Long-term persistence of crAss-like phage crAss001 is associated with phase variation in Bacteroides intestinalis

The crAss-like phages are ubiquitous and highly abundant members of the human gut virome that infect commensal bacteria of the order Bacteroidales. Although incapable of classical lysogeny, these viruses demonstrate unexplained long-term persistence in the human gut microbiome, dominating the virome in some individuals. Here we demonstrate that rapid phase variation of alternate capsular polysaccharides plays an important role in dynamic equilibrium between phage sensitivity and resistance in B. intestinalis cultures, allowing phage and bacteria to multiply in parallel. The data also suggests the role of concomitant phage persistence mechanisms associated with delayed lysis of infected cells, such as carrier state infection. From an ecological and evolutionary standpoint this type of phage-host interaction is consistent with the Piggyback-the-Winner model, which suggests a preference towards lysogenic or other 'benign' forms of phage infection when the host is stably present at high abundance.

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Long-term persistence of crAss-like phage crAss001 is associated with phase variation in Bacteroides intestinalis

BMC Biology ◽

10.1186/s12915-021-01084-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Andrey N. Shkoporov ◽

Ekaterina V. Khokhlova ◽

Niamh Stephens ◽

Cara Hueston ◽

Samuel Seymour ◽

...

Keyword(s):

Dynamic Equilibrium ◽

Phase Variation ◽

Carrier State ◽

Complex Environments ◽

Human Gut ◽

Rapid Phase ◽

Host Interaction ◽

Infected Cells ◽

Phage Sensitivity

Abstract Background The crAss-like phages are ubiquitous and highly abundant members of the human gut virome that infect commensal bacteria of the order Bacteroidales. Although incapable of lysogeny, these viruses demonstrate long-term persistence in the human gut microbiome, dominating the virome in some individuals. Results Here we show that rapid phase variation of alternate capsular polysaccharides in Bacteroides intestinalis cultures plays an important role in a dynamic equilibrium between phage sensitivity and resistance, allowing phage and bacteria to multiply in parallel. The data also suggests the role of a concomitant phage persistence mechanism associated with delayed lysis of infected cells, similar to carrier state infection. From an ecological and evolutionary standpoint, this type of phage-host interaction is consistent with the Piggyback-the-Winner model, which suggests a preference towards lysogenic or other “benign” forms of phage infection when the host is stably present at high abundance. Conclusion Long-term persistence of bacteriophage and host could result from mutually beneficial mechanisms driving bacterial strain-level diversity and phage survival in complex environments.

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Bluetongue in Europe and the role of wildlife in the epidemiology of disease

Polish Journal of Veterinary Sciences ◽

10.1515/pjvs-2015-0060 ◽

2015 ◽

Vol 18 (2) ◽

pp. 455-461 ◽

Cited By ~ 7

Author(s):

W. Niedbalski

Keyword(s):

Roe Deer ◽

Natural Infection ◽

Carrier State ◽

Clinical Disease ◽

Domestic Sheep ◽

African Buffalo ◽

Wild Sheep ◽

South Eastern Europe

Abstract The article reviews a current bluetongue (BT) epidemiological situation in Europe, BT restricted zones and the role of wild ungulates as a reservoir for bluetongue virus (BTV) and its transmission. BT has been eradicated from central and northern Europe, however it is still circulating in some regions of southern and south-eastern Europe. According to the recent information of the Directoriate General for Health and Consumer Affairs (DG SANCO) disease caused by BTV1 was spreading at the beginning of 2014 in Corsica (France). Moreover, four BTV1 cases were noticed in the west Spain (Cáceres province), 59 BTV4 outbreaks in south Spain (Andalusia), 10 in the region of Algarve in Portugal and about 200 outbreaks of BTV4 in Greece (Peloponesse and Evros regions). On 4th July the first outbreak of BTV4 was also confirmed at the south Bulgarian border and by 5th September 2014 disease was noticed in 21 of 28 administrative districts of Bulgaria. In August 2014 the BTV4 disease was reported in south-east of Romania and as for 8th September 184 outbreaks of BT were confirmed in 17 counties of this country. As of 3 September 2014 in Europe there has been fourteen BT-affected zones, in different regions of Italy, Spain, Portugal, Cyprus, Malta, France (Corsica), Greece, Bulgaria and Romania. Most species of wild ruminants and camelids are susceptible to BTV infection, although frequently asymptomatically. Wild sheep, bighorn and mouflon, are susceptible to BTV infection and can develop fatal clinical disease, as do domestic sheep. Experimental or natural infection of antelope, wapiti, musk, ox, bison, yak, white-tailed deer and African buffalo also produced clinical disease, whereas blesbock, mountain gazelle, roe deer, red deer and Eurasian elk did not show clinical sign after natural or experimental infection and infection was recognized by the presence of BTV viral RNA or specific antibodies. The wildlife due to the long-term carrier state may act as a reservoir for BTV and play an important role in its transmission.

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The Janus-faced role of KDM5B heterogeneity in melanoma: differentiation as a situational driver of both growth arrest and drug-resistance

10.1101/2020.04.01.999847 ◽

2020 ◽

Author(s):

Heike Chauvistré ◽

Sheena M. Daignault ◽

Batool Shannan ◽

Robert J. Ju ◽

Daniel Picard ◽

...

Keyword(s):

Cell Differentiation ◽

Drug Exposure ◽

Dynamic Equilibrium ◽

Melanoma Cells ◽

Tumor Plasticity ◽

Histone H3k4 ◽

Slow Cycling ◽

Tumor Cell Differentiation

AbstractPhenotypic intratumoral heterogeneity and temporal transitions between cell differentiation states represent major drivers of tumor fitness in melanoma. Expression of the histone H3K4 demethylase KDM5B/JARID1B follows a highly dynamic equilibrium across melanoma cells. When challenged for example with targeted or cytotoxic drugs, the intrinsically slow-cycling KDM5Bhigh cell state becomes initially enriched, whereas under persistent drug-exposure melanomas decrease KDM5B expression again to re-enter cell proliferation for long-term tumor repopulation. However, the exact role of KDM5B for tumor cell differentiation and fate remained elusive so far. Here, we show that melanoma fitness can be overcome by molecular enforcement of high KDM5B expression levels. KDM5B-up-scaled melanoma cells are transcriptionally reprogramed towards a differentiated melanocytic profile including a slow-cycling state. This effect can be phenocopied by a newly identified chemical compound also leading to decelerated tumor growth. Mechanistically, KDM5B represents a checkpoint for coordinating the differentiation phenotype of melanoma cells via transcriptional reprograming, cell cycle delay, and attenuation of cytokinetic abscission. These findings indicate that tumor plasticity per se, i.e. the necessity of cancer cells to dynamically switch between different cell cycling and differentiation states, represents an important oncologic process that can be chemically overcome.

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Virioplankton as an important component of plankton in the Volga Reservoirs

Biosystems Diversity ◽

10.15421/012120 ◽

2021 ◽

Vol 29 (2) ◽

pp. 151-159

Author(s):

A. I. Kopylov ◽

E. A. Zabotkina

Keyword(s):

Heterotrophic Bacteria ◽

Viral Lysis ◽

Bacterioplankton Production ◽

Viral Particles ◽

Digestible Organic Matter ◽

Volga Reservoirs ◽

Infected Cells ◽

Production Frequency

The distribution of virioplankton, abundance and production, frequency of visibly infected cells of heterotrophic bacteria and autotrophic picocyanobacteria and their virus-induced mortality have been studied in mesotrophic and eutrophic reservoirs of the Upper and Middle Volga (Ivankovo, Uglich, Rybinsk, Gorky, Cheboksary, and Sheksna reservoirs). The abundance of planktonic viruses (VA) is on average by 4.6 ± 1.2 times greater than the abundance of bacterioplankton (BA). The distribution of VA in the Volga reservoirs was largely determined by the distribution of BA and heterotrophic bacterioplankton production (PB). There was a positive correlation between VA and BA and between VA and PB. In addition, BA and VA were both positively correlated with primary production of phytoplankton. Viral particles of 60 to 100 µm in size dominated in the phytoplankton composition. A large number of bacteria and picocyanobacteria with viruses attached to the surface of their cells were found in the reservoirs. Viruses as the most numerous component of plankton make a significant contribution to the formation of the planktonic microbial community biomass. The number of phages inside infected cells of bacteria and picocyanobacteria reached 74‒109 phages/cell. Easily digestible organic matter, which entered the aquatic environment as a result of viral lysis of bacteria and picocyanobacteria, could be an additional source of carbon for living bacteria. The results of long-term studies indicate a significant role of viruses in functioning of planktonic microbial communities in the Volga reservoirs.

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Recipients withIn UteroInduction of Tolerance Upregulated MHC Class I in the Engrafted Donor Skin

Disease Markers ◽

10.1155/2014/531092 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9

Author(s):

Jeng-Chang Chen ◽

Liang-Shiou Ou ◽

Hsiu-Yueh Yu ◽

Ming-Ling Kuo ◽

Pei-Yeh Chang ◽

...

Keyword(s):

Mhc Class I ◽

Class I ◽

Quantitative Real Time Pcr ◽

Biological Phenomenon ◽

Short Term ◽

Donor Skin ◽

Gene Transcripts ◽

Infected Cells

The alterations in MHC class I expression play a crucial step in immune evasion of cancer or virus-infected cells. This study aimed to examine whether tolerized grafts modified MHC class I expression. FVB/N mice were rendered tolerant of C57BL/6 alloantigens byin uterotransplantation of C57BL/6 marrows. Postnatally, engrafted donor skins and leukocytes were examined for their MHC expression by quantitative real-time PCR and flow cytometry. Engrafted donor skins upregulated their MHC class I related gene transcripts after short-term (1~2 weeks) or long-term (>1 month) engraftment. This biological phenomenon was simultaneously associated with upregulation of TAP1 gene transcripts, suggesting an important role of TAP1 in the regulation of MHC class I pathway. The surface MHC class I molecules of H-2Kbin engrafted donor leukocytes consistently showed overexpression. Conclusively, the induction of allograft tolerance involved biological modifications of donor transplants. The overexpression of MHC class I within engrafted transplants of tolerant mice might be used as the tolerance biomarkers for identifying a state of graft tolerance.

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The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study

mBio ◽

10.1128/mbio.02634-20 ◽

2020 ◽

Vol 11 (6) ◽

Author(s):

N. V. Patin ◽

A. Peña-Gonzalez ◽

J. K. Hatt ◽

C. Moe ◽

A. Kirby ◽

...

Keyword(s):

Gut Microbiome ◽

Host Susceptibility ◽

Host Responses ◽

Human Gut ◽

Important Data ◽

Challenge Study ◽

Recovery Times ◽

Asymptomatic Infections

ABSTRACT Norovirus infections take a heavy toll on worldwide public health. While progress has been made toward understanding host responses to infection, the role of the gut microbiome in determining infection outcome is unknown. Moreover, data are lacking on the nature and duration of the microbiome response to norovirus infection, which has important implications for diagnostics and host recovery. Here, we characterized the gut microbiomes of subjects enrolled in a norovirus challenge study. We analyzed microbiome features of asymptomatic and symptomatic individuals at the genome (population) and gene levels and assessed their response over time in symptomatic individuals. We show that the preinfection microbiomes of subjects with asymptomatic infections were enriched in Bacteroidetes and depleted in Clostridia relative to the microbiomes of symptomatic subjects. These compositional differences were accompanied by differences in genes involved in the metabolism of glycans and sphingolipids that may aid in host resilience to infection. We further show that microbiomes shifted in composition following infection and that recovery times were variable among human hosts. In particular, Firmicutes increased immediately following the challenge, while Bacteroidetes and Proteobacteria decreased over the same time. Genes enriched in the microbiomes of symptomatic subjects, including the adenylyltransferase glgC, were linked to glycan metabolism and cell-cell signaling, suggesting as-yet unknown roles for these processes in determining infection outcome. These results provide important context for understanding the gut microbiome role in host susceptibility to symptomatic norovirus infection and long-term health outcomes. IMPORTANCE The role of the human gut microbiome in determining whether an individual infected with norovirus will be symptomatic is poorly understood. This study provides important data on microbes that distinguish asymptomatic from symptomatic microbiomes and links these features to infection responses in a human challenge study. The results have implications for understanding resistance to and treatment of norovirus infections.

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Synchronized HIV assembly by tunable PIP2 changes reveals PIP2 requirement for stable Gag anchoring

eLife ◽

10.7554/elife.25287 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 21

Author(s):

Frauke Mücksch ◽

Vibor Laketa ◽

Barbara Müller ◽

Carsten Schultz ◽

Hans-Georg Kräusslich

Keyword(s):

Chemical Biology ◽

Dynamic Equilibrium ◽

Experimental System ◽

Site Formation ◽

Structural Protein ◽

Infected Cells ◽

New Protein ◽

Hiv 1 ◽

Assembly Site

HIV-1 assembles at the plasma membrane (PM) of infected cells. PM association of the main structural protein Gag depends on its myristoylated MA domain and PM PI(4,5)P2. Using a novel chemical biology tool that allows rapidly tunable manipulation of PI(4,5)P2 levels in living cells, we show that depletion of PI(4,5)P2 completely prevents Gag PM targeting and assembly site formation. Unexpectedly, PI(4,5)P2 depletion also caused loss of pre-assembled Gag lattices from the PM. Subsequent restoration of PM PI(4,5)P2 reinduced assembly site formation even in the absence of new protein synthesis, indicating that the dissociated Gag molecules remained assembly competent. These results reveal an important role of PI(4,5)P2 for HIV-1 morphogenesis beyond Gag recruitment to the PM and suggest a dynamic equilibrium of Gag-lipid interactions. Furthermore, they establish an experimental system that permits synchronized induction of HIV-1 assembly leading to induced production of infectious virions by targeted modulation of Gag PM targeting.

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