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Eli Mehlferber @emehlferber.bsky.social · 21/08/2026

Third, it emphasizes the value of collaboration across chronic lung research, given the shared features between CF disease stages and non-CF bronchiectasis.

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Eli Mehlferber @emehlferber.bsky.social · 21/08/2026

Second, it flags a number of "canon" CF-adapted genes whose importance should perhaps be revisited. Critically, not being common or distinctive within CF infection does not preclude a gene being an important target of intervention.

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Eli Mehlferber @emehlferber.bsky.social · 21/08/2026

Three main conclusions from this. First, robust comparators are essential when defining environment-specific adaptation.

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Eli Mehlferber @emehlferber.bsky.social · 21/08/2026

And for the smaller set of mutations that are enriched in CF, that enrichment is not CF-specific either. They are also broadly enriched across other chronic lung infection contexts, including pediatric CF and non-CF bronchiectasis.

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Eli Mehlferber @emehlferber.bsky.social · 21/08/2026

Our initial observation held up. Most of the "canonical" CF-adaptive genes do not harbor mutations unique to CF, or unique to any other environment. Their mutations are either seen broadly across environments or not enriched anywhere in particular.

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Eli Mehlferber @emehlferber.bsky.social · 21/08/2026

The whole thing was powered by an awesome pipeline Iris wrote to robustly classify mutations in genes across strains. It's up on her GitHub: github.com/GaTechBrownL...

github.com

GitHub - GaTechBrownLab/Mutant-Calling

Contribute to GaTechBrownLab/Mutant-Calling development by creating an account on GitHub.

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Eli Mehlferber @emehlferber.bsky.social · 21/08/2026

So we did a deep dive: identifying the genes most frequently cited as pathoadaptive in the CF research canon, then running a comparative genomics study to identify mutations across P. aeruginosa strains from ALL environments.

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Eli Mehlferber @emehlferber.bsky.social · 21/08/2026

It started with my earlier work www.biorxiv.org/content/10.6.... Looking at the genes most predictive of a strain coming from a CF environment, we were surprised that many of the genes commonly talked about in the CF literature didn't make the list.

biorxiv.org

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 speciali...

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Eli Mehlferber @emehlferber.bsky.social · 20/05/2026

Take home: some ‘generalists’ are a mixture of cryptic specialists, with repeatable genomic and phenotypic structure that standard lineage views miss. Mapping this structure can help flag when ‘ubiquitous’ species hide meaningful heterogeneity, with relevance to managing human infection risk etc.

biorxiv.org

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Eli Mehlferber @emehlferber.bsky.social · 20/05/2026

We also phenotyped a diverse strain panel: key traits cluster more by environment than by relatedness, supporting the idea that ecological context matters.

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Eli Mehlferber @emehlferber.bsky.social · 20/05/2026

Along the way, we identify which genes provide the strongest diagnostic signals for each environment, uncovering some interesting patterns. Notably, many genes and mutations previously associated with CF-specific adaptation appear to be broadly indicative of chronic lung infection more generally.

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Eli Mehlferber @emehlferber.bsky.social · 20/05/2026

But if convergent cryptic specialization is at play, we would expect the model to learn reproducible environment-associated signals, even after accounting for phylogenetic relatedness. And that is what we find.

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Eli Mehlferber @emehlferber.bsky.social · 20/05/2026

To distinguish between these models, we use a machine learning approach: we train models to predict environment of origin from gene variant presence/absence. If P. aeruginosa were a strict generalist, we would not expect consistent, phylogenetically independent environment-specific patterns.

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Eli Mehlferber @emehlferber.bsky.social · 20/05/2026

We test that by comparing two possibilities: “strict” generalism, where strains are broadly equivalent across environments, and convergent cryptic specialization, where repeated environment-linked adaptation is present via convergent gene gain/loss, but not confined to deep lineages.

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Eli Mehlferber @emehlferber.bsky.social · 20/05/2026

But when we look across the phylogeny, we see a picture where every lineage can do everything, exactly what we would expect for a classic generalist. Or is something else going on?

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Eli Mehlferber @emehlferber.bsky.social · 20/05/2026

So we set out to understand how this pernicious bug succeeds across such a wide range of environments. First, we ask whether P. aeruginosa is in evolving towards distinct specializations, where different clades are associated with different environments.

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Eli Mehlferber @emehlferber.bsky.social · 20/05/2026

PA is often described as “ubiquitous,” which raises a basic question for us ecology-minded folks: is it a generalist? Ecology tends to be skeptical of generalism though. A jack of all trades (but master of none) should be outcompeted by local specialists unless it has some tricks up its sleeve.

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Eli Mehlferber @emehlferber.bsky.social · 20/05/2026

We know a lot about how P. aeruginosa (PA) adapts during chronic infection in the lungs of people with cystic fibrosis, but comparatively little about what it’s doing in other human, or even non-human, environments.

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Eli Mehlferber @emehlferber.bsky.social · 20/05/2026

Hey all! Happy to finally join everyone here on Bluesky, and also to share the culmination of my longest-running postdoc project, now on bioRxiv: “Apparent generalism in Pseudomonas aeruginosa is underpinned by convergent cryptic specialization.” www.biorxiv.org/content/10.6...

biorxiv.org

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