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PubMed2026

Small serine recombinases are markers for antiphage defense system discovery.

Renewed interest in phage therapy has highlighted a need to understand how bacteria subvert phage infection through antiphage defense systems. Traditionally, strategies to identify antiphage defense systems lack throughput or have limitations for bacterial species where antiphage defense systems are understudied. Herein, we developed a bioinformatic pipeline that uses a small serine recombinase to identify known and unknown antiphage defense systems. Using this approach to query reference genomes and metagenomes, we show that small serine recombinase genes are genetically linked to antiphage defense systems and serve as bait for finding these systems across diverse bacterial phyla. Using co-transcription predictions and statistical analysis of protein domain abundances, we experimentally validated our bioinformatic approach by discovering that KAP P-loop NTPases are fused to putative antiphage domains and reinforce prokaryotic Schlafen proteins as a new class of antiphage defense. Our work shows that small serine recombinases are a reliable genetic marker for the discovery of antiphage defenses across diverse bacterial phyla.

Bacteriophages↗
PubMed2025

Characterization of the novel Cutibacterium acnes phage KIT08 and its associated pseudolysogenic bacterial isolate.

Cutibacterium acnes, formerly Propionibacterium acnes, is a Gram-positive bacterium commonly recognized as an important factor in acne vulgaris and infections associated with prosthetic medical devices. With the rise in antibiotic resistance, phage therapy has gained renewed attention as a promising alternative to antibiotics. In addition to a strict lytic cycle, some virulent phages may enter a pseudolysogenic state and exclude superinfections, thereby significantly limiting the applicability of these potential antimicrobial agents. However, the trade-off induced by phage infection of bacterial cells during this state and its molecular mechanism are yet to be confirmed, especially for C. acnes phages. In this study, a novel Cutibacterium acnes phage, KIT08, was isolated and characterized. It demonstrated rapid infectivity and moderately strong bacteriolysis. After infection of C. acnes NBRC 107,605, pseudolysogenic bacteria were collected and examined for physiological tradeoffs. The pseudolysogenic isolate exhibited slower growth and downregulation of the transcriptional levels of biofilm-producing genes, such as lipase 2 and hyaluronate lyase, leading to a decrease in biofilm formation. Additionally, a genomic study of phage KIT08 revealed that open reading frames 23 and 34 encode putative proteins homologous to repressor C and LTP proteins, which may play an important role in the induction of pseudolysogeny and superinfection exclusion in C. acnes.

Propionibacterium acnes↗
PubMedDate not supplied

[Bacteriophage therapy of septic complications of orthopaedic surgery (author's transl].

Seven septic cases have been treated by bacteriophage; two infections after insertion of a hip prosthesis, two septic arthritis of the knee, one osteomyelitis of the tibia, one septic non-union of the femur and one septic complication following Harrington rodding. Only specific phages were used in association with several types of surgical procedure. The technique of treatment is described. All cases were long-term infections with resistant organisms. Results were good in five, fair in one and one case was a failure. It is concluded that phage therapy may be helpful in the treatment of long-term infections.

Adult↗
PubMed2025

A comprehensive reference catalog of human skin DNA virome reveals novel viral diversity and microenvironmental influences.

UNLABELLED: Human skin serves as a dynamic habitat for a diverse microbiome, including a complex array of viruses whose diversity and roles are not fully understood. A total of 2,760 skin metagenomes from 6 published skin studies were collected. A skin virome catalog was constructed using standard methods in the viromics field. Viral characteristics were identified through cross-cohort meta-analysis and used to characterize viral features across different skin environments. We identified 20,927 viral sequences, which clustered into 2,873 viral operational taxonomic units (vOTUs), uncovering a substantial breadth of viral diversity on human skin. The results also highlight significant differences in viral communities that are associated with varying skin microenvironments. The oily skin is enriched in Papillomaviridae, the dry skin area is enriched in Autographiviridae and Inoviridae, and the moist skin is enriched in Herelleviridae. We also investigated the relationship between bacteriophages and bacteria on the skin surface. We found that skin bacteria such as Pseudomonas, Klebsiella, and Staphylococcus are predicted to be infected by phages from the class Caudoviricetes. This comprehensive skin DNA viral catalog significantly advances our understanding of the virome's role within the skin ecosystem. IMPORTANCE: This study presents a comprehensive reference catalog of the human skin DNA virome, constructed from 2,760 metagenomic datasets collected globally. It identified 20,927 viral sequences, with 90.85% representing previously unknown viruses, greatly expanding our understanding of skin viral diversity. The findings reveal significant differences in viral communities between distinct skin microenvironments (oily, dry, and moist) and highlight close interactions between bacteriophages and their bacterial hosts, suggesting a potential role for the virome in maintaining microbial balance and skin health. This extensive skin viral catalog constitutes a crucial resource for future epidemiological and therapeutic research, potentially facilitating the development of novel phage therapies and diagnostic markers for skin disorders.

Humans↗
PubMed2026

Insights into Genome Ejection by a Therapeutic phiKMV-like Bacteriophage.

Ar-KM is a phiKMV-like therapeutic bacteriophage used in clinical candidate phage therapy cocktails to treat lung infections caused by P. aeruginosa. Here, we present an integrative structural atlas of Ar-KM proteins using cryo-EM, proteomics, and bioinformatics. From a single purified Ar-KM preparation, we identified three distinct populations: mature DNA-filled virions, open-nozzle particles with ejection proteins extending from the tail, and closed-nozzle empty particles. Near-atomic-resolution reconstructions of all three states enabled us to build atomic models for eleven structural proteins. The mature virion revealed the pre-ejection conformation of three ejection proteins, gp41, gp42, and gp43, homologous to coliphage T7's gp14, gp15, and gp16, respectively. Unlike T7, peptidoglycan hydrolase activity associated with the ejectosome resides in the gp15-like periplasmic tunnel protein gp42, whereas in T7 the lysozyme-like domain is located at the N-terminus of gp16, underscoring the structural plasticity and evolutionary mosaicity of ejection proteins. We further identified a short α-helical factor, gp34, present in eight copies at the mismatched interface between the portal barrel and gp41. Gp34 forms a cage within the nozzle, acting as a molecular wedge that stabilizes the open conformation and permits gp41 to assemble into a hexameric channel during ejection. Evolutionarily, gp34 appears to be an ortholog of the essential gene gp7.3 in phage T7 and is conserved across sequenced phiKMV-like phages. We propose that this protein functions as an ejection protein assembly factor, stabilizing the open nozzle during infection and allowing the coordinated exit of ejection proteins and their assembly into a DNA-ejectosome.

Pseudomonas phages↗
PubMed2025

Reversible phenotypic resistance to phage infection via capsule downregulation in Klebsiella pneumoniae.

Capsule loss is a major mechanism by which bacteria evade phage infection. This has traditionally been attributed to mutations in capsule biosynthesis genes. Here, we investigated phage resistance in Klebsiella pneumoniae, a medically relevant encapsulated bacterium. Phage infection rapidly selected for resistant acapsular cells. As expected, transcriptomic analysis revealed a marked downregulation of capsule biosynthesis genes. However, full genome sequencing showed that capsule loss occurred without evidence of mutations, and acapsular phage-resistant cells were able to rapidly restore their capsule once phage pressure was removed. These findings highlight that phage-driven selective pressure can act on non-heritable variation in gene expression, providing a faster and more flexible resistance mechanism compared to the traditional mutation-selection process. This reversible resistance may complicate predictability and limit the long-term efficacy of phage therapy.

Cell biology↗
PubMed2026

Mechanisms linking the gut microbiota to colorectal cancer development and progression.

Colorectal cancer remains a leading cause of global cancer mortality, with a concerning rise in early-onset cases driven by complex interactions between environmental exposures, lifestyle factors, and host genetics. Mounting evidence indicates that gut microbiota dysbiosis critically modulates this oncogenic process, acting as an active participant rather than a passive bystander. This review systematically synthesizes the dichotomous roles of the intestinal microbiome in colorectal tumorigenesis through the conceptual framework of the driver-passenger model. We discuss how early initiating driver bacteria, such as Polyketide synthase-positive Escherichia coli and enterotoxigenic Bacteroides fragilis, compromise mucosal barriers, induce chronic mucosal inflammation, and inflict direct genomic instability. As the local tumor microenvironment undergoes profound metabolic remodeling, opportunistic passenger pathogens, notably Fusobacterium nucleatum, become enriched, further promoting cellular proliferation and facilitating tumor immune evasion. Conversely, protective commensals, exemplified by Clostridium butyricum and Streptococcus thermophilus, exert robust tumor-suppressive effects through multifaceted mechanisms. These beneficial microbes actively antagonize malignant progression by redirecting tumor metabolic fluxes toward oxidative stress, orchestrating deep epigenetic reprogramming, and degrading core oncoproteins to reverse chemoresistance. Transitioning from fundamental mechanisms to clinical application, we evaluate a comprehensive spectrum of microbiota-targeted interventions, encompassing non-invasive diagnostic biomarkers, fecal microbiota transplantation, engineered bacteria, phage therapy, and postbiotics. Finally, we critically address the formidable translational challenges associated with microbial heterogeneity, long-term safety, and regulatory standardization, aiming to provide a balanced perspective on integrating microbiome-based strategies into next-generation precision oncology for colorectal cancer.

Humans↗
PubMed2025

NRG-P0074 Viral Sample RU1 from Unclassified Mosigvirus Genomic Characterization and Host Range Analysis.

BACKGROUND: Machine learning models for phage-host range prediction and design require comprehensive training data on phage genomes and host ranges to predict phage-host interactions effectively. MATERIALS AND METHODS: This study characterizes phage sample NRG-P0074 viral sample RU1 from unclassified Mosigvirus, originally isolated by the Betty Kutter. The complete genome of NRG-P0074 was sequenced, annotated, and analyzed using various bioinformatic tools. Host range analysis was conducted using the Escherichia coli Reference (ECOR) Library and nine Escherichia coli (E. coli) K12 strains (Keio Knockout Collection) with single nonessential gene deletions. RESULTS: The genome of NRG-P0074 spans 168,357 base pairs with a guanine-cytosine (GC) content of 37.5%. NRG-P0074 exhibited permissiveness in 15.28% of the ECOR isolates and all 9 Keio knockout strains. Comparative genomic analysis revealed that NRG-P0074 is closely related to E. coli phage a20. Its genome is comprised of 270 coding sequences, 153 known genes, 16 terminators, 3 ribosomal-binding sites, 0 tRNAs, and 117 hypothetical proteins. CONCLUSIONS: This research provides valuable data for developing machine learning models to predict phage-host interactions, aiding the development of targeted phage therapies against antibiotic-resistant bacteria.

ECOR Library↗
PubMed2025

The ecology and evolution of microbial immune systems: a look on the wild vibrio side.

Natural populations of vibrio beyond the well-studied pandemic strains of Vibrio cholerae, provide a powerful model for investigating the eco-evolutionary dynamics of microbial immune systems. Their genetic diversity, ecological versatility, ease of culturability and the availability of time-series data enable detailed studies of phage-host interactions in natural contexts. This review synthesizes recent advances in vibriophage research, highlighting key findings and emerging tools. High-throughput assays and genomic tools have offered new perspectives on phage specificity, host range and the evolutionary pressures shaping these interactions. Theoretical frameworks, such as arms race and fluctuating selection dynamics, are informed by empirical data from vibrio-phage systems, with time-series sampling providing crucial insights into their temporal and spatial dynamics. A major finding is the role of mobile genetic elements (MGEs) in encoding bacterial defence systems, which shape phage-host coevolution. Discoveries like the phage satellite PICMI illustrate how MGEs facilitate the transfer of antiviral systems, influencing ecological and evolutionary dynamics. The paradox of generalist vibriophages, rare despite their broad host ranges, is also explored. By integrating experimental approaches with field observations, vibriophage research advances microbial ecology and informs sustainable applications in aquaculture and phage therapy, reinforcing vibrios as a versatile model system.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.

Bacteriophages↗
PubMed2026

Genome sequences of six Enterobacter phages of the genus Karamvirus.

Here, we describe the genomes of six Enterobacter bacteriophages (phages) of the genus Karamvirus. The range of genome length, GC content, and number of predicted protein-coding sequences were, respectively, 171,900-175,675 bp, 39.54-39.82%, and 298-316. Genomic analysis indicates that these phages have a lytic lifestyle and are suitable for therapeutic use.

Enterobacter cloacae↗
PubMed2025

ABCD-type phage cocktail targeting distinct LPS receptor sites demonstrates superior efficacy against multidrug-resistant Salmonella.

The narrow host range of phages poses a limitation in addressing multidrug-resistant bacteria, whereas phage cocktail therapy, targeting multiple bacterial receptors, broadens the phage host spectrum. This study establishes a comprehensive Salmonella phages repository through nationwide surveillance in China, isolating 242 phages classified into 29 genera, with genome sizes ranging from 5.4 to 350.3 Kb. Based on LPS specificity, phages were categorized into four types A-D. Here, we developed an ABCD-Type phage cocktail targeting four distinct LPS recognition sites, demonstrating superior efficacy versus single phages or phage cocktail with different receptors (CCR-Type). In vitro, ABCD-Type phage cocktail treatment sustained bactericidal activity > 36 h versus CCR's 8 h, effectively controlling Salmonella in lettuce, milk, and Galleria mellonella infection models. Moreover, ABCD-Type phage cocktail effectively cleared Salmonella biofilms and showed promising results in the treatment of animal infections, significantly reducing bacterial loads in infected chicks and improving their survival rates. Resistant mutants predominantly harbored mutations in the btuB gene and LPS biosynthesis genes. These mutants showed increased antibiotic sensitivity and attenuated virulence. Collectively, these findings underscore the therapeutic potential of Salmonella phages, specifically ABCD-Type phage cocktail formulations which contain the phages PJNS014, PJNS023, PJNS036, and PJNS038, for controlling Salmonella infections. This work provides a foundation for developing advanced phage-based therapeutics.

Salmonella Phages↗
PubMed2025

Bacteriophages as a modern diagnostic tool: innovations, applications and challenges.

Bacteriophages, viruses that specifically infect bacteria, have emerged as a valuable tool in diagnostics due to their unique specificity and adaptability. This review explores the diverse applications of bacteriophages in diagnostic methods, from traditional phage typing to advanced molecular techniques such as phage display and PCR-based diagnostics. It highlights their use in identifying bacterial strains, monitoring fermentation processes, and diagnosing critical conditions like tuberculosis, MRSA infections, and cancer. Innovations such as phage-based biosensors and reporter phages enhance the speed and precision of diagnostics, offering significant advantages over traditional methods. Challenges, including bacterial resistance and immune responses to phages, are also discussed alongside strategies for mitigation, such as phage cocktails and engineering. Integrating phage technology with modern bioscience holds promise for addressing antibiotic resistance and revolutionizing clinical and industrial diagnostics. This comprehensive analysis underscores the potential of bacteriophages to transform the diagnostic landscape while identifying areas requiring further research and development.

Bacteriophages↗
PubMed2026

Achromobacter species in cystic fibrosis and chronic lung disease: a review of virulence, antibiotic resistance, diagnostic challenges, and emerging therapies.

Achromobacter species (spp) is an emerging opportunistic organism more frequently isolated from immunocompromised patients' and hospital settings. This bacterium was once considered an environmental bacterium, but now it is recognized as a serious cause of respiratory infections, bloodstream infections, and urinary tract infections, particularly among patients with cystic fibrosis (CF), chronic illnesses, and medical devices. The purpose of this review is to highlight Achromobacte's clinical significance, pathogenic mechanism, and recent approaches for diagnosis and treatment. By utilizing specific keywords relevant to Achromobacter spp., a comprehensive literature search was performed in PubMed and Google Scholar. To summarize existing knowledge and highlight gaps in the literature, peer-reviewed studies on clinical relevance, pathogenicity, antimicrobial resistance, and therapeutic approaches were gathered, screened, and narratively assembled. Among the 19 identified species, Achromobacter xylosoxidans (A. xylosoxidans) is the most prevalent and clinically relevant, especially in CF settings. This review explores the organism's microbiological characteristics, virulence strategies-including robust biofilm formation, motility, and secretion systems-and its alarming intrinsic and acquired resistance to antibiotics. Misidentification due to phenotypic overlap with other non-fermenting Gram-negative bacilli complicates diagnosis, while limited MALDI-TOF MS and database representation hinders species-level identification. Genotyping methods, including multi-locus sequence analysis and housekeeping gene sequencing, offer superior resolution but remain underutilized in clinical diagnostics. With rising resistance mediated by β-lactamases, efflux pumps, and adaptive genomic traits, Achromobacter spp presents a growing challenge for treatment and infection control. This review highlights the urgent need for improved diagnostic strategies, species-level clinical and microbiological data, and tailored therapeutic approaches to manage Achromobacter spp. infections effectively.

Humans↗
PubMed2026

Genomic characterization and therapeutic potential of five broad-spectrum lytic bacteriophages against multidrug-resistant avian pathogenic Escherichia coli (APEC).

UNLABELLED: Colibacillosis, caused by avian pathogenic Escherichia coli (APEC), results in substantial economic losses in global poultry production. The emergence of multidrug-resistant (MDR) APEC poses zoonotic risks through horizontal transfer of antimicrobial resistance (AMR) genes. Bacteriophage therapy emerges as a safe alternative to antibiotherapy; however, comprehensive characterization of phages targeting MDR-APEC from diverse geographical regions remains limited. We isolated five lytic bacteriophages from poultry fecal samples collected from five Indian states and characterized them through morphological analysis, physiological stability testing, whole-genome sequencing, and in vivo efficacy assessment. Host range was determined against APEC isolates, and therapeutic potential was validated in the Galleria mellonella infection model. All phages showed Myovirus-like morphology and stability across physiologically relevant temperatures (up to 55°C-70°C) and pH conditions (3-11). Phages were classified as Escherichia phage vB_EcoM_fRPOT1, vB_EcoM_fDMYT1, vB_EcoM_fBSZT1, vB_EcoM_fUAMT1, and vB_EcoM_fPKPT2. Their genome size ranges from 170 to 356 kb, belonging to three distinct genera: Dhakavirus, Gaprivervirus, and Asteriusvirus. Genomic analysis confirmed the absence of antimicrobial resistance, virulence, toxin, or lysogeny genes. Fifty-one APEC strains were isolated, of which 23 (45.1%) were MDR. Individual phages lysed 37%-51% of tested APEC and 17%-39% of MDR strains. Three phages (fBSZT1, fUAMT1, and fPKPT2) significantly improved larval survival to 60%-80% at an MOI of 10 in G. mellonella infection models compared to the untreated control. This study establishes a well-characterized phage bank targeting MDR-APEC strains, providing a foundation for developing phage-based interventions to reduce antibiotic dependency and mitigate AMR transmission risks under the One Health framework. IMPORTANCE: The overuse of antibiotics in poultry farming has created a crisis. The multidrug-resistant (MDR) bacteria threaten both animal health and human safety through the food chain. When antibiotics fail, farmers face devastating losses, and resistant bacteria can transfer to humans through consumption or environmental contamination. Bacteriophages offer a practical solution as they kill target bacteria without harming beneficial microbes or leaving chemical residues. Our comprehensive characterization confirms that these five phages are safe and effective as they lack any resistance or toxin genes and rescue 60%-80% of infected larvae. This represents a characterized phage bank targeting the specific resistant strains in Indian poultry. By providing a validated alternative to antibiotics, this work supports sustainable food production while reducing the spread of antimicrobial resistance from farms to humans.

Animals↗
PubMed2026

Genomic and functional characterization of novel therapeutic lytic bacteriophages targeting multidrug-resistant Enterobacter cloacae.

The alarming rates at which extensively drug-resistant (XDR) and pandrug-resistant (PDR) Enterobacter cloacae in hospitals are increasing has begun to severely limit treatment options, and thus the urgency for alternative interventions, including bacteriophage therapy. The purpose of the study was to isolate and molecularly characterize phages that can infect E. cloacae, and, furthermore, to assess the antimicrobial efficacy of the four novel lytic bacteriophages (MMRP1, MMRP2, MMRP3, and MMRP4) against antimicrobial-resistant E. cloacae isolates and to evaluate their potential as alternative therapeutic strategies. These novel phages were characterized by plaque morphology, transmission electron microscopy (TEM), host range testing, thermal and chloroform stability assays, bacterial reduction assays, and whole-genome sequencing (WGS). Among 27 clinical isolates, MDR, XDR, and PDR phenotypes were observed in 20 (74.1%), six (22.2%), and one (3.7%) isolates, respectively. All four phages produced clear lytic plaques (0.5-3.0 mm) with titers reaching up to 6 × 1010 PFU/mL, and the phage cocktail lysed 81.4% (22 of 27 isolates) of clinical isolates with high host specificity. TEM revealed that all four E. cloacae-infecting phages (MMRP1, MMRP2, MMRP3, and MMRP4) belong to the class Caudoviricetes, exhibiting icosahedral capsids, tailed morphology, and double-stranded DNA genomes, consistent with current ICTV classification criteria. Whole genome sequencing and comparative phylogenetic analysis further resolved the taxonomic placement of these phages at the family level, positioning MMRP1 within the family Demerecviridae and MMRP4 within the family Straboviridae. All phages were stable from -20 to 40 °C and were unaffected by exposure to chloroform. Phage cocktail reduced bacterial OD₆₀₀ to ≤ 0.3 within 4 h in the bacterial reduction test. WGS revealed large circular dsDNA genomes of ~132 kbp (MMRP1) and ~149 kbp (MMRP4), GC content of 38%, and modular architectures encoding structural, lytic, and replication gene modules. The most striking and highlighted suggestion that in vitro evaluation of MMRP1 and MMRP4 are highly recommended to more deeper future experimental studies to combat MDR E. cloacae nosocomial infections supported by genomic foundation and eventually, the possibility to be suitable for phage-engineering applications in clinical settings.

Enterobacter cloacae↗
PubMed2025

Isolation and characterization of bacteriophages from clinical enterohemorrhagic Escherichia coli strains.

Temperate bacteriophages play a pivotal role in the biology of their bacterial host. Of particular interest are bacteriophages infecting enterohemorrhagic E. coli (EHEC) due to their significant contribution to the pathogenicity of its host, most notably by encoding the key virulence factor of this pathogen, the Shiga toxin. To better understand the role of EHEC phages on the functionality of its host, we isolated eight temperate phages from clinical EHEC isolates and characterized their genomic composition, morphology, and receptor targeting. Morphological analysis identified one long-tailed siphophage, targeting the OmpC receptor for host recognition, whereas the other seven phages are short-tailed podophages and target the essential BamA protein. Genomic characterization revealed significant variations between the long- and short-tailed phages. Five of the eight isolated phages encode the potent Shiga toxin. Comparative analysis displays the typical lambdoid mosaicism, indicative of horizontal gene transfer driving evolution. These findings provide insights into the genetic and morphologic diversity and receptor specificity of EHEC phages, highlighting their role in the evolution and pathogenicity of clinical EHEC strains.IMPORTANCECharacterizing bacteriophages from clinical EHEC isolates is crucial in understanding the mechanisms underlying bacterial evolution and virulence. Despite the clinical relevance of EHEC bacteriophages, they remain underexplored, and particularly phage receptors are often not characterized. Studying temperate EHEC phages is essential in the development of strategies to address the global burden of these foodborne infections. Notably, identifying the phage receptors is critical in unraveling the specific interaction between phage and host. Knowledge of the phage receptors can provide insights into the mechanisms of phage infection, host range, and bacterial resistance and is fundamental in the design of targeted therapies like new antimicrobials, phage therapy, or prevention of those infections.

Humans↗
PubMed2026

Chronic suppression of a multidrug-resistant Pseudomonas aeruginosa in prosthetic joint infection using personalized bacteriophage treatment.

Multidrug resistant (MDR) bacterial infections without antibiotic options are a public health emergency. Infections associated with medical implants serve as an example. Conventional antibiotics have limited ability to eradicate these infections as they are associated with antibiotic-tolerant biofilms. Here, we report the use of bacteriophage therapy for the treatment of a MDR, non-operable Pseudomonas aeruginosa periprosthetic joint infection that had failed multiple antibiotic and surgical interventions. Treatment with intermittent bacteriophage therapy alone without antibiotics over a 2 year time period resulted in clinical resolution of the infection, but not microbiological eradication. Bacteriophage therapy established this control, in part, by altering virulence as defined by disease severity and symptoms and disrupting biofilm. Whole genome sequencing demonstrated the continued presence of bacteriophage during treatment. This provides preliminary evidence that bacteriophage therapy can be used to treat MDR infections in salvage cases when surgical and antibiotic options do not exist.

Humans↗
PubMed2026

Mutations in filamentous bacteriophages spark eco-evolutionary feedbacks in Pseudomonas aeruginosa.

Microbial populations strongly shape their environment, which can re-route adaptation toward organism-generated fitness optima. However, the conditions that promote these eco-evolutionary feedbacks are unclear. Here, we used experimental evolution to test whether high population density, by strengthening niche construction, drives eco-evolutionary feedbacks in the bacterial pathogen Pseudomonas aeruginosa (Pa) MPAO1. We tested for adaptation to organism-modified environments by measuring the relative performance of ancestral and endpoint populations in filtrate generated by each evolutionary line sampled across generations. Contrary to expectations, we found that endpoint populations had higher performance than the ancestral strain in filtrate across nearly all evolutionary lines regardless of population density. This was caused by the emergence of hyperactive filamentous bacterio(phage) mutants during experimental passaging that inhibited the ancestral strain but not endpoint populations in modified media. Hyperactive phages emerged from one of two avirulent prophages in MPAO1's genome (Pf4 or Pf6). Hyperactive phages drove the evolution of phage resistance in bacterial populations via mutations in the type IV pilus (TIVP), the phage's binding receptor. In a follow-up experiment, we showed that these TIVP mutations pleiotropically reduced motility and conferred resistance to a TIVP-targeting virulent phage, both of which are important traits for Pa infection and treatment. Overall, this work suggests that filamentous phage evolution can drive eco-evolutionary feedbacks in bacterial populations, causing phenotypic and genetic changes that would not be anticipated from adaptation to the extrinsic environment alone.

Pseudomonas aeruginosa↗