Mechanisms of antibiotic action shape the fitness landscapes of resistance mutations

Hemez, Colin; Clarelli, Fabrizio; Palmer, Adam C.; Chindelevitch, Leonid; Cohen, Ted; Wiesch, Pia Abel zur

doi:10.1101/2020.06.01.127571

Cited by 3 publications

(2 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is widely accepted that plasmid-mediated horizontal gene transfer (HGT) of drug-resistance genes plays a crucial role in promoting the evolution of bacterial drug resistance [51]. Bacteria can acquire antibiotic resistance from plasmids, survive and become dominant strains in a natural selection where antibiotics are present [52,53]. Even though plasmid-carrying usually imposes an adaptation cost on the host bacterium, causing the limitation of its spread, the cost can be mitigated over time by compensating mutations [51,54].…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Characterization of the bla VEB-3 bearing IncC plasmid and bla KPC-2 bearing IncFII plasmid in a type I-E CRISPR-Cas system harboring Klebsiella oxytoca stain

Zhong

Liu

Yuan

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Klebsiella oxytoca has become an important pathogen for opportunistic infections. Plasmid-mediated multidrug-resistant strains pose a significant risk to public health, especially when the strains produce carbapenemase. Here, we report the first detection of a blaKPC-2-IncFII plasmid and a blaVEB-3-IncC plasmid in a clinical multidrug-resistant K. oxytoca strain YL6, which has an entire cluster regularly spaced short palindromic repeat (CRISPR)-Cas immune system. Case presentation and methods: A 46-year-old man was hospitalized with chronic fibrous pneumonia. The K. oxytoca strain YL6 was isolated from his sputum sample. It was resistant to all tested antimicrobials, including almost all β-lactams, cephalosporins, quinolones, and aminoglycosides, except for colistin and tigecycline. To investigate this strain further, we conducted whole-genome sequencing and sequence alignment. Furthermore, the emerging plasmids were compared with similar ones available in the gene bank better to understand the genetic composition and evolution of the plasmids. Results: K. oxytoca strain YL6 belongs to ST27. This stain possesses a chromosome with 6,111,288 bp and two plasmids (An IncFII plasmid pYL6-1 and An IncC plasmid pYL6-2) with 101,530 bp and 145,051 bp, respectively. Genomic comparative analysis revealed that pYL-1 shared 70%~85% query cover and 98.65%-99.85% nucleotide identity with nineteen similar IncFII plasmids, and pYL-2 shared 79%~93% query cover and 99.74%-99.99% nucleotide identity with twenty-one similar IncC plasmids. Both groups of plasmids retained the complete coding region of the tra gene during their evolution. We also observed that the blaKPC-2 gene was located on an ISKpn19-orf1-orf2-Tn3-ISKpn27-blaKPC-2-ISKpn6-orf2-orf1-ISKpn19 structure in the multidrug resistance (MDR) region of pYL-1. Meanwhile, the blaVEB-3 gene in pYL6-2 was situated in an IS26-IS6100-blaVEB-3-transpone-ISAs1-qacEΔ1-sul1-ISCR1 casset. Based on additional data, the YL6 strain appears to possess an intact type I-E CRISPR -Cas immune system, which had been confirmed to inhibit the invasion and existence of the blaKPC-IncF plasmid effectively. The proto-spacers gene in pYL6-1, which are essential for the function of the CRISPR-Cas immune system, was no match to the CRISPR system sequence of K. oxytoca. Conclusions: We first reported a multidrug-resistant K. oxytoca with an intact CRISPR-Cas immune system harbors a blaVEB-3-IncC plasmid and a blaKPC-2-IncFII plasmid. There are no proto-spacer sequences matching the CRISPR system of K. oxytoca on the IncFII plasmid pYL6-1, which is crucial for identifying the foreign gene. It is inferred that the blaKPC-2-IncFII plasmid might escape the host's immune recognition by avoiding its proto-spacer DNA Base sequences complementing the gene arrangements of the strain's CRISPR system. The mutual adaptation between the invasive plasmid and host bacteria is bound to increase bacterial drug resistance further and lead to an antimicrobial public crisis, which calls for considerable attention.

show abstract

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Characterization of the bla VEB-3 bearing IncC plasmid and bla KPC-2 bearing IncFII plasmid in a type I-E CRISPR-Cas system harboring Klebsiella oxytoca stain

Zhong

Liu

Yuan

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…under the effect of treatment), then sometimes referring to them as fitness seascapes, has important consequences for the understanding of adaptation, such as resistance evolution (Lässig et al, 2017; King et al, 2022). For example, Hemez et al (2020) found in a simulation study that the drug mode of action (bacteriostatic vs. bactericidal) was changing the shape of the fitness landscape. In line with this, we have found that both density-affecting and trait-affecting treatment types alter trait adaptation trajectories.…”

Section: Discussionmentioning

confidence: 99%

Promoting extinction or minimizing growth? The impact of treatment on trait trajectories in evolving populations

Raatz

Traulsen

2022

Preprint

View full text Add to dashboard Cite

When cancers or bacterial infections establish, small populations of cells have to free themselves from homoeostatic regulations that prevent their expansion. Trait evolution allows these populations to evade this regulation, escape stochastic extinction and climb up the fitness landscape. In this study, we analyse this complex process and investigate the fate of a cell population that underlies the basic processes of birth, death and mutation. We find that the shape of the fitness landscape dictates a circular adaptation trajectory in trait space. We show that successful adaptation is less likely for parental populations with higher turnover (higher birth and death rates). Including density- or trait-affecting treatment we find that these treatment types change the adaptation dynamics in agreement with geometrically derived hypotheses. Treatment strategies that simultaneously target birth and death rates are most effective, but also increase evolvability. By mapping physiological adaptation pathways and molecular drug mechanisms to traits and treatments with clear eco-evolutionary consequences, we can achieve a much better understanding of the adaptation dynamics and the eco-evolutionary mechanisms at play in the dynamics of cancer and bacterial infections.

show abstract

Competition delays multi-drug resistance evolution during combination therapy

Berríos-Caro

Gifford

Galla

2021

Journal of Theoretical Biology

View full text Add to dashboard Cite

Mechanisms of antibiotic action shape the fitness landscapes of resistance mutations

Cited by 3 publications

References 81 publications

WITHDRAWN: Characterization of the bla VEB-3 bearing IncC plasmid and bla KPC-2 bearing IncFII plasmid in a type I-E CRISPR-Cas system harboring Klebsiella oxytoca stain

WITHDRAWN: Characterization of the bla VEB-3 bearing IncC plasmid and bla KPC-2 bearing IncFII plasmid in a type I-E CRISPR-Cas system harboring Klebsiella oxytoca stain

Promoting extinction or minimizing growth? The impact of treatment on trait trajectories in evolving populations

Competition delays multi-drug resistance evolution during combination therapy

Contact Info

Product

Resources

About