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  • Barceló, Isabel M.Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (författare)

Transferable AmpCs in Klebsiella pneumoniae : interplay with peptidoglycan recycling, mechanisms of hyperproduction, and virulence implications

  • Artikel/kapitelEngelska2024

Förlag, utgivningsår, omfång ...

  • American Society for Microbiology,2024
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:umu-225507
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-225507URI
  • https://doi.org/10.1128/aac.01315-23DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Chromosomal and transferable AmpC β-lactamases represent top resistance mechanisms in different gram-negatives, but knowledge regarding the latter, mostly concerning regulation and virulence-related implications, is far from being complete. To fill this gap, we used Klebsiella pneumoniae (KP) and two different plasmid-encoded AmpCs [DHA-1 (AmpR regulator linked, inducible) and CMY-2 (constitutive)] as models to perform a study in which we show that blockade of peptidoglycan recycling through AmpG permease inactivation abolished DHA-1 inducibility but did not affect CMY-2 production and neither did it alter KP pathogenic behavior. Moreover, whereas regular production of both AmpC-type enzymes did not attenuate KP virulence, when blaDHA-1 was expressed in an ampG-defective mutant, Galleria mellonella killing was significantly (but not drastically) attenuated. Spontaneous DHA-1 hyperproducer mutants were readily obtained in vitro, showing slight or insignificant virulence attenuations together with high-level resistance to β-lactams only mildly affected by basal production (e.g., ceftazidime, ceftolozane/tazobactam). By analyzing diverse DHA-1-harboring clinical KP strains, we demonstrate that the natural selection of these hyperproducers is not exceptional (>10% of the collection), whereas mutational inactivation of the typical AmpC hyperproduction-related gene mpl was the most frequent underlying mechanism. The potential silent dissemination of this kind of strains, for which an important fitness cost-related contention barrier does not seem to exist, is envisaged as a neglected threat for most β-lactams effectiveness, including recently introduced combinations. Analyzing whether this phenomenon is applicable to other transferable β-lactamases and species as well as determining the levels of conferred resistance poses an essential topic to be addressed.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Escobar-Salom, MariaHealth Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (författare)
  • Cabot, GabrielHealth Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (författare)
  • Perelló-Bauzà, PauHealth Research Institute of the Balearic Islands (IdISBa), Palma, Spain (författare)
  • Jordana-Lluch, ElenaHealth Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (författare)
  • Taltavull, BielHealth Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (författare)
  • Torrens, GabrielUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)(Swepub:umu)gato0010 (författare)
  • Rojo-Molinero, EstrellaHealth Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (författare)
  • Zamorano, LauraHealth Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (författare)
  • Pérez, AstridNational Center for Microbiology, Instituto de Salud Carlos III (ISCIII), Madrid, Spain (författare)
  • Oliver, AntonioHealth Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (författare)
  • Juan, CarlosHealth Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (författare)
  • Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, SpainHealth Research Institute of the Balearic Islands (IdISBa), Palma, Spain (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Antimicrobial Agents and Chemotherapy: American Society for Microbiology68:50066-48041098-6596

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