scholarly journals Mucin induces CRISPR-Cas defence in an opportunistic pathogen

2021 ◽  
Author(s):  
Gabriel MF Almeida ◽  
Ville Hoikkala ◽  
Janne J Ravantti ◽  
Noora Rantanen ◽  
Lotta-Riina Sundberg
Keyword(s):  
Defense Mechanisms ◽  
Ecological Factors ◽  
Opportunistic Pathogen ◽  
Flavobacterium Columnare ◽  
Fish Pathogen ◽  
Defense Strategies ◽  
Virulent Phage ◽  
Immune Systems ◽  
Bacterial Immune Systems ◽  
Host Signal

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.

scholarly journals Molecular Basis of Citrus sunki Susceptibility and Poncirus trifoliata Resistance Upon Phytophthora parasitica Attack

2018 ◽  
Vol 31 (3) ◽  
pp. 386-398 ◽  
Author(s):  
Ronaldo José Durigan Dalio ◽  
Heros José Máximo ◽  
Tiago Silva Oliveira ◽  
Thamara de Medeiros Azevedo ◽  
Henrique Leme Felizatti ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Defense Mechanisms ◽  
Time Course ◽  
Poncirus Trifoliata ◽  
Disease Development ◽  
Phytophthora Parasitica ◽  
Defense Strategies ◽  
Molecular Core ◽  
Pathogen Effector ◽  
Plant Pathogen Interactions

Coevolution has shaped the molecular basis of an extensive number of defense mechanisms in plant-pathogen interactions. Phytophthora parasitica, a hemibiothrophic oomycete pathogen and the causal agent of citrus root rot and gummosis, interacts differently with Citrus sunki and Poncirus trifoliata, two commonly favored citrus rootstocks that are recognized as susceptible and resistant, respectively, to P. parasitica. The molecular core of these interactions remains elusive. Here, we provide evidence on the defense strategies employed by both susceptible and resistant citrus rootstocks, in parallel with P. parasitica deployment of effectors. Time course expression analysis (quantitative real-time polymerase chain reaction) of several defense-related genes were evaluated during i) plant disease development, ii) necrosis, and iii) pathogen effector gene expression. In C. sunki, P. parasitica deploys effectors, including elicitins, NPP1 (necrosis-inducing Phytophthora protein 1), CBEL (cellulose-binding elicitor and lectin activity), RxLR, and CRN (crinkler), and, consequently, this susceptible plant activates its main defense signaling pathways that result in the hypersensitive response and necrosis. Despite the strong plant-defense response, it fails to withstand P. parasitica invasion, confirming its hemibiothrophic lifestyle. In Poncirus trifoliata, the effectors were strongly expressed, nevertheless failing to induce any immunity manipulation and disease development, suggesting a nonhost resistance type, in which the plant relies on preformed biochemical and anatomical barriers.

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

2020 ◽  
Author(s):  
Katja Pulkkinen ◽  
Tarmo Ketola ◽  
Jouni Laakso ◽  
Johanna Mappes ◽  
Lotta-Riina Sundberg
Keyword(s):  
Growth Rate ◽  
Natural Water ◽  
Phenotypic Variation ◽  
Water Environment ◽  
High Growth ◽  
Flavobacterium Columnare ◽  
Bacterial Survival ◽  
Fish Pathogen ◽  
Fish Farms ◽  
Host Environment

SummaryPhenotypic 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.

scholarly journals A direct RNA-protein interaction atlas of the SARS-CoV-2 RNA in infected human cells

2020 ◽  
Author(s):  
Nora Schmidt ◽  
Caleb A. Lareau ◽  
Hasmik Keshishian ◽  
Randy Melanson ◽  
Matthias Zimmer ◽  
...  
Keyword(s):  
Viral Replication ◽  
Host Defense ◽  
Drug Targets ◽  
Defense Mechanisms ◽  
Human Cells ◽  
Genome Replication ◽  
Defense Strategies ◽  
Novel Therapeutic Strategies ◽  
Global Threat ◽  
Research Challenge

ABSTRACTSARS-CoV-2 infections pose a global threat to human health and an unprecedented research challenge. Among the most urgent tasks is obtaining a detailed understanding of the molecular interactions that facilitate viral replication or contribute to host defense mechanisms in infected cells. While SARS-CoV-2 co-opts cellular factors for viral translation and genome replication, a comprehensive map of the host cell proteome in direct contact with viral RNA has not been elucidated. Here, we use RNA antisense purification and mass spectrometry (RAP-MS) to obtain an unbiased and quantitative picture of the human proteome that directly binds the SARS-CoV-2 RNA in infected human cells. We discover known host factors required for coronavirus replication, regulators of RNA metabolism and host defense pathways, along with dozens of potential drug targets among direct SARS-CoV-2 binders. We further integrate the SARS-CoV-2 RNA interactome with proteome dynamics induced by viral infection, linking interactome proteins to the emerging biology of SARS-CoV-2 infections. Validating RAP-MS, we show that CNBP, a regulator of proinflammatory cytokines, directly engages the SARS-CoV-2 RNA. Supporting the functional relevance of identified interactors, we show that the interferon-induced protein RYDEN suppresses SARS-CoV-2 ribosomal frameshifting and demonstrate that inhibition of SARS-CoV-2-bound proteins is sufficient to manipulate viral replication. The SARS-CoV-2 RNA interactome provides an unprecedented molecular perspective on SARS-CoV-2 infections and enables the systematic dissection of host dependency factors and host defense strategies, a crucial prerequisite for designing novel therapeutic strategies.

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

2020 ◽  
Author(s):  
Ville Hoikkala ◽  
Janne Ravantti ◽  
César Díez-Villaseñor ◽  
Marja Tiirola ◽  
Rachel A. Conrad ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Flavobacterium Columnare ◽  
Immune Systems ◽  
Dna Targeting ◽  
B Locus ◽  
Rna Targeting ◽  
In Trans ◽  
Apparent Variation ◽  
Dsdna Phage ◽  
Native Host

AbstractCRISPR-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.

scholarly journals Leptin signaling regulates physiological damage and host-pathogen cooperation

2020 ◽  
Author(s):  
Karina K. Sanchez ◽  
Katia Troha ◽  
Sarah Stengel ◽  
Janelle S. Ayres
Keyword(s):  
Defense Mechanisms ◽  
Yersinia Pseudotuberculosis ◽  
Far East ◽  
Organ Damage ◽  
Resistance Mechanisms ◽  
Defense Strategies ◽  
Leptin Signaling ◽  
Host Pathogen ◽  
Cooperative Defense ◽  
Additional Level

ABSTRACTTo combat infections, hosts employ a combination of antagonistic and cooperative defense strategies. The former refers to pathogen killing mediated by resistance mechanisms, while the latter refers to physiological defense mechanisms that promote host health during infection independent of pathogen killing, leading to an apparent cooperation between the host and the pathogen. Previous work has shown that leptin, a pleiotropic hormone that plays a central role in regulating appetite and energy metabolism, is indispensable for resistance mechanisms, while a role for leptin signaling in cooperative host-pathogen interactions remains unknown. Using a mouse model of Yersinia pseudotuberculosis (Yptb) infection, the causative agent of Far East scarlet-like fever, we unexpectedly found that genetic inhibition of leptin signaling conferred protection from Yptb infection due to increased host-pathogen cooperation rather than greater resistance defenses. The protection against Yptb infection was not due to differences in food consumption, lipolysis or fat mass. Furthermore, we found that the survival advantage was associated with increased liver damage and dysfunction. Our work reveals an additional level of complexity for the role of leptin in infection defense and suggests that in some contexts, in addition to tolerating the pathogen, tolerating organ damage and dysfunction is more beneficial for survival than preventing the damage.

scholarly journals Complete Genome Sequence of Fish Pathogen Flavobacterium columnare Strain B185, Originating from Finland

2019 ◽  
Vol 8 (49) ◽  
Author(s):  
Janne J. Ravantti ◽  
Elina Laanto ◽  
Petri Papponen ◽  
Lotta-Riina Sundberg
Keyword(s):  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Flavobacterium Columnare ◽  
Fish Pathogen ◽  
Sequencing Technology ◽  
Content Type ◽  
Pacbio Rs Ii ◽  
Circular Genome

We report a complete genome sequence of a Finnish isolate of the fish pathogen Flavobacterium columnare. Using PacBio RS II sequencing technology, the complete circular genome of F. columnare strain B185 with 3,261,404 bp was obtained.

scholarly journals Prophages and Past Prophage-Host Interactions Revealed by CRISPR Spacer Content in a Fish Pathogen

2020 ◽  
Vol 8 (12) ◽  
pp. 1919
Author(s):  
Elina Laanto ◽  
Janne J. Ravantti ◽  
Lotta-Riina Sundberg
Keyword(s):  
Flavobacterium Columnare ◽  
Strain Atcc ◽  
Human Pathogens ◽  
Fish Pathogen ◽  
Bacterial Strains ◽  
Host Interactions ◽  
Different Strains ◽  
Gene Orthologs ◽  
Similar Genome Organization

The role of prophages in the evolution, diversification, or virulence of the fish pathogen Flavobacterium columnare has not been studied thus far. Here, we describe a functional spontaneously inducing prophage fF4 from the F. columnare type strain ATCC 23463, which is not detectable with commonly used prophage search methods. We show that this prophage type has a global distribution and is present in strains isolated from Finland, Thailand, Japan, and North America. The virions of fF4 are myoviruses with contractile tails and infect only bacterial strains originating from Northern Finland. The fF4 resembles transposable phages by similar genome organization and several gene orthologs. Additional bioinformatic analyses reveal several species in the phylum Bacteroidetes that host a similar type of putative prophage, including bacteria that are important animal and human pathogens. Furthermore, a survey of F. columnare Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) spacers indicate a shared evolutionary history between F. columnare strains and the fF4 phage, and another putative prophage in the F. columnare strain ATCC 49512, named p49512. First, CRISPR spacer content from the two CRISPR loci (types II-C and VI-B) of the fF4 lysogen F. columnare ATCC 23463 revealed a phage terminase protein-matching spacer in the VI-B locus. This spacer is also present in two Chinese F. columnare strains. Second, CRISPR analysis revealed four F. columnare strains that contain unique spacers targeting different regions of the putative prophage p49512 in the F. columnare strain ATCC 49512, despite the geographical distance or genomovar of the different strains. This suggests a common ancestry for the F. columnare prophages and different host strains.

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