Biology subjects

Mauritzen, J. J.

Publications and source records attributed to Mauritzen, J. J..

4 recordsLinked to original sources

bioRxiv2026

Slow to Start, Free at Last: Dual Effects of Mucin on Escherichia coli Phage T4

Bacteriophages traversing the gastrointestinal tract are exposed to extreme physicochemical stresses that may rapidly compromise virion integrity and shape infection dynamics. While some phages bind to host-derived mucins at mucosal surfaces, the functional consequences of soluble mucin glycans for phage-host interactions remain incompletely understood. Here, we show that soluble mucin glycans exert dual effects on the Escherichia coli phage T4 by delaying infection initiation while simultaneously providing environmental virion stability. Mucin-coated T4 exhibits a lag in the onset of productive infection, consistent with transient steric occlusion from E. coli, yet without impairing overall phage progeny production once infection was established. We further show that E. coli can metabolize purified mucin, supporting a model in which dynamic remodeling of the mucin matrix gradually releases T4 and enables infection. Importantly, mucin coating substantially increases T4 survival under gastrointestinal-like stresses, including acidic pH and protease exposure. Moreover, we find that in a murine gut colonization model, a single oral dose of mucin-coated T4 displayed enhanced fecal persistence over a two-week period, which correlated with prolonged suppression of E. coli populations and delayed resolution of phage-associated functional shifts in the gut microbiome. Together, we find that that soluble mucin glycans actively shape T4 phage infection kinetics, virion stability, and ecological impact in the murine gut, and support mucin-based formulations as a strategy to extend the persistence and efficacy of orally delivered phages.

microbiology↗

bioRxiv2026

Anti-Quorum Sensing Phages Disarm Pseudomonas aeruginosa

By 2050, the death toll from previously preventable or easily curable bacterial infections is projected to surpass that caused by cancer, unless we prevent the spread of antibiotic resistance and develop new therapies. A promising approach is phage therapy, which exploits bacteriophages, natural predators of bacteria. However, bacteria fight back, which can limit its efficacy. Notably, many bacteria rely on cell-cell communication, known as quorum sensing, to orchestrate both virulence programs and phage defenses. To circumvent these, we have engineered anti-quorum sensing phages against the human pathogen Pseudomonas aeruginosa. Our engineered phages effectively degrade quorum-sensing molecules, reduce virulence factor production, and double the survival of P. aeruginosa-infected Galleria mellonella larvae. Moreover, we demonstrate that the anti-quorum sensing phages inhibit quorum sensing in mixed populations of phage-susceptible and phage-resistant cells, demonstrating the ability of the phages to disarm subpopulations phage-resistant P. aeruginosa, which often are selected for during phage treatment. Together, our findings highlight the future therapeutic promise of anti-quorum sensing phages as a dual-action strategy in killing susceptible cells while attenuating virulence across the bacterial population. This approach has the potential to enhance the robustness of phage therapy.

microbiology↗

bioRxiv2025

Overlooked signals: Highly stable quorum sensing molecule in phage lysates induces quorum sensing response

Phage-bacterial interaction studies routinely apply phage lysates at final concentrations of up to 10% of the culture. Consequently, bacterial metabolites such as quorum sensing (QS) signaling molecules are transferred along with the phage lysate to recipient bacterial cells. Here, we show that the Pseudomonas aeruginosa QS molecules 3OC12-HSL and C4-HSL are rapidly degraded in phage lysates. In contrast, the hydrophobic QS molecule PQS is remarkably stable, for at least one year, due to its binding within outer membrane vesicles. Strikingly, we find that PQS exceeds concentrations of 10 {micro}M in standard phage lysate preparations. We show that PQS carried over from phage lysates induces QS-controlled production of the virulence factor pyocyanin in P. aeruginosa. This PQS carryover does not oppose previous conclusions of phage infection-induced PQS production, as we show here, that this response is also triggered by PQS-free phage lysates. Since other bacterial species, including Paracoccus and Vibrio harveyi, also produce hydrophobic QS molecules that are bound within outer membrane vesicles, it is likely that phage lysates from these bacteria may similarly contain stable QS molecules. Collectively, we demonstrate that membrane-bound QS molecules may significantly confound QS-related physiological outcomes of phage-host interaction studies. This can be avoided by using QS synthase mutants for phage propagation or by purifying phage particles from lysates to eliminate QS molecule carryover.

microbiology↗

bioRxiv2025

Persisters are primed for CRISPR-Cas adaptation

In the evolutionary battle between bacteria and mobile genetic elements, such as bacteriophage viruses and plasmids, bacteria have developed intricate defense systems. Among these, the CRISPR-Cas system has been extensively studied and harnessed as a revolutionary gene editing tool. However, while the biochemical process by which this microbial immune system acquires genetic CRISPR memory and immunity against invaders has been comprehensively examined, fundamental questions about the bacterial physiological state underlying how and when CRISPR memory is formed have only been partially explored. Naive CRISPR adaptation is generally rare, but occurs more frequently when bacteria are challenged with replication-deficient phages. In such scenarios, bacteria are not under immediate threat and have ample time to adapt to the phage DNA, without risking cell death. Accordingly, slow growth caused by low temperatures, low aeration, or bacteriostatic antibiotics promotes CRISPR adaptation, possibly by allowing the Cas complexes more time to adapt before being outpaced. Persister cells are dormant antibiotic-tolerant subpopulations of cells with limited metabolic activity. When a mobile genetic element invades a persister cell, its replication is halted until the host cell resumes growth, providing an ideal opportunity for CRISPR adaptation. Here, we show that transiently dormant Escherichia coli persister cells acquire CRISPR immunity 10-fold more frequently than the general bacterial population. Thus, persister cells, in addition to being notoriously antibiotic tolerant, are primed for CRISPR-Cas adaptation and may be in a state of heightened immune capacity and evolution, securing the survival of the population.

microbiology↗