Publications

The environmental use of azole fungicides has led to selective sweeps across multiple loci in the Aspergillus fumigatus genome causing the rapid global expansion of a genetically distinct cluster of resistant genotypes. Isolates within this cluster are also more likely to be resistant to agricultural antifungals with unrelated modes of action. Here we show that this cluster is not only multi-azole resistant but has increased propensity to develop resistance to next generation antifungals because of variants in the DNA mismatch repair system.

https://doi.org/10.1038/s41467-024-54568-5

Widespread use of azole antifungals in agriculture has been linked to resistance in the pathogenic fungus Aspergillus fumigatus. We show that exposure of A. fumigatus to the agrochemical fungicide, ipflufenoquin, in vitro can select for strains that are resistant to olorofim, a first-in-class clinical antifungal with the same mechanism of action. Resistance is caused by non-synonymous mutations within the target of ipflufenoquin/olorofim activity, dihydroorotate dehydrogenase (DHODH), and these variants have no overt growth defects.

https://doi.org/10.1038/s41564-023-01542-4

While several environmental factors contribute to the evolutionary diversification of the pathogenic bacterium Pseudomonas aeruginosa during cystic fibrosis lung infections, relatively little is known about the impact of the surrounding microbiota. Here we how that variation in mucosal environment and the surrounding polymicrobial environment can determine the evolutionary trajectory of P. aeruginosa, partly explaining its diversification and pathoadaptation from acute to chronic phenotype during cystic fibrosis lung infections.

https://doi.org/10.1093/ismeco/ycae043

The efficacy of antibiotic treatments targeting polymicrobial communities is not well predicted by conventional in vitro susceptibility testing based on determining minimum inhibitory concentration (MIC) in monocultures. One reason for this is that inter-species interactions can alter the community members’ susceptibility to antibiotics. Here we show that exploitation of pre-occurring antimicrobial resistance, and inter-specific competition, can have large impacts on pathogen antibiotic susceptibility, highlighting the importance of microbial ecology for designing successful antibiotic treatments for multispecies communities

https://doi.org/10.1038/s41396-021-01130-6

Perspective exploring how antibiotic resistance is affected by the presence of other interacting microbes. There we outline how interspecies interactions can affect the responses of individual species and communities to antibiotic treatment, and how these responses could affect the strength of selection, potentially changing the trajectory of resistance evolution. 

https://doi.org/10.1038/s41396-020-00832-7

The ability of bacteria to negatively affect neighbors, through explicit toxin delivery systems, provides them with an opportunity to manipulate the composition of growing microbial communities. Contact-dependent inhibition (CDI) systems (a Type Vb secretion system) are a distinct subset of competition systems whose contribution to shaping the development of spatially structured bacterial communities are yet to be fully understood. Here, we show that CDI systems have subtle and system-specific effects at the single-cell level, generating single-cell-wide boundaries between CDI-expressing inhibitor cells and their neighbouring targets. 

https://doi.org/10.1016/j.cub.2019.08.074

Bacteria gain antibiotic resistance genes by horizontal acquisition of mobile genetic elements (MGEs) from other lineages. Newly acquired MGEs are often poorly adapted causing intragenomic conflicts; these are resolved by either compensatory adaptation—of the chromosome or the MGE—or reciprocal coadaptation.  Here we show that intragenomic coevolution between plasmids and chromosomes can create genomes comprising multiple replicons that together provide high-level, low-cost resistance, but the resulting co-dependence may limit the spread of coadapted MGEs to other lineages.

https://doi.org/10.1038/s41559-017-0242-3