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Exploiting the fitness cost of metallo-β-lactamase expression can overcome antibiotic resistance in bacterial pathogens.
Nat Microbiol
January 2025
Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
Carbapenems are last-resort antibiotics for treating bacterial infections. The widespread acquisition of metallo-β-lactamases, such as VIM-2, contributes to the emergence of carbapenem-resistant pathogens, and currently, no metallo-β-lactamase inhibitors are available in the clinic. Here we show that bacteria expressing VIM-2 have impaired growth in zinc-deprived environments, including human serum and murine infection models.
View Article and Find Full Text PDFNeutral drift upon threshold-like selection promotes variation in antibiotic resistance phenotype.
Nat Commun
December 2024
Michael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, BC, Canada.
Heritable phenotypic variation plays a central role in evolution by conferring rapid adaptive capacity to populations. Mechanisms that can explain genetic diversity by describing connections between genotype and organismal fitness have been described. However, the difficulty of acquiring comprehensive data on genotype-phenotype-environment relationships has hindered the efforts to explain how the ubiquitously observed phenotypic variation in populations emerges and is maintained.
View Article and Find Full Text PDFSynergistic effects of colistin-rifampin-based triple antimicrobial combination therapy against Carbapenem-resistant Pseudomonas aeruginosa: a time-kill assay.
J Antimicrob Chemother
December 2024
Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea.
Background: Our research aimed to investigate the potential of in vitro triple antimicrobial synergism against carbapenem-resistant Pseudomonas aeruginosa (CRPA) as a strategy to overcome antimicrobial resistance.
Methods: We used 12 CRPA blood isolates stocked in the Asian Bacterial Bank between 2016 and 2018. All isolates were tested by multi-locus sequencing and carbapenemase multiplex PCR.
In-vitro activity of the novel β-lactam/β-lactamase inhibitor combinations and cefiderocol against carbapenem-resistant Pseudomonas spp. clinical isolates collected in Switzerland in 2022.
Eur J Clin Microbiol Infect Dis
December 2024
Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science and Medicine, University of Fribourg, Chemin du Musée 18, Fribourg, CH-1700, Switzerland.
To evaluate the in-vitro activity of the novel commercially-available drugs, including meropenem-vaborbactam (MEV), ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), imipenem-relebactam (IPR) as well as cefiderocol (FDC), against carbapenem-resistant Pseudomonas spp. (CRP) isolates. All CRP isolates collected at the Swiss National Reference Laboratory (NARA) over the year 2022 (n = 170) have been included.
View Article and Find Full Text PDFGenomic Epidemiology of Pseudomonas aeruginosa Sequence Type 111.
Eur J Clin Microbiol Infect Dis
December 2024
Cummings School of Medicine, University of Calgary, #9, 3535 Research Road NW, Calgary, AB, Canada.
Article Synopsis
- Pseudomonas aeruginosa ST111 is a global multidrug-resistant strain causing bloodstream infections, and there's limited understanding of its molecular epidemiology in Canada.
- Researchers characterized Canadian ST111 strains collected between 2010-2018 using whole genome sequencing and studied their global evolutionary relationships.
- The study identified three main clades (A, B, C) and two subclades (C1, C2), revealing that clade C2 dominates globally and that serotype switching and genetic element acquisition are significant factors in its evolution.
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