Biology subjects

Qaderi, I.

Publications and source records attributed to Qaderi, I..

3 recordsLinked to original sources

bioRxiv2026

Identification and characterization of new P. aeruginosa phages using a surface receptor platform

Bacteriophages are of increasing interest for their potential use as alternatives to antibiotics for treating drug-resistant infections. Phage steering, specifically receptor-based steering, involves use of phages that bias the development of resistance in bacteria towards phenotypes such as reduced fitness. Phage therapy typically involves administering cocktails of phages with different targets to reduce the likelihood of resistance emerging. To ensure effective steering and cocktail design, there is a need to identify the receptors used by phages of interest, and to isolate phages that use diverse receptors. Here we describe a SURFAce Receptor (SURFAR) platform consisting of a set of defined Pseudomonas aeruginosa strains and mutants for rapid characterization of phage receptors. This platform can also be used to enrich for and isolate diverse phages from environmental samples, yielding novel phage genomes from wastewater. Using the SURFAR platform, two new phages were isolated and characterized: Dalewood, which targets both flagella and the conserved LPS outer core, and Bowman, a biofilm targeting phage capable of supressing growth of a subset of carbapenem-resistant clinical isolates. This tool helps to standardize the laborious but important task of phage receptor characterization, with the goal of expanding the known repertoire of P. aeruginosa phage receptors and phages.

microbiology↗

bioRxiv2026

Structural diversification of phage tail fibres enables recognition of diverse type IV pili

Viruses must recognize receptors on host surfaces to initiate infection, but these receptors can evolve rapidly, posing a fundamental challenge to viral persistence. The type IV pilus of Pseudomonas aeruginosa is an ideal model system to study virus-receptor coevolution because its major pilin subunit PilA exhibits extensive sequence and chemical diversity while remaining essential for phage attachment. Here, we combined large-scale comparative genomics with structural and functional analyses to determine how pilus-dependent phages maintain infectivity despite extensive receptor diversification. Pilin variation was concentrated at solvent-exposed regions, altering filament surface chemistry while preserving key subunit-subunit interfaces. Despite this variation, phages recognized divergent pilins more effectively than polyclonal antisera. However, phages differed markedly in their sensitivity to receptor perturbation: some required electrostatic and structural compatibility, whereas others tolerated substantial receptor modification, including the presence of post-translational glycosylation. Comparisons of AlphaFold3 structural models revealed two distinct tail fibre architectures associated with those phenotypes. Phages encoding tail fibres with conserved receptor-binding domains were more sensitive to receptor perturbation within a given pilin background, while those with structurally diversified binding regions infected strains expressing highly divergent pilins. Together, these findings suggest that modular diversification of receptor-binding proteins provides a structural route by which phages accommodate receptor evolution. SIGNIFICANCEUnderstanding the determinants of viral host range is essential for explaining how viruses persist in the face of receptor diversification. Using pilus-dependent bacteriophages that bind diverse type IV pilins in Pseudomonas aeruginosa, we show that differences in tail fibre architecture are associated with distinct sensitivities to receptor variation. Phages with structurally conserved receptor-binding regions are sensitive to receptor perturbation, whereas those with diversified binding architectures remain infectious across strains expressing highly divergent pilins. Our results identify a structural correlate of receptor recognition breadth and reveal how receptor-binding protein architecture contributes to viral host range and adaptation. These data can inform the selection or engineering of broad-host range phages for therapeutic applications.

microbiology↗

bioRxiv2023

Nutrient Limitation Sensitizes Pseudomonas aeruginosa to Vancomycin

Traditional antibacterial screens rely on growing bacteria in nutrient-replete conditions which are not representative of the natural environment or sites of infection. Instead, screening in more physiologically relevant conditions may reveal novel activity for existing antibiotics. Here, we screened a panel of antibiotics reported to lack activity against the opportunistic Gram-negative bacterium, Pseudomonas aeruginosa, under low-nutrient conditions, and discovered that the glycopeptide vancomycin inhibited growth of P. aeruginosa at low micromolar concentrations through its canonical mechanism of action, disruption of peptidoglycan cross-linking. Spontaneous vancomycin-resistant mutants had activating mutations in the sensor kinase of the two-component CpxSR system, which induced cross-resistance to almost all classes of y-lactams, including the siderophore antibiotic cefiderocol. Other mutations that conferred vancomycin resistance mapped to WapR, an -1,3-rhamnosyltransferase involved in lipopolysaccharide core biosynthesis. A WapR P164T mutant had a modified LPS profile compared to wild type that was accompanied by increased susceptibility to select bacteriophages. We conclude that screening in nutrient-limited conditions can reveal novel activity for existing antibiotics and lead to discovery of new and impactful resistance mechanisms. For Table of Contents Use Only O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/536232v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1119ebeorg.highwire.dtl.DTLVardef@1ccd6c0org.highwire.dtl.DTLVardef@126f3deorg.highwire.dtl.DTLVardef@54a9c0_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗