(FBIOyF) Departamento de Bioquímica Clínica

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Examinando (FBIOyF) Departamento de Bioquímica Clínica por Materia "Acinetobacter"

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  • Miniatura
    ÍtemAcceso Abierto
    Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp
    (American Society for Microbiology, 2024-08-20) Wong, Olivia; Mezcord, Vyanka; Lopez, Christina; Traglia, German M.; Pasteran, Fernando; Tuttobene, Marisel Romina; Corso, Alejandra; Tolmasky, Marcelo E.; Bonomo, Robert A.; Ramírez, María Soledad; https://orcid.org/0000-0002-4780-5311; https://orcid.org/0000-0001-5840-5869; https://orcid.org/0000-0003-0234-4643; https://orcid.org/0000-0002-6298-7811; https://orcid.org/0000-0002-3299-894X; https://orcid.org/0000-0002-9904-7890
    Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) Acinetobacter infections. While resistance has already been reported in A. baumannii, combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of A. baumannii and A. lwoffii to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and β-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR Acinetobacter infections.
  • Miniatura
    ÍtemAcceso Abierto
    The H-NS regulator plays a role in the stress induced by carbapenemase expression in acinetobacter baumannii
    (American Society for Microbiology, 2020-08-26) Huang, Fanny; Fitchett, Noelle; Razo Gutiérrez, Chelsea; Le, Casin; Martínez, Jasmine; Ra, Grace; López, Carolina; González, Lisandro Javier; Sieira, Rodrigo; Vila, Alejandro J.; Bonomo, Robert A.; Ramírez, María Soledad; https://orcid.org/0000-0002-9904-7890
    Disruption of the histone-like nucleoid structuring protein (H-NS) was shown to affect the ability of Gram-negative bacteria to regulate genes associated with virulence, persistence, stress response, quorum sensing, biosynthesis pathways, and cell adhesion. Here, we used the expression of metallo--lactamases (MBLs), known to elicit envelope stress by the accumulation of toxic precursors in the periplasm, to interrogate the role of H-NS in Acinetobacter baumannii, together with other stressors. Using a multidrug-resistant A. baumannii strain, we observed that H-NS plays a role in alleviating the stress triggered by MBL toxic precursors and counteracts the effect of DNA-damaging agents, supporting its role in stress response.