R. Craig MacLean

Fitness costs of antibiotic resistance mutations in rich media do not reliably predict those in infection-like environments

Jack Knowles, Lauren Pittaccio, Selina Lindon, Corey Woods et autres

Abstract The acquisition of antibiotic resistance is typically associated with a fitness cost, reducing the competitive ability of cells in the absence of antibiotics. Our ability to predict these costs informs our ability to predict how likely it is that resistance will …

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Competition constrains parasite adaptation to thermal heterogeneity.

Samuel Te Greenrod, Daniel Cazares, Weronika Ślesak, Tobias E. Hector et autres

under fluctuating temperatures (37°C-42°C) in monoculture and in co-culture. Without competition, fluctuating temperatures resulted in intermediate thermal phenotypes in the phage φ14-1 and, in both phages, resulted in more variable evolutionary outcomes compared to static conditions. Selection from both fluctuating temperatures and …

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Resistance potentiators: Evolutionary catalysts of antibiotic resistance

R. Craig MacLean, Adam Mulkern, Liam P. Shaw

Why do even closely-related bacteria differ in their capacity to evolve antibiotic resistance? Drawing on evidence from experimental evolution, pathogen genomics, and molecular microbiology, this Essay argues that the evolution of antibiotic resistance in bacterial genomes is frequently catalyzed by the presence …

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Beyond resistance and tolerance: rethinking evolutionary responses to antibiotics from the perspective of individual bacterial cells

R. Craig MacLean, Rafael Peña‐Miller

Antibiotic resistance and tolerance are thought to be the key phenotypic traits that underpin evolutionary adaptation to antibiotics. However, the concepts of resistance and tolerance can be traced back to population-level assays developed by Fleming in the 1920s. Recent single-cell studies have …

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Competition constrains parasite adaptation to thermal heterogeneity

Samuel T. E. Greenrod, Daniel Cazares, Weronika A Slesak, Tobias E. Hector et autres

Abstract Temporal thermal heterogeneity is expected to favour intermediate, generalist phenotypes that can maintain growth across a broad thermal range but have sub-optimal growth at any single temperature. Yet, thermal variation typically occurs in the presence of additional selection pressures which may …

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DNA-damaging combination treatments impose genotype-specific constraints on hypermutator evolvability

Adam J. Mulkern, Stefan Oliver Bassler, William Matlock, Athanasios Typas et autres

Abstract Bacterial hypermutator strains drive rapid evolution of antibiotic resistance in chronic infections. Inspired by cancer therapy approaches that exploit synthetic lethality by targeting DNA repair deficiencies in hypermutator tumours, we tested whether pairing a conventional antibiotic with a secondary DNA-damaging agent …

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Conjugation structures plasmid populations through host-lineage restriction

William Matlock, R. Craig MacLean

Abstract Conjugation mediates plasmid transfer between bacterial species, driving the horizontal spread of traits like antibiotic resistance. However, genomic and experimental evidence indicates that many conjugative plasmids are restricted to particular host lineages despite broad theoretical host ranges. Using 4,281 plasmids from …

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Rapid adaptation accelerates competitive suppression in a parasite community

Samuel T. E. Greenrod, Daniel Cazares, Weronika A Slesak, Tobias E. Hector et autres

Environmental stress leads to changes in community composition by altering competitive hierarchies and pushing taxa towards extinction. Parasites and their communities are particularly vulnerable to stress due to environmental sensitivity of infection steps and dependence on host fitness. Parasite populations might avoid …

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First characterization of the marine ecosystem of Archer Fiord in the Lasting Ice Area of the High Arctic: a productivity paradox

Maxime Geoffroy, Audrey Limoges, Mathieu Ardyna, Lisa C. Matthes et autres

The Lasting Ice Area along the northern coastline of Ellesmere Island and Greenland will be the region where Arctic multiyear sea ice will persist the longest in a warming climate, making this area critical for ice-dependent species. In 2019, the Tuvaijuittuq Marine …

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mgrB inactivation confers enhanced pathogenicity and immune evasion over mcr-1 expression in colistin-resistant Klebsiella pneumoniae

Zhuoren Ling, Zheng Ruicheng, Yanjun Dong, Wenjuan Yin et autres

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Trade-offs between phage resistance and conjugative ability shape the ecological and evolutionary response of a multidrug resistance plasmid to plasmid-dependent phage

Daniel Cazares, Eliza Rayner, Adrián Cazares, Wendy Figueroa et autres

Abstract Phage therapy is a promising alternative to antibiotics to treat multidrug resistant infections. Plasmid dependent phages (PDPs) are particularly attractive as therapeutics because they can both kill targeted pathogen cells, whilst also potentially preventing the further spread of antibiotic resistance genes …

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Evolutionary rescue accelerates competitive exclusion in a parasite community

Samuel T. E. Greenrod, Daniel Cazares, Weronika A Slesak, Tobias E. Hector et autres

Abstract Environmental stress drives biodiversity loss by altering competitive hierarchies and pushing taxa towards extinction. Parasites and their communities are particularly vulnerable to stress due to environmental sensitivity of infection steps, variation in species tolerance during co-infections, and dependence on host fitness. …

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