Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 29, Number 11—November 2023
Research

Genotypic Evolution of Klebsiella pneumoniae Sequence Type 512 during Ceftazidime/Avibactam, Meropenem/Vaborbactam, and Cefiderocol Treatment, Italy

Gabriele Arcari, Federico Cecilia, Alessandra Oliva, Riccardo Polani, Giammarco Raponi, Federica Sacco, Alice De Francesco, Francesco Pugliese, and Alessandra CarattoliComments to Author 
Author affiliations: Sapienza University of Rome, Rome, Italy (G. Arcari, F. Cecilia, A. Oliva, R. Polani, G. Raponi, A. De Francesco, F. Pugliese, A. Carattoli); Azienda Ospedaliero-Universitaria Policlinico Umberto I, Rome (A. Oliva, G. Raponi, F. Sacco, F. Pugliese)

Main Article

Figure 3

In silico 3-dimensional structure predictions for mutated OmpK36 porin in Klebsiella pneumoniae sequence type 512 strain 0296 in study of K. pneumoniae genotypic evolution during ceftazidime/avibactam, meropenem/vaborbactam, and cefiderocol treatment, Italy. The outer membrane porin OmpK36 from strain 0296 (blue) containing a 26 aa deletion from residue Thr263 through residue Tyr289 was modeled and compared with the model of reference OmpK36 chain B crystal structure from the Protein Data Bank (no. 6RCP; https://www.rcsb.org) (30). Both ribbon cartoon (top) and surface (bottom) models are shown. Structures for strain 0296 were obtained by using Alphafold2 on the European Galaxy server (https://usegalaxy.eu). Spatial arrangements of the porins in lipid bilayers were visualized by using the positioning of proteins in membranes web server in the Orientations of Proteins in Membranes database (31).

Figure 3. In silico 3-dimensional structure predictions for mutated OmpK36 porin in Klebsiella pneumoniae sequence type 512 strain 0296 in study of K. pneumoniae genotypic evolution during ceftazidime/avibactam, meropenem/vaborbactam, and cefiderocol treatment, Italy. The outer membrane porin OmpK36 from strain 0296 (blue) containing a 26 aa deletion from residue Thr263 through residue Tyr289 was modeled and compared with the model of reference OmpK36 chain B crystal structure from the Protein Data Bank (no. 6RCP; https://www.rcsb.org) (30). Both ribbon cartoon (top) and surface (bottom) models are shown. Structures for strain 0296 were obtained by using Alphafold2 on the European Galaxy server (https://usegalaxy.eu). Spatial arrangements of the porins in lipid bilayers were visualized by using the positioning of proteins in membranes web server in the Orientations of Proteins in Membranes database (31).

Main Article

References
  1. Murray  CJL, Ikuta  KS, Sharara  F, Swetschinski  L, Robles Aguilar  G, Gray  A, et al.; Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399:629–55. DOIPubMedGoogle Scholar
  2. Shirley  M. Ceftazidime-avibactam: a review in the treatment of serious gram-negative bacterial infections. Drugs. 2018;78:675–92. DOIPubMedGoogle Scholar
  3. Yahav  D, Giske  CG, Grāmatniece  A, Abodakpi  H, Tam  VH, Leibovici  L. New β-lactam-β-lactamase inhibitor combinations. Clin Microbiol Rev. 2020;34:e00115–20. DOIPubMedGoogle Scholar
  4. El-Lababidi  RM, Rizk  JG. Cefiderocol: a siderophore cephalosporin. Ann Pharmacother. 2020;54:1215–31. DOIPubMedGoogle Scholar
  5. Ito  A, Nishikawa  T, Matsumoto  S, Yoshizawa  H, Sato  T, Nakamura  R, et al. Siderophore cephalosporin cefiderocol utilizes ferric iron transporter systems for antibacterial activity against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2016;60:7396–401. DOIPubMedGoogle Scholar
  6. David  S, Reuter  S, Harris  SR, Glasner  C, Feltwell  T, Argimon  S, et al.; EuSCAPE Working Group; ESGEM Study Group. Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread. Nat Microbiol. 2019;4:1919–29. DOIPubMedGoogle Scholar
  7. Di Pilato  V, Errico  G, Monaco  M, Giani  T, Del Grosso  M, Antonelli  A, et al.; AR-ISS Laboratory Study Group on carbapenemase-producing Klebsiella pneumoniae. The changing epidemiology of carbapenemase-producing Klebsiella pneumoniae in Italy: toward polyclonal evolution with emergence of high-risk lineages. J Antimicrob Chemother. 2021;76:355–61. DOIPubMedGoogle Scholar
  8. Carattoli  A, Arcari  G, Bibbolino  G, Sacco  F, Tomolillo  D, Di Lella  FM, et al. Evolutionary trajectories toward ceftazidime-avibactam resistance in Klebsiella pneumoniae clinical isolates. Antimicrob Agents Chemother. 2021;65:e0057421. DOIPubMedGoogle Scholar
  9. Hobson  CA, Pierrat  G, Tenaillon  O, Bonacorsi  S, Bercot  B, Jaouen  E, et al. Klebsiella pneumoniae carbapenemase variants resistant to ceftazidime-avibactam: an evolutionary overview. Antimicrob Agents Chemother. 2022;66:e0044722. DOIPubMedGoogle Scholar
  10. Karakonstantis  S, Rousaki  M, Kritsotakis  EI. Cefiderocol: systematic review of mechanisms of resistance, heteroresistance and in vivo emergence of resistance. Antibiotics (Basel). 2022;11:723. DOIPubMedGoogle Scholar
  11. McElheny  CL, Fowler  EL, Iovleva  A, Shields  RK, Doi  Y. In vitro evolution of cefiderocol resistance in an NDM-producing Klebsiella pneumoniae due to functional loss of CirA. Microbiol Spectr. 2021;9:e0177921. DOIPubMedGoogle Scholar
  12. Fröhlich  C, Sørum  V, Tokuriki  N, Johnsen  PJ, Samuelsen  Ø. Evolution of β-lactamase-mediated cefiderocol resistance. J Antimicrob Chemother. 2022;77:2429–36. DOIPubMedGoogle Scholar
  13. Lan  P, Lu  Y, Jiang  Y, Wu  X, Yu  Y, Zhou  J. Catecholate siderophore receptor CirA impacts cefiderocol susceptibility in Klebsiella pneumoniae. Int J Antimicrob Agents. 2022;60:106646. DOIPubMedGoogle Scholar
  14. Klein  S, Boutin  S, Kocer  K, Fiedler  MO, Störzinger  D, Weigand  MA, et al. Rapid development of cefiderocol resistance in carbapenem-resistant Enterobacter cloacae during therapy is associated with heterogeneous mutations in the catecholate siderophore receptor cirA. Clin Infect Dis. 2022;74:905–8. DOIPubMedGoogle Scholar
  15. Jousset  AB, Poignon  C, Yilmaz  S, Bleibtreu  A, Emeraud  C, Girlich  D, et al. Rapid selection of a cefiderocol-resistant Escherichia coli producing NDM-5 associated with a single amino acid substitution in the CirA siderophore receptor. J Antimicrob Chemother. 2023;78:1125–7. DOIPubMedGoogle Scholar
  16. Freire  B, Ladra  S, Parama  JR. Memory-efficient assembly using Flye. IEEE/ACM Trans Comput Biol Bioinform. 2022;19:3564–77.
  17. Wick  RR, Judd  LM, Gorrie  CL, Holt  KE. Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads. PLOS Comput Biol. 2017;13:e1005595. DOIPubMedGoogle Scholar
  18. Wick  RR, Schultz  MB, Zobel  J, Holt  KE. Bandage: interactive visualization of de novo genome assemblies. Bioinformatics. 2015;31:3350–2. DOIPubMedGoogle Scholar
  19. Overbeek  R, Olson  R, Pusch  GD, Olsen  GJ, Davis  JJ, Disz  T, et al. The SEED and the Rapid Annotation of microbial genomes using Subsystems Technology (RAST). Nucleic Acids Res. 2014;42(D1):D206–14. DOIPubMedGoogle Scholar
  20. Seemann  T. Prokka: rapid prokaryotic genome annotation. Bioinformatics. 2014;30:2068–9. DOIPubMedGoogle Scholar
  21. Page  AJ, Cummins  CA, Hunt  M, Wong  VK, Reuter  S, Holden  MTG, et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics. 2015;31:3691–3. DOIPubMedGoogle Scholar
  22. Hoang  DT, Chernomor  O, von Haeseler  A, Minh  BQ, Vinh  LS. UFBoot2: improving the ultrafast bootstrap approximation. Mol Biol Evol. 2018;35:518–22. DOIPubMedGoogle Scholar
  23. Minh  BQ, Schmidt  HA, Chernomor  O, Schrempf  D, Woodhams  MD, von Haeseler  A, et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol. 2020;37:1530–4. DOIPubMedGoogle Scholar
  24. Kalyaanamoorthy  S, Minh  BQ, Wong  TKF, von Haeseler  A, Jermiin  LS. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat Methods. 2017;14:587–9. DOIPubMedGoogle Scholar
  25. Argimón  S, Abudahab  K, Goater  RJE, Fedosejev  A, Bhai  J, Glasner  C, et al. Microreact: visualizing and sharing data for genomic epidemiology and phylogeography. Microb Genom. 2016;2:e000093. DOIPubMedGoogle Scholar
  26. Carattoli  A, Zankari  E, García-Fernández  A, Voldby Larsen  M, Lund  O, Villa  L, et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother. 2014;58:3895–903. DOIPubMedGoogle Scholar
  27. Lam  MMC, Wick  RR, Judd  LM, Holt  KE, Wyres  KL. Kaptive 2.0: updated capsule and lipopolysaccharide locus typing for the Klebsiella pneumoniae species complex. Microb Genom. 2022;8:000800. DOIPubMedGoogle Scholar
  28. Lam  MMC, Wick  RR, Watts  SC, Cerdeira  LT, Wyres  KL, Holt  KE. A genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex. Nat Commun. 2021;12:4188. DOIPubMedGoogle Scholar
  29. Pettersen  EF, Goddard  TD, Huang  CC, Meng  EC, Couch  GS, Croll  TI, et al. UCSF ChimeraX: Structure visualization for researchers, educators, and developers. Protein Sci. 2021;30:70–82. DOIPubMedGoogle Scholar
  30. Wong  JLC, Romano  M, Kerry  LE, Kwong  HS, Low  WW, Brett  SJ, et al. OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo. Nat Commun. 2019;10:3957. DOIPubMedGoogle Scholar
  31. Lomize  MA, Lomize  AL, Pogozheva  ID, Mosberg  HI. OPM: orientations of proteins in membranes database. Bioinformatics. 2006;22:623–5. DOIPubMedGoogle Scholar
  32. Jolley  KA, Bray  JE, Maiden  MCJ. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res. 2018;3:124. DOIPubMedGoogle Scholar
  33. Deleo  FR, Chen  L, Porcella  SF, Martens  CA, Kobayashi  SD, Porter  AR, et al. Molecular dissection of the evolution of carbapenem-resistant multilocus sequence type 258 Klebsiella pneumoniae. Proc Natl Acad Sci U S A. 2014;111:4988–93. DOIPubMedGoogle Scholar
  34. García-Fernández  A, Miriagou  V, Papagiannitsis  CC, Giordano  A, Venditti  M, Mancini  C, et al. An ertapenem-resistant extended-spectrum-β-lactamase-producing Klebsiella pneumoniae clone carries a novel OmpK36 porin variant. Antimicrob Agents Chemother. 2010;54:4178–84. DOIPubMedGoogle Scholar
  35. Deguchi  T, Fukuoka  A, Yasuda  M, Nakano  M, Ozeki  S, Kanematsu  E, et al. Alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV in quinolone-resistant clinical isolates of Klebsiella pneumoniae. Antimicrob Agents Chemother. 1997;41:699–701. DOIPubMedGoogle Scholar
  36. Cannatelli  A, Giani  T, D’Andrea  MM, Di Pilato  V, Arena  F, Conte  V, et al.; COLGRIT Study Group. MgrB inactivation is a common mechanism of colistin resistance in KPC-producing Klebsiella pneumoniae of clinical origin. Antimicrob Agents Chemother. 2014;58:5696–703. DOIPubMedGoogle Scholar
  37. Verhamme  DT, Arents  JC, Postma  PW, Crielaard  W, Hellingwerf  KJ. Glucose-6-phosphate-dependent phosphoryl flow through the Uhp two-component regulatory system. Microbiology (Reading). 2001;147:3345–52. DOIPubMedGoogle Scholar
  38. Lam  MMC, Wick  RR, Wyres  KL, Gorrie  CL, Judd  LM, Jenney  AWJ, et al. Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in Klebsiella pneumoniae populations. Microb Genom. 2018;4:e000196. DOIPubMedGoogle Scholar
  39. Shields  RK, Chen  L, Cheng  S, Chavda  KD, Press  EG, Snyder  A, et al. Emergence of ceftazidime-avibactam resistance due to plasmid-borne blaKPC-3 mutations during treatment of carbapenem-resistant Klebsiella pneumoniae infections. Antimicrob Agents Chemother. 2017;61:e02097–16.PubMedGoogle Scholar
  40. Tooke  CL, Hinchliffe  P, Bonomo  RA, Schofield  CJ, Mulholland  AJ, Spencer  J. Natural variants modify Klebsiella pneumoniae carbapenemase (KPC) acyl-enzyme conformational dynamics to extend antibiotic resistance. J Biol Chem. 2021;296:100126. DOIPubMedGoogle Scholar
  41. Villa  L, Feudi  C, Fortini  D, Brisse  S, Passet  V, Bonura  C, et al. Diversity, virulence, and antimicrobial resistance of the KPC-producing Klebsiella pneumoniae ST307 clone. Microb Genom. 2017;3:e000110. DOIPubMedGoogle Scholar
  42. Zhang  Z, Du  W, Wang  M, Li  Y, Su  S, Wu  T, et al. Contribution of the colicin receptor CirA to biofilm formation, antibotic resistance, and pathogenicity of Salmonella Enteritidis. J Basic Microbiol. 2020;60:72–81. DOIPubMedGoogle Scholar
  43. Wyres  KL, Holt  KE. Klebsiella pneumoniae population genomics and antimicrobial-resistant clones. Trends Microbiol. 2016;24:944–56. DOIPubMedGoogle Scholar
  44. Zheng  D, Bergen  PJ, Landersdorfer  CB, Hirsch  EB. Differences in fosfomycin resistance mechanisms between Pseudomonas aeruginosa and Enterobacterales. Antimicrob Agents Chemother. 2022;66:e0144621. DOIPubMedGoogle Scholar
  45. Ortiz-Padilla  M, Portillo-Calderón  I, de Gregorio-Iaria  B, Blázquez  J, Rodríguez-Baño  J, Pascual  A, et al. Interplay among different fosfomycin resistance mechanisms in Klebsiella pneumoniae. Antimicrob Agents Chemother. 2021;65:e01911–20. DOIPubMedGoogle Scholar
  46. Thorpe  HA, Booton  R, Kallonen  T, Gibbon  MJ, Couto  N, Passet  V, et al. A large-scale genomic snapshot of Klebsiella spp. isolates in Northern Italy reveals limited transmission between clinical and non-clinical settings. Nat Microbiol. 2022;7:2054–67. DOIPubMedGoogle Scholar
  47. Arcari  G, Di Lella  FM, Bibbolino  G, Mengoni  F, Beccaccioli  M, Antonelli  G, et al. A multispecies cluster of VIM-1 carbapenemase-producing Enterobacterales linked by a novel, highly conjugative, and broad-host-range IncA plasmid forebodes the reemergence of VIM-1. Antimicrob Agents Chemother. 2020;64:e02435–19. DOIPubMedGoogle Scholar
  48. Liu  J, Wang  R, Fang  M. Clinical and drug resistance characteristics of Providencia stuartii infections in 76 patients. J Int Med Res. 2020;48:300060520962296. DOIPubMedGoogle Scholar
  49. Molnár  S, Flonta  MMM, Almaş  A, Buzea  M, Licker  M, Rus  M, et al. Dissemination of NDM-1 carbapenemase-producer Providencia stuartii strains in Romanian hospitals: a multicentre study. J Hosp Infect. 2019;103:165–9. DOIPubMedGoogle Scholar
  50. Akbiyik  A, Hepçivici  Z, Eşer  I, Uyar  M, Çetin  P. The effect of oropharyngeal aspiration before position change on reducing the incidence of ventilator- associated pneumonia. Eur J Clin Microbiol Infect Dis. 2021;40:615–22. DOIPubMedGoogle Scholar

Main Article

Page created: September 05, 2023
Page updated: November 02, 2023
Page reviewed: November 02, 2023
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external