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Mehlferber, E. C.

Publications and source records attributed to Mehlferber, E. C..

6 recordsLinked to original sources

Canonical pathoadaptive cystic fibrosis genes in Pseudomonas aeruginosa are not CF-specific

Research on Pseudomonas aeruginosa adaptation in cystic fibrosis (CF) has historically relied on comparing chronic isolates to laboratory reference strains, or evolving reference strains in environments simulating chronic CF. This work has established a small set of genes, including lasR, mucA, and mexZ, as canonical markers of CF patho-adaptation. However, without broad non-CF comparators, it remains unclear how specific these signatures are to CF. We used a structured literature review to define 20 historically emphasized "canonical CF genes", then evaluated their mutational patterns across 4,475 genetically distinct P. aeruginosa genomes from seven defined clinical and environmental contexts. We tested four competing hypotheses: (1) enrichment in adult CF alone, (2) in adult and pediatric CF combined, (3) in chronic lung infections broadly (including non-CF bronchiectasis), or (4) no strong environment-specific enrichment. We found little evidence that canonical gene mutations were specifically enriched in adult CF or CF more broadly. Instead, loss-of-function and individual mutations in genes including mucA, mexB, and mexZ were enriched across chronic lung infections, while most canonical genes (including lasR) showed no strong environment-specific enrichment. These results demonstrate that a canon of genes believed to drive patho-adaptation in CF instead largely reflects the narrow comparative framework of past studies rather than CF-exclusive selection. Our findings emphasize shared evolutionary pressures between CF and non-CF bronchiectasis, highlighting opportunities to exchange research and therapeutic insights across chronic infection clinical contexts.

microbiology↗

Apparent generalism in Pseudomonas aeruginosa is underpinned by Convergent, Cryptic Specialization

Microbes that span environmental reservoirs and diverse human infections are often described as generalists or as ubiquitous, yet ecological theory predicts generalism should be unstable when specialists outperform within any one niche. Here we show that Pseudomonas aeruginosas apparent ecological breadth reflects convergent, cryptic specialism (CCS) - repeatable, environment-linked genomic differentiation that is not confined to deep lineages - rather than strict specialism or generalism. An analysis of 6,627 genomes with source-environment metadata reveals that environments are broadly dispersed across the phylogeny, inconsistent with lineage-locked specialization. Despite this shallow phylogenetic structure, genome content predicted environment-of-isolation across nine genotype-discernible environments, including under cross-validation that blocks phylogenetic relatedness. Interpretable feature profiles recovered both shared and environment-specific signals, including genomic signatures distinguishing distinct chronic and acute human infections. Finally, phenotypes from 47 diverse strains clustered more strongly by environmental source than by phylogenetic relatedness. Together, these results indicate that widely distributed bacterial "generalists" can comprise mixtures of cryptic, convergent specialists. By mapping genotype-defined ecological structure, our approach can identify when apparent generalists harbor hidden structure relevant to infection risk.

microbiology↗

Linking genomic and phenotypic traits to interaction outcomes in a synthetic phyllosphere community

Predicting microbiome function remains challenging as microbial interactions scale from pairwise encounters to emergent community properties. This is particularly true of disease protective microbial consortia, where pathogen invasion has typically been studied either in terms of single biocontrol agents or in terms of microbiome diversity at the full community level, but rarely in between. Focusing on a 16-member synthetic tomato phyllosphere bacterial community, we combined reciprocal spent-media growth assays of over 600 pairwise and community-level combinations with comparative genomics to dissect the ecological and metabolic drivers of community interactions. Across the interaction network, negative interactions dominated, with community-derived spent media consistently exerting stronger inhibitory effects on bacterial growth across the community than any single-species filtrate. While two isolates (Exiguobacterium sibiricum and Bacillus thuringiensis) exhibited strong inhibitory effects in monoculture assays, community spent media analyses revealed that no single strain was responsible for the pathogen-suppressive phenotype observed in community, indicating that protection against Pseudomonas syringae is an emergent property of the particular community composition. Furthermore, using correlations and cross-validated multivariate models, inhibition strengths were poorly predicted by either genomic annotations or phenotypic strategies. Instead, community context strongly constrained environmental modification and buffered strain-specific effects observed in isolation. Together, these results demonstrate that microbial community function cannot easily be inferred from pairwise interactions or individual strain properties alone, and that both direct and indirect interactions shape phyllosphere community structure and function, with emergent properties such as pathogen suppression arising from collective properties rather than the presence/absence or dominance of individual keystone taxa.

ecology↗

Early phyllosphere microbial associations impact plant reproductive success

O_LIThe above-ground plant microbiome (the phyllosphere) is increasingly recognized as an important component of plant health. We hypothesized that phyllosphere interactions may be disrupted in a greenhouse setting, where microbial dispersal is limited, and that adding a microbial amendment might yield important benefits to the host plant. C_LIO_LIUsing a newly developed synthetic phyllosphere microbiome for Tomato, we tested this hypothesis across multiple trials by manipulating microbial colonization of leaves and measuring subsequent plant growth and reproductive success, comparing results from plants grown in both greenhouse and field settings. C_LIO_LIWe confirmed that greenhouse-grown plants have a depauperate phyllosphere microbiome and that the addition of the synthetic microbial community was responsible for a clear and repeatable increase in fruit production in this setting. We further show that this effect is synergistic with the addition of micronutrient-based soil amendments, with important implications for agriculture. C_LIO_LIThese results suggest that greenhouse environments have poor phyllosphere microbiome establishment, with negative impacts on the plant. The results also implicate the phyllosphere microbiome as a key component of plant fitness, emphasizing that these communities have a clear role to play in the ecology and evolution of plant communities. C_LI

plant biology↗

Induction of autotetraploidy and microbiome associations mediate differential responses to pathogens

It has become increasingly clear that the microbiome plays a critical role in shaping the host organisms response to disease. There also exists mounting evidence that an organisms ploidy level is important in their response to pathogens and parasites. However, no study has determined if or how these two factors influence one another. We investigate the effect of whole-genome duplication in Arabidopsis thaliana on their above-ground (phyllosphere) microbiome, and determine the interacting impacts of ploidy and the microbiome on disease outcome. Using seven independently derived synthetic auto-tetraploid Arabidopsis accessions, a synthetic leaf-associated bacterial community, and the model pathogen Pseudomonas syringae pv. Tomato DC3000, we confirm that polyploids are generally more resistant to pathogens, but illustrate that this resistance may be in part due to a decrease in the reliance on beneficial bacteria. Polyploids fare better against the pathogen than diploids regardless of microbial inoculation, while we observed that diploids harboring an intact microbiome have lower pathogen densities than those without. We then use RNA sequencing to show that diploids have many more differentially expressed defense-related genes in the presence of their phyllosphere microbiota, while polyploids exhibit constitutively activated defenses regardless of exposure to the synthetic community. These results imply that whole-genome duplication can disrupt historical host-microbiome associations, and suggest that a potential cause or consequence of disruption is a heightened capacity for pathogen defense that is less impacted by the microbiome.

plant biology↗

Duplication And Sub/Neofunctionalization Of malvolio, An Insect Homolog Of Nramp, In The Subsocial Beetle Nicrophorus vespilloides

Gene duplication has long been thought to play a facilitating role in evolution. With growing numbers of sequenced genomes, increasing numbers of duplicate genes are uncovered with unknown functions. Here we examine malvolio, a gene involved in heavy metal transport but that also affects behavior in honey bees and Drosophila. There is only one copy of malvolio in honey bees and Drosophila despite its different roles. A phylogenetic analysis in insects suggests that malvolio has duplicated multiple times in different orders. To test if the two copies might have different functions, we examined expression levels of malvolio in brain, fat bodies, Malpighian tubules, midgut, ovaries, testes and thoracic musculature in the beetle Nicrophorus vespilloides. We found that mvl1 was expressed in all tissues, with highest expression in fat bodies and relatively lower expression in testes, Malpighian tubules, and brain, and ovaries. Expression of mvl2 differed, with significant expression only seen in brain and midgut. Because malvolio has been implicated in behavior, and these beetles have highly developed parenting behavior, we next examined expression during different behavioral states including virgin, mating, preparing resources for offspring, feeding offspring and post care. We found differing expression patterns for the two copies, with mvl1 increasing in expression during resource preparation and feeding offspring, and mvl2 decreasing in these same states. Given these patterns of expression, we suggest that malvolio in N. vespilloides has experienced sub/neofunctionalization following its duplication, and is evolving differing and tissue-specific roles in behavior and physiology.

evolutionary biology↗