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Sundberg, L.-R.

Publications and source records attributed to Sundberg, L.-R..

16 recordsLinked to original sources

Boreal and subarctic freshwaters harbour a diversity of jumbophages

Bacteriophages (phages) are major drivers of microbial evolution and ecology, yet their diversity and functional roles remain poorly characterised in many natural environments, such as in freshwater systems. In boreal and subarctic freshwater habitats, where bacteria are typically slow-growing and nutrient-limited, phages are predicted to have a critical role in host regulation and horizontal gene exchange. However, only a few isolates have been obtained from such environments, leaving the genetic and functional diversity of these phages largely unexplored. Here, we present a collection of 40 bacteriophages isolated from boreal lakes and rivers using a set of diverse freshwater bacterial hosts. Despite using conventional isolation methods, eight of the isolates possess genomes larger than 200 kilobases and are classified as jumbophages. All jumbophages exhibited myovirus morphology and comparatively slow infection dynamics. These jumbophages include the first known representatives infecting members of Janthinobacterium and Herbaspirillum. Comparative genomic and phylogenetic analyses show that nearly all genomes are distinct from previously described phages, indicating substantial novelty. Diverse auxiliary metabolic and anti-defence systems were identified, including putative NAD+ salvage and acyl carrier protein modules, along with predicted Anti-Thoeris and Anti-CBASS elements. The Pseudomonas-infecting jumbophage Ahti encoded homologues of all 21 core genes that define the nucleus-forming family Chimalliviridae. Additionally, Ahti displayed compartmentalisation of DNA during infection, establishing it as the first freshwater nucleus-forming phage. These findings expand our understanding of the ecological, genomic, and functional diversity of phages in boreal environments, and highlight the role of freshwater ecosystems as significant reservoirs of novel viral lineages. ImportanceBacteriophages are viruses that infect bacteria and play important roles in shaping microbial communities and nutrient cycling in natural waters. However, much of what is known about their diversity comes from sequencing data alone, without environmental isolates that allow direct studies on their biology. In this study, we described 40 bacteriophages from boreal and subarctic lakes and rivers using freshwater bacterial hosts, including species of Flavobacterium, Pseudomonas, Janthinobacterium and other lesser-known phage hosts. Eight of these viruses had exceptionally large genomes, categorising them as jumbophages. These isolates included the first known jumbophages infecting Janthinobacterium and Herbaspirillum, as well as the first freshwater jumbophage shown to form a nucleus-like structure during infection. Together, these findings reveal boreal freshwaters as an important source of previously unknown virus diversity and provide new model systems for exploring phage biology in environmentally relevant contexts.

microbiology↗

Mucin modulates phage infection dynamics and biofilm formation in enteropathogenic Yersinia enterocolitica

Mucosal barriers serve as a multifunctional interface and nutrient-rich habitat for diverse microbes, including bacteria and bacteriophages. Some phages can bind to mucin glycoproteins via carbohydrate-interacting modules and provide an additional layer of mucosal immunity by shielding the underlying epithelium from invading bacteria. However, the role of mucins in shaping phage-bacterium interactions remains poorly understood. We investigated the dynamics between highly pathogenic Yersinia enterocolitica serotype O:8 and its mucus-adherent phage fMtkYen801 under in vitro mucosal environment. We assessed how mucin supplementation, varying phage doses, nutrient and temperature conditions influence phage-bacterium dynamics and biofilm formation. We found that pre-exposure to mucins led to enhanced phage replication in the bacterial host, with a 2-log increase in phage titers, and high abundance of surviving bacteria. Interestingly, mucin glycoproteins also provided Y. enterocolitica a nutrient source and a chemical cue to modulate its growth and biofilm biogenesis. Genomic analysis of phage-resistant bacterial variants revealed mutations in virulence, quorum sensing, and antibiotic resistance genes in both mucin enrichment and control groups, suggesting potential fitness tradeoffs during resistance evolution. Collectively, these findings highlight the importance of mucosal surfaces as an important ecological driver of phage-host interactions in Y. enterocolitica, a significant enteric pathogen, and emphasize the need for investigating these dynamics under complex, physiologically relevant systems to inform better phage therapy strategies against mucosal bacterial infections.

microbiology↗

Mucin-enriched environment shapes bacteriophage protection against Pseudomonas aeruginosa in airway epithelial cells

Mucin hypersecretion, a hallmark of chronic respiratory diseases (CRD), creates a complex microenvironment that reshapes host immunity and microbial behavior. However, its impact on bacteriophage therapy remains poorly understood. Here, we demonstrate that, despite reducing Pseudomonas aeruginosa internalization, exogenous mucin increases bacterial-induced cytotoxicity and inflammation in airway epithelial cells, while driving CRD-like transcriptional changes, including hypoxia and stress responses. Under bacterial culture, mucin selectively downregulates bacterial virulence factors without impairing growth. P. aeruginosa-infecting bacteriophage DMS3vir retains full lytic activity in mucin-rich conditions and, in synergy with mucin, enhances protection against cytotoxicity in epithelial cells. DMS3vir also reduces IL-8 gene expression without triggering antiviral responses. Furthermore, mucin supplementation shapes phage-resistant P. aeruginosa phenotypes, altering colony pigmentation, pyocyanin production, and motility, influencing virulence trade-offs. These findings uncover the dual role of mucins as modulators of infection and sensitizers to phage protection, paving the way for optimized, mucosa-adapted phage therapies in chronic lung diseases.

microbiology↗

ssDNA phage FLiP resides in dsDNA form in resistant Flavobacterium host

Most of the environmental flavobacteria decompose organic matter, playing a crucial role in ecosystem balance. Phages infecting these bacteria regulate the host populations and thereby the ecosystem functions, however, bacterial resistance against phage may cause changes in bacterial phenotypic characteristics. ssDNA phage Finnlakevirus FLiP infects three known environmental Flavobacterium sp. isolates: B330, B167, and B114. Building on our previous FLiP-host interaction studies, we aimed to broaden our understanding of the host perspective by exploring phage resistance mechanisms against FLiP and similar phages. We compared growth dynamics of ancestral and resistant variants to detect the effect of resistance on host fitness. Genomic comparison between the variants was used to identify resistance-related mutations. Additionally, we analysed genomic differences among the three host strains, screening for anti-phage systems. Sequence analyses, PCR, and nuclease treatments of resistant host genomes and plasmids were used to assess the possibility of lysogeny and superinfection immunity. No single mutation or anti-phage system consistently explained FLiP resistance, as these varied across hosts. Resistant B114 contained FLiP genome in circular extrachromosomal dsDNA form, suggesting possible lysogeny. Surprisingly, we found that low quantities of FLiP sequences exist in bacterial populations not exposed to FLiP in the laboratory. This suggests that residing as extrachromosomal dsDNA elements in a small percentage of host cells may be a natural strategy for FLiP type phages to endure unfavourable conditions.

microbiology↗

New Finnlakevirus isolate FLiP-2 provides insight into the ecology of ssDNA phages in Flavobacterium hosts

Life cycle details or ecological impact are well characterized only for a few ssDNA phages. The Finnlakeviridae family includes one species, Finnlakevirus FLiP. Here, using the same Flavobacterium host and sampling location, we isolated a new strain designated FLiP-2, with 96,7 % genetic identity to the original isolate FLiP. To understand the ecology of this Flavobacterium-infecting phage species, we explored the host interactions of the two FLiP strains and a dsDNA Flavobacterium phage MaF61 under various conditions representing those encountered in their natural habitats in boreal lakes including different temperatures, anoxic conditions, and in the presence of different nutrients and antibiotics. While FLiP and FLiP-2 had similar virion stability outside the host, they exhibited significant differences in plaque morphology and infectivity. FLiP-2 could not replicate in the presence of ampicillin, whereas FLiP thrived even at high concentrations. Both strains of Finnlakevirus FLiP propagated better under or after stress exposure compared to MaF61. Additionally, Finnlakevirus FLiP plaques appeared far from the original infection site, particularly in response to stress, suggesting latent presence within a motile or filamentous bacterium. In conclusion, Finnlakevirus FLiP showed remarkable flexibility in host-interactions being well adapted to fluctuating conditions in boreal freshwaters.

microbiology↗

Longitudinal dynamics of gut plasmidome and antibiotic resistance during antibiotic therapy: a case report

The human gut microbiome is composed of diverse microbes, and its association with human health is well-recognized. Antibiotic therapies for treating infectious diseases often mediate adverse influences on gut microbial ecosystems. Further, ESBL (extended-spectrum beta-lactamase)-producing bacteria potentially residing in the gut benefit from antibiotic-induced environmental changes via positive selection for resistance traits. As antimicrobial resistance (AMR) genes are often harbored by mobile plasmids, the importance of these extrachromosomal mobile genetic elements during antibiotic exposure is evident. However, there is still a knowledge gap in how microbiomes respond to antibiotic treatment especially in terms of plasmid carriage and how gut plasmid populations evolve following and revive after antibiotic therapy. To address these questions, in this case report we investigated the changes in plasmid population in the gut microbiome of a single ESBL-carrying patient during antibiotic therapy for uncomplicated acute appendicitis. Employing longitudinal sampling, we collected E. coli strains and performed metagenomic analysis before, during, and after the treatment. Our findings indicate that the antibiotic treatment is associated with a transient alteration in the microbial composition, AMR profile, and plasmid population. An extensive but temporary domination of ESBL-E. coli within the gut microbiome was observed parallel to the ongoing antibiotic treatment. However, this was not sustained in the follow-up period, indicating a slight restoration of both the microbial composition and the plasmid population. The research underscores the temporary impact of antibiotic therapy on the dynamics of the gut plasmidome which essentially mediate the spread of AMR within the gut microbiome.

microbiology↗

Genomic and structural insights into Jyvaskylavirus, the first giant virus isolated from Finland

Giant viruses of protists are a diverse and likely ubiquitous group of organisms. Here, we describe Jyvaskylavirus, the first giant virus isolated from Finland. This clade B marseillevirus was found in Acanthamoeba castellanii from a composting soil sample in Jyvaskyla, Central Finland. Its genome shares similarities with other marseilleviruses. Helium ion microscopy and electron microscopy of infected cells unraveled stages of the Jyvaskylavirus lifecycle. We reconstructed the Jyvaskylavirus particle to 6.3 [A] resolution using cryo-EM. The [~]2,500 [A] diameter virion displays structural similarities to other Marseilleviridae giant viruses. The capsid comprises of 9,240 copies of the major capsid protein ORF184, which possesses a double jellyroll fold arranged in trimers forming pseudo-hexameric capsomers. Below the capsid shell, the internal membrane vesicle encloses the genome. Through cross-structural and -sequence comparisons with other Marseilleviridae using AI-based software in model building and prediction, we elucidated ORF142 as the penton protein, which plugs the twelve vertices of the capsid. Five additional ORFs were identified, with models predicted and fitted into densities that either cap the capsomers externally or stabilize them internally. The isolation of Jyvaskylavirus suggests that these viruses may be widespread in the boreal environment and provide structural insights extendable to other marseilleviruses.

microbiology↗

New Vista into Origins of Viruses from a Prototypic ssDNA Phage

Viruses play a central role in all ecological niches; the origin of viruses, however, remains an open question. While phylogenetic analysis of distantly related viruses is hampered by a lack of detectable sequence similarity, structural biology can reveal conserved capsid protein structures that facilitate the study of distant evolutionary relationships. Here, we characterize the lipid-containing ssDNA temperate bacteriophage {Phi}CjT23, which is infecting Flavobacterium sp. (Bacteroidetes). We further detected {Phi}CjT23-like sequences in the genome of strains belonging to several Flavobacterium species. The virion structure determined by cryogenic electron microscopy revealed similarities to members of the viral kingdom Bamfordvirae that currently consists solely of dsDNA viruses. Common to these viruses, infecting hosts from all domains of life, is a major capsid protein composed of two upright {beta}-sandwiches. The minimalistic structure of {Phi}CjT23 suggests that this phage serves as a model for the last common ancestor between ssDNA and dsDNA viruses in the Bamfordvirae. Both {Phi}CjT23 and the related phage FLiP infect Flavobacterium species found in several environments, suggesting that these types of viruses have a global distribution and shared evolutionary origin. Detailed comparisons to related, more complex viruses not only expand our knowledge about this group of viruses but also provide a rare glimpse into early virus evolution.

microbiology↗

Mucin induces CRISPR-Cas defence in an opportunistic pathogen

Parasitism by bacteriophages has led to the evolution of a variety of defense mechanisms in their host bacteria. However, it is unclear what factors lead to specific defenses being deployed upon phage infection. To explore this question, we exposed the bacterial fish pathogen Flavobacterium columnare to its virulent phage V156 in the presence of a eukaryotic host signal (mucin). All tested conditions led to some level of innate immunity, but the presence of mucin led to a dramatic increase in CRISPR spacer acquisition, especially in low nutrient conditions where over 60% of colonies had obtained at least one new spacer. Additionally, we show that the presence of a competitor bacterium further increases CRISPR spacer acquisition in F. columnare. These results suggest that ecological factors are important in determining defense strategies against phages, and that the concentration of phages on metazoan surfaces may select for the diversification of bacterial immune systems.

microbiology↗

Bacteriophage Resistance Affects Flavobacterium columnare Virulence Partly via Mutations in Genes Related to Gliding Motility and Type IX Secretion System

Increasing problems with antibiotic resistance has directed interest towards phages as tools to treat bacterial infections in the aquaculture industry. However, phage resistance evolves rapidly in bacteria posing a challenge for successful phage therapy. To investigate phage resistance in the fish pathogenic bacterium Flavobacterium columnare, two phage-sensitive, virulent wild-type isolates, FCO-F2 and FCO-F9, were exposed to phages and subsequently analyzed for bacterial viability and colony morphology. Twenty-four phage-exposed isolates were further characterized for phage resistance, antibiotic susceptibility, motility, adhesion and biofilm formation on polystyrene surface, protease activity, whole genome sequencing and virulence against rainbow trout fry. Bacterial viability first decreased in the exposure cultures, subsequently increasing after 1-2 days. Simultaneously, the colony morphology of the phage-exposed isolates changed from original rhizoid to rough. The rough isolates arising in phage exposure were phage-resistant with low virulence, whereas rhizoid isolates maintained phage sensitivity, though reduced, and high virulence. Gliding motility and protease activity were also related to the phage sensitivity. Observed genetic mutations in phage-resistant isolates were mostly located in genes coding for type IX secretion system, a component of the flavobacterial gliding motility machinery. However, there were mutational differences between individual isolates, and not all phage-resistant isolates had genetic mutations. This indicates that development of phage resistance in F. columnare probably is a multifactorial process including both genetic mutations and changes in gene expression. Phage resistance may not, however, be a challenge for development of phage therapy against F. columnare infections, since phage resistance is associated with decrease in bacterial virulence. ImportancePhage resistance of infectious bacteria is a common phenomenon posing challenges for development of phage therapy. Along with growing World population and need for increased food production, constantly intensifying animal farming has to face increasing problems of infectious diseases. Columnaris disease, caused by F. columnare, is a worldwide threat for salmonid fry and juvenile farming. Without antibiotic treatments, infections can lead to 100% mortality in a fish stock. Phage therapy of columnaris disease would reduce a development of antibiotic-resistant bacteria and antibiotic loads by the aquaculture industry, but phage-resistant bacterial isolates may become a risk. However, phenotypic and genetic characterization of phage-resistant F. columnare isolates in this study revealed that they are less virulent than phage-sensitive isolates and thus not a challenge for phage therapy against columnaris disease. This is a valuable information for the fish farming industry globally when considering phage-based prevention and curing methods for F. columnare infections.

microbiology↗

Prevalence of genetically similar Flavobacterium columnare phages across aquaculture environments reveals a strong potential for pathogen control

Intensive aquaculture conditions expose fish to bacterial infections, leading to significant financial losses, extensive antibiotic use and risk of antibiotic resistance in target bacteria. Flavobacterium columnare causes columnaris disease in aquaculture worldwide. To develop a bacteriophage-based control of columnaris disease, we isolated and characterized 126 F. columnare strains and 63 phages against F. columnare from Finland and Sweden. Bacterial isolates were virulent on rainbow trout (Oncorhynchus mykiss) and fell into four previously described genetic groups A, C, E and G, with genetic groups C and E being the most virulent. Phage host range studied against a collection of 228 bacterial isolates demonstrated modular infection patterns based on host genetic group. Phages infected contemporary and previously isolated bacterial hosts, but bacteria isolated most recently were generally resistant to previously isolated phages. Despite large differences in geographical origin, isolation year or host range of the phages, whole genome sequencing of 56 phages showed high level of genetic similarity to previously isolated F. columnare phages (Ficleduovirus, Myoviridae). Altogether, this phage collection demonstrates a potential to be used in phage therapy. Significance StatementBacteriophages were discovered already over a century ago, and used widely in treatment of bacterial diseases before the era of antibiotics. Due to harmful effects of antibiotic leakage into environment, aquaculture is a potential target for phage therapy. However, the development of efficient phage therapy approach requires detailed characterization of bacterial pathogen virulence and phage host range. Here, we describe phage-bacterium interactions in the fish pathogen Flavobacterium columnare. We found that genetically similar phages are found from different fish farms, and their infectivity cluster according to genetic group of bacteria. In addition, phages were able to infect bacterial hosts from other farms, which is a preferable trait considering phage therapy approach. However, the most recently isolated phages had broader host range than the previously isolated phages, suggesting a response in the phage community to evolution of resistance in the bacteria. These results show that designing phage therapy for aquaculture (and other) systems needs consideration of both temporal and geographical aspects of the phage-bacterium interaction.

microbiology↗

Rich resource environment of fish farms facilitates phenotypic variation and virulence in an opportunistic fish pathogen

Phenotypic variation allows adaptation of opportunistic pathogens to variable conditions in the outside-host environment with strong effects on their epidemiology and pathogenicity in hosts. Here we found that the isolates of an opportunistic fish pathogen Flavobacterium columnare from fish farming environment had higher phenotypic variation between two morphotypes in growth, as compared to the isolates from the natural water environment. The rough morphotypes had higher growth rate than the rhizoid morphotypes especially in the higher resource concentrations and in the higher temperature, but only if the isolate was originating from the fish farms. Rhizoid morphotype was more virulent than the rough type regardless of their origin. However, the virulence of the rough type increased sharply with the size of the fish, and the bacterial isolates from the gills of diseased fish were rhizoid type, indicating a reversal of the rough morphotype into rhizoid in contact with the fish. The high growth rate of the rough morphotype combined with the morphotype reversibility could increase the probability of columnaris epidemics at fish farms. Our findings suggest that intensive farming imposes different selection pressures on bacterial survival in the outside-host environment and its transmission compared to the natural water environment.

microbiology↗

Cooperation between CRISPR-Cas types enables adaptation in an RNA-targeting system

CRISPR-Cas immune systems adapt to new threats by acquiring spacers from invading nucleic acids such as phage genomes. However, some CRISPR-Cas loci lack genes necessary for spacer acquisition, despite apparent variation in spacer content between strains. It has been suggested that such loci may use acquisition machinery from co-occurring CRISPR-Cas systems. Here, using a lytic dsDNA phage, we observe spacer acquisition in the native host Flavobacterium columnare that carries an acquisition-deficient subtype VI-B locus and a complete subtype II-C locus. We characterize acquisition events in both loci and show that the RNA-targeting VI-B locus acquires spacers in trans using acquisition machinery from the DNA-targeting II-C locus. Our observations reinforce the concept of modularity in CRISPR-Cas systems and raise further questions regarding plasticity of adaptation modules.

microbiology↗

Bacteriophage adherence to mucus mediates preventive protection against pathogenic bacteria

Metazoan mucosal surfaces are major interfaces between the organism and environment. These surfaces have been proposed to host bacteriophages in a symbiotic relationship with metazoans. Considering the so far poorly understood phage-mucus interaction and its role in ecological interactions and for mucosal bacterial infections, empirical evidence and model systems need to be established. Here, using the fish pathogen Flavobacterium columnare and rainbow trout (Oncorhynchus mykiss), we show that phages infecting the pathogen are capable of binding to primary mucus layers and protecting fish from infections. Furthermore, exposure to mucus changes the bacterial phenotype by increasing bacterial virulence and susceptibility to phage infections. Tests using other phage-bacterium pairs suggest that the relevance of mucus for bacteria and phages may be widespread in the biosphere. Therefore, interactions of bacteria and phages inside the mucus environment may be important for disease and evolution, and this phenomenon has significant potential to be exploited for preventive phage therapy approaches.

microbiology↗

Thermal Tolerance is linked with Virulence in a Fish Pathogen

Although increase in temperatures may boost the number of pathogens, a complex process involving the interaction of a susceptible host, a virulent strain, and environmental factors would influence disease virulence in unpredictable ways. Here we explored if the virulence of an environmentally growing opportunistic fish pathogen, Flavobacterium columnare, would be malleable to evolutionary changes via correlated selection on thermal tolerance. Virulence among the strains increased over years, but tolerance to higher temperatures was associated with reduced virulence. Our results suggest that observed increase in frequency of columnaris epidemics over the last decade is most likely associated with increased length of growing season, or other time dependent change in environment, rather than increased regional average temperatures. Our results also indicate that most virulent bacteria had weaker ability to tolerate outside host environments, which suggest trade-off between more obligate pathogen behaviour and ability to grow outside host.

evolutionary biology↗

Long-term genomic coevolution of host-parasite interaction in natural environment

The antagonistic coevolution of parasite infectivity and host resistance alters the biological functionality of species, with effects spanning to communities and ecosystems. Still, studies describing long-term host-parasite coevolutionary dynamics in nature are largely missing. Furthermore, the role of host resistance mechanisms for parasite evolution is poorly understood, necessitating for the molecular and phenotypic characterization of both coevolving parasites and their hosts. We combined long-term field sampling (2007-2014), in vitro cross-infections and time-shift experiments with bacteriophage whole genome sequencing and bacterial (Flavobacterium columnare) CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) profiling to show the molecular details of the phage-bacterium arms race in the environment. Bacteria were generally resistant to phages from the past and susceptible to phages in the future. The bacterial resistance selected for increased phage infectivity and host range, correlating directly with the expansion of phage genome size by 2656 bp. In the bacterial host, two CRISPR loci were identified: a type II-C locus and an RNA-targeting type VI-B locus. While maintaining a core set of conserved spacers, phage-matching spacers appeared in the variable end of both CRISPR loci over time. The appearance of these CRISPR spacers in the bacterial host often corresponded with arms race -manner molecular changes in the protospacers of the coevolving phage population. However, the phenotypic data indicated that the relative role of constitutive defence may be more important in high phage pressure, highlighting the importance of our findings for understanding microbial community ecology and in the development of phage therapy applications.

microbiology↗