Elevated mutation rates in multi-azole resistant Aspergillus fumigatus drive rapid evolution of antifungal resistance.

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.

A chromosomal mutation is superior to a plasmid-encoded mutation for plasmid fitness cost compensation.

Plasmids are important vectors of horizontal gene transfer in microbial communities but can impose a burden on the bacteria that carry them. Such plasmid fitness costs are thought to arise principally from conflicts between chromosomal- and plasmid-encoded molecular machineries, and thus can be ameliorated by compensatory mutations (CMs) that reduce or resolve the underlying causes. CMs can arise on plasmids (i.

Co-occurring microflora and mucin drive diversification and pathoadaptation.

While several environmental factors contribute to the evolutionary diversification of the pathogenic bacterium during cystic fibrosis lung infections, relatively little is known about the impact of the surrounding microbiota. By using experimental evolution we show that the presence of , or them both, prevent the evolution of loss of virulence, which repeatedly occurs in the absence of these species due to mutations in regulators of the Quinolone Signal quorum sensing system, and . Moreover, the strength of the effect of co-occurring species is attenuated through changes in the physical environment by the addition of mucin, resulting in selection for phenotypes resembling those evolved in the absence of the co-occurring species.

Aspergillus fumigatus strains that evolve resistance to the agrochemical fungicide ipflufenoquin in vitro are also resistant to olorofim.

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 evolution can disrupt antibiotic exposure protection through competitive exclusion of the protective species.

Antibiotic degrading bacteria can reduce the efficacy of drug treatments by providing antibiotic exposure protection to pathogens. While this has been demonstrated at the ecological timescale, it is unclear how exposure protection might alter and be affected by pathogen antibiotic resistance evolution. Here, we utilised a two-species model cystic fibrosis (CF) community where we evolved the bacterial pathogen Pseudomonas aeruginosa in a range of imipenem concentrations in the absence or presence of Stenotrophomonas maltophilia, which can detoxify the environment by hydrolysing β-lactam antibiotics.

Ecological dynamics of plasmid transfer and persistence in microbial communities.

Plasmids are a major driver of horizontal gene transfer in prokaryotes, allowing the sharing of ecologically important accessory traits between distantly related bacterial taxa. Within microbial communities, interspecies transfer of conjugative plasmids can rapidly drive the generation genomic innovation and diversification. Recent studies are starting to shed light on how the microbial community context, that is, the bacterial diversity together with interspecies interactions that occur within a community, can alter the dynamics of conjugative plasmid transfer and persistence.

Inter-species interactions alter antibiotic efficacy in bacterial communities.

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 quantify, and identify mechanisms for, community-modulated changes of efficacy for clinically relevant antibiotics against the pathogen Pseudomonas aeruginosa in model cystic fibrosis (CF) lung communities derived from clinical samples.

Ecology and evolution of antimicrobial resistance in bacterial communities.

Accumulating evidence suggests that the response of bacteria to antibiotics is significantly affected by the presence of other interacting microbes. These interactions are not typically accounted for when determining pathogen sensitivity to antibiotics. In this perspective, we argue that resistance and evolutionary responses to antibiotic treatments should not be considered only a trait of an individual bacteria species but also an emergent property of the microbial community in which pathogens are embedded.

A Tale of Three Species: Adaptation of Sodalis glossinidius to Tsetse Biology, Metabolism, and Host Diet.

The tsetse fly is the insect vector for the parasite, the causative agent of human African trypanosomiasis. The colonization and spread of the trypanosome correlate positively with the presence of a secondary symbiotic bacterium, The metabolic requirements and interactions of the bacterium with its host are poorly understood, and herein we describe a metabolic model of metabolism. The model enabled the design and experimental verification of a defined medium that supports growth This has been used subsequently to analyze aspects of metabolism, revealing multiple unique adaptations of the symbiont to its environment.

Temporal dynamics of bacteria-plasmid coevolution under antibiotic selection.

Horizontally acquired genes can be costly to express even if they encode useful traits, such as antibiotic resistance. We previously showed that when selected with tetracycline, Escherichia coli carrying the tetracycline-resistance plasmid RK2 evolved mutations on both replicons that together provided increased tetracycline resistance at reduced cost. Here we investigate the temporal dynamics of this intragenomic coevolution.

Membrane Trafficking Modulation during Entamoeba Encystation.

Entamoeba histolytica is an intestinal parasite that infects 50-100 million people and causes up to 55,000 deaths annually. The transmissive form of E. histolytica is the cyst, with a single infected individual passing up to 45 million cysts per day, making cyst production an attractive target for infection control.

Adaptive modulation of antibiotic resistance through intragenomic coevolution.

Bacteria gain antibiotic resistance genes by horizontal acquisition of mobile genetic elements (MGE) from other lineages. Newly acquired MGEs are often poorly adapted causing intragenomic conflicts, resolved by compensatory adaptation of the chromosome, the MGE or reciprocal coadaptation. The footprints of such intragenomic coevolution are present in bacterial genomes, suggesting an important role promoting genomic integration of horizontally acquired genes, but direct experimental evidence of the process is limited.

Selective Conditions for a Multidrug Resistance Plasmid Depend on the Sociality of Antibiotic Resistance.

Multidrug resistance (MDR) plasmids frequently carry antibiotic resistance genes conferring qualitatively different mechanisms of resistance. We show here that the antibiotic concentrations selecting for the RK2 plasmid inEscherichia colidepend upon the sociality of the drug resistance: the selection for selfish drug resistance (efflux pump) occurred at very low drug concentrations, just 1.3% of the MIC of the plasmid-free antibiotic-sensitive strain, whereas selection for cooperative drug resistance (modifying enzyme) occurred at drug concentrations exceeding the MIC of the plasmid-free strain.

Disease epidemiology in arthropods is altered by the presence of nonprotective symbionts.

Inherited microbial symbionts can modulate host susceptibility to natural enemy attack. A wider range of symbionts influence host population demography without altering individual susceptibility, and it has been suggested that these may modify host disease risk through altering the rate of exposure to natural enemies. We present the first test of this thesis, specifically testing whether male-killing symbionts alter the epidemiology of a sexually transmitted infection (STI) carried by its host.