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Transferable AmpCs in Klebsiella pneumoniae : interplay with peptidoglycan recycling, mechanisms of hyperproduction, and virulence implications
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- Barceló, Isabel M. (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, Spain
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- Escobar-Salom, Maria (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, Spain
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- Cabot, Gabriel (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, Spain
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- American Society for Microbiology, 2024
- 2024
- Engelska.
- Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 68:5
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- AmpR regulator
- blaCMY-2
- blaDHA-1
- Galleria mellonella
- Klebsiella pneumoniae
- peptidoglycan recycling
- transferable AmpC β-lactamases
- virulence
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Barceló, Isabel ...
- Escobar-Salom, M ...
- Cabot, Gabriel
- Perelló-Bauzà, P ...
- Jordana-Lluch, E ...
- Taltavull, Biel
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- Torrens, Gabriel
- Rojo-Molinero, E ...
- Zamorano, Laura
- Pérez, Astrid
- Oliver, Antonio
- Juan, Carlos
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