Biology subjects

Irby, I.

Publications and source records attributed to Irby, I..

3 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2026

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↗

bioRxiv2024

Environmental differences impact Acinetobacter baumannii phage isolation and infectivity

With the global rise of antimicrobial resistance, phage therapy is increasingly re-gaining traction as a strategy to treat bacterial infections. For phage therapy to be successful however, we first need to isolate appropriate candidate phages for both clinical and experimental research. Acinetobacter baumannii is an opportunistic pathogen known for its ability to rapidly evolve resistance to antibiotics, making it a prime target for phage therapy. Yet phage isolation is often hampered by A. baumanniis ability to rapidly switch between capsular states. Here, we report the discovery and structural characterisation of a novel lytic phage, Mystique. This phage was initially isolated against the wild-type AB5075: a commonly used clinical model strain against which no phage has previously been readily available for the capsulated form. When screening Mystique on 103 highly diverse isolates of A. baumannii, we found that it has a broad host range, being able to infect 85.4% of all tested strains when tested on bacterial lawns - a host range which expanded to 91.3% when tested in liquid culture. This variation between solid and liquid environments on phage infectivity was also observed for several other phages in our collection that were assumed unable to infect AB5075, and capsule negative mutants that initially seemed completely resistant to Mystique proved susceptible when assayed in liquid. Overall, through the discovery of a novel phage we demonstrate how environmental differences can drastically impact phage infectivity with important consequences for phage isolation and characterisation efforts. Author summaryBacterial infections caused by Acinetobacter baumannii are a major global health concern due to high antibiotic resistance, earning it a critical priority pathogen ranking by the WHO. Phage therapy is resurging as a treatment option, with some success against A. baumannii. However, the wild-type clinical model strain used to assess new therapies lacks an available phage, and isolating phages for A. baumannii is challenging due to its complex capsule. Here, we report the discovery of a novel lytic phage, Mystique, which exhibits a broad host range, infecting 94 out of 103 tested A. baumannii strains. We conducted genomic sequencing and structural analysis to fully characterise Mystique. Additionally, we found that the testing environment significantly impacts results; some phages that do not form plaques on bacterial lawns can still infect and amplify in liquid cultures of the same strain. Moreover, mutants resistant to Mystique based on plaque assays were susceptible in liquid culture assays. This work underscores the necessity of a multifaceted approach for phage isolation and characterisation, as traditional phage assays may not be sufficient for studying bacteria-phage dynamics in certain bacteria such as A. baumannii.

microbiology↗