug receptors from Pseudomonas aeruginosa and Acinetobacter baumannii. Antimicrob Agents Chemother 2017; 61:e02531-16 [View Article] [PubMed]
     [Google Scholar]
  69. Antonenka U, Nölting C, Heesemann J, Rakin A. Horizontal transfer of Yersinia high-pathogenicity island by the conjugative RP4 attB target-presenting shuttle plasmid. Mol Microbiol 2005; 57:727–734 [View Article] [PubMed]
     [Google Scholar]
  70. Colonna B, Nicoletti M, Visca P, Casalino M, Valenti P et al. Composite IS1 elements encoding hydroxamate-mediated iron uptake in FIme plasmids from epidemic Salmonella spp. J Bacteriol 1985; 162:307–316 [View Article] [PubMed]
     [Google Scholar]
  71. Izumiya H, Sekizuka T, Nakaya H, Taguchi M, Oguchi A et al. Whole-genome analysis of Salmonella enterica serovar Typhimurium T000240 reveals the acquisition of a genomic island involved in multidrug resistance via IS1 derivatives on the chromosome. Antimicrob Agents Chemother 2011; 55:623–630 [View Article] [PubMed]
     [Google Scholar]
  72. Osorio CR, Rivas AJ, Balado M, Fuentes-Monteverde JC, Rodríguez J et al. A transmissible plasmid-borne pathogenicity island confers piscibactin biosynthesis in the fish pathogen Photobacterium damselae subsp. piscicida. Appl Environ Microbiol 2015; 81:5867–5879 [View Article] [PubMed]
     [Google Scholar]
  73. Warner PJ, Williams PH, Bindereif A, Neilands JB. ColV plasmid-specific aerobactin synthesis by invasive strains of Escherichia coli. Infect Immun 1981; 33:540–545 [View Article] [PubMed]
     [Google Scholar]
  74. Anzaldi LL, Skaar EP. Overcoming the heme paradox: heme toxicity and tolerance in bacterial pathogens. Infect Immun 2010; 78:4977–4989 [View Article] [PubMed]
     [Google Scholar]
  75. Behrens HM, Lowe ED, Gault J, Housden NG, Kaminska R et al. Pyocin S5 import into Pseudomonas aeruginosa reveals a generic mode of bacteriocin transport. mBio 2020; 11:e03230-19 [View Article] [PubMed]
     [Google Scholar]
  76. Bouveret E, Journet L, Walburger A, Cascales E, Bénédetti H et al. Analysis of the Escherichia coli Tol-Pal and TonB systems by periplasmic production of Tol, TonB, colicin, or phage capsid soluble domains. Biochimie 2002; 84:413–421 [View Article] [PubMed]
     [Google Scholar]
  77. Braun V, Patzer SI, Hantke K. Ton-dependent colicins and microcins: modular design and evolution. Biochimie 2002; 84:365–380 [View Article] [PubMed]
     [Google Scholar]
  78. Górska A, Sloderbach A, Marszałł MP. Siderophore-drug complexes: potential medicinal applications of the “Trojan horse” strategy. Trends Pharmacol Sci 2014; 35:442–449 [View Article] [PubMed]
     [Google Scholar]
/content/journal/mgen/10.1099/mgen.0.001080
Loading
Genomics of Acinetobacter baumannii iron uptake
M Gen 9, 001080 (2023); https://doi.org/10.1099/mgen.0.001080
/content/journal/mgen/10.1099/mgen.0.001080
/content/journal/mgen/10.1099/mgen.0.001080
Loading

Data & Media loading...

Supplements

Loading data from figshare Loading data from figshare

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error