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Cell Host & Microbe

Ruben V Uribe, Eric van der Helm, Maria-Anna Misiakou, Sang-Woo Lee, Stefan Kol, Morten O A Sommer
CRISPR-Cas systems in bacteria and archaea provide immunity against bacteriophages and plasmids. To overcome CRISPR immunity, phages have acquired anti-CRISPR genes that reduce CRISPR-Cas activity. Using a synthetic genetic circuit, we developed a high-throughput approach to discover anti-CRISPR genes from metagenomic libraries based on their functional activity rather than sequence homology or genetic context. We identified 11 DNA fragments from soil, animal, and human metagenomes that circumvent Streptococcus pyogenes Cas9 activity in our selection strain...
January 31, 2019: Cell Host & Microbe
Clayton M Carey, Apurva A Govande, Juliane M Cooper, Melissa K Hartley, Philip J Kranzusch, Nels C Elde
Immune responses counteract infections but also cause collateral damage to hosts. Oligoadenylate synthetase 1 (OAS1) binds double-stranded RNA from invading viruses and produces 2'-5' linked oligoadenylate (2-5A) to activate ribonuclease L (RNase L), which cleaves RNA to inhibit virus replication. OAS1 can also undergo autoactivation by host RNAs, a potential trade-off to antiviral activity. We investigated functional variation in primate OAS1 as a model for how immune pathways evolve to mitigate costs and observed a surprising frequency of loss-of-function variation...
January 23, 2019: Cell Host & Microbe
Gustavo Caballero-Flores, Kei Sakamoto, Melody Y Zeng, Yaqiu Wang, Jill Hakim, Violeta Matus-Acuña, Naohiro Inohara, Gabriel Núñez
Owing to immature immune systems and impaired colonization resistance mediated by the microbiota, infants are more susceptible to enteric infections. Maternal antibodies can provide immunity, with maternal vaccination offering a protective strategy. We find that oral infection of adult females with the enteric pathogen Citrobacter rodentium protects dams and offspring against oral challenge. Parenteral immunization of dams with heat-inactivated C. rodentium reduces pathogen loads and mortality in offspring but not mothers...
January 21, 2019: Cell Host & Microbe
Robert Heler, Addison V Wright, Marija Vucelja, Jennifer A Doudna, Luciano A Marraffini
CRISPR-Cas systems provide acquired immunity in prokaryotes. Upon infection, short sequences from the phage genome, known as spacers, are inserted between the CRISPR repeats. Spacers are transcribed into small RNA molecules that guide nucleases to their targets. The forces that shape the distribution of newly acquired spacers, which is observed to be uneven, are poorly understood. We studied the spacer patterns that arise after phage infection of Staphylococcus aureus harboring the Streptococcus pyogenes type II-A CRISPR-Cas system...
January 14, 2019: Cell Host & Microbe
Simon A Jackson, Nils Birkholz, Lucía M Malone, Peter C Fineran
Many prokaryotes possess CRISPR-Cas adaptive immune systems to defend against viruses and invading mobile genetic elements. CRISPR-Cas immunity relies on genetic memories, termed spacers, for sequence-specific recognition of infections. The diversity of spacers within host populations is important for immune resilience, but we have limited understanding of how CRISPR diversity is generated. Type I CRISPR-Cas systems use existing spacers to enhance the acquisition of new spacers through primed CRISPR adaptation (priming)...
January 8, 2019: Cell Host & Microbe
Wael Elhenawy, Caressa N Tsai, Brian K Coombes
Crohn's disease (CD) is an inflammatory bowel disease influenced by bacteria. Adherent-invasive E. coli (AIEC) is associated with CD, yet the adaptations facilitating AIEC gut colonization are unknown. AIEC isolates exhibit high genetic diversity, suggesting strains evolve independently across different gut environments. We tracked the adaptive evolution of AIEC in a murine model of chronic colonization across multiple hosts and transmission events. We detected evolved lineages that outcompeted the ancestral strain in the host through independent mechanisms...
January 6, 2019: Cell Host & Microbe
Jee-Hwan Oh, Laura M Alexander, Meichen Pan, Kathryn L Schueler, Mark P Keller, Alan D Attie, Jens Walter, Jan-Peter van Pijkeren
The mammalian intestinal tract contains a complex microbial ecosystem with many lysogens, which are bacteria containing dormant phages (prophages) inserted within their genomes. Approximately half of intestinal viruses are derived from lysogens, suggesting that these bacteria encounter triggers that promote phage production. We show that prophages of the gut symbiont Lactobacillus reuteri are activated during gastrointestinal transit and that phage production is further increased in response to a fructose-enriched diet...
December 24, 2018: Cell Host & Microbe
Ernst Jonscher, Sven Flemming, Marius Schmitt, Ricarda Sabitzki, Nick Reichard, Jakob Birnbaum, Bärbel Bergmann, Katharina Höhn, Tobias Spielmann
During development in human erythrocytes, the malaria parasite Plasmodium falciparum internalizes a large part of the cellular content of the host cell. The internalized cytosol, consisting largely of hemoglobin, is transported to the parasite's food vacuole where it is degraded, providing nutrients and space for growth. This host cell cytosol uptake (HCCU) is crucial for parasite survival but the parasite proteins mediating this process remain obscure. Here, we identify P. falciparum VPS45 as an essential factor in HCCU...
December 14, 2018: Cell Host & Microbe
Pradeep D Uchil, Ruoxi Pi, Kelsey A Haugh, Mark S Ladinsky, John D Ventura, Brad S Barrett, Mario L Santiago, Pamela J Bjorkman, George Kassiotis, Xaver Sewald, Walther Mothes
Lymph- and blood-borne retroviruses exploit CD169/Siglec-1-mediated capture by subcapsular sinus and marginal zone metallophilic macrophages for trans-infection of permissive lymphocytes. However, the impact of CD169-mediated virus capture on retrovirus dissemination and pathogenesis in vivo is unknown. In a murine model of the splenomegaly-inducing retrovirus Friend virus complex (FVC) infection, we find that while CD169 promoted draining lymph node infection, it limited systemic spread to the spleen. At the spleen, CD169-expressing macrophages captured incoming blood-borne retroviruses and limited their spread to the erythroblasts in the red pulp where FVC manifests its pathogenesis...
December 12, 2018: Cell Host & Microbe
Daniel F Zegarra-Ruiz, Asmaa El Beidaq, Alonso J Iñiguez, Martina Lubrano Di Ricco, Silvio Manfredo Vieira, William E Ruff, Derek Mubiru, Rebecca L Fine, John Sterpka, Teri M Greiling, Carina Dehner, Martin A Kriegel
Western lifestyle is linked to autoimmune and metabolic diseases, driven by changes in diet and gut microbiota composition. Using Toll-like receptor 7 (TLR7)-dependent mouse models of systemic lupus erythematosus (SLE), we dissect dietary effects on the gut microbiota and find that Lactobacillus reuteri can drive autoimmunity but is ameliorated by dietary resistant starch (RS). Culture of internal organs and 16S rDNA sequencing revealed TLR7-dependent translocation of L. reuteri in mice and fecal enrichment of Lactobacillus in a subset of SLE patients...
December 7, 2018: Cell Host & Microbe
Yingnan Hou, Yi Zhai, Li Feng, Hana Z Karimi, Brian D Rutter, Liping Zeng, Du Seok Choi, Bailong Zhang, Weifeng Gu, Xuemei Chen, Wenwu Ye, Roger W Innes, Jixian Zhai, Wenbo Ma
RNA silencing (RNAi) has a well-established role in anti-viral immunity in plants. The destructive eukaryotic pathogen Phytophthora encodes suppressors of RNAi (PSRs), which enhance plant susceptibility. However, the role of small RNAs in defense against eukaryotic pathogens is unclear. Here, we show that Phytophthora infection of Arabidopsis leads to increased production of a diverse pool of secondary small interfering RNAs (siRNAs). Instead of regulating endogenous plant genes, these siRNAs are found in extracellular vesicles and likely silence target genes in Phytophthora during natural infection...
December 1, 2018: Cell Host & Microbe
Benoît-Joseph Laventie, Matteo Sangermani, Fabienne Estermann, Pablo Manfredi, Rémi Planes, Isabelle Hug, Tina Jaeger, Etienne Meunier, Petr Broz, Urs Jenal
The opportunistic human pathogen Pseudomonas aeruginosa effectively colonizes host epithelia using pili as primary adhesins. Here we uncover a surface-specific asymmetric virulence program that enhances P. aeruginosa host colonization. We show that when P. aeruginosa encounters surfaces, the concentration of the second messenger c-di-GMP increases within a few seconds. This leads to surface adherence and virulence induction by stimulating pili assembly through activation of the c-di-GMP receptor FimW. Surface-attached bacteria divide asymmetrically to generate a piliated, surface-committed progeny (striker) and a flagellated, motile offspring that leaves the surface to colonize distant sites (spreader)...
December 1, 2018: Cell Host & Microbe
Pa Wu, Peng Sun, Kaixiao Nie, Yibin Zhu, Mingyu Shi, Changguang Xiao, Han Liu, Qiyong Liu, Tongyan Zhao, Xiaoguang Chen, Hongning Zhou, Penghua Wang, Gong Cheng
Mosquitoes are hematophagous vectors that can acquire human viruses in their intestinal tract. Here, we define a mosquito gut commensal bacterium that promotes permissiveness to arboviruses. Antibiotic depletion of gut bacteria impaired arboviral infection of a lab-adapted Aedes aegypti mosquito strain. Reconstitution of individual cultivable gut bacteria in antibiotic-treated mosquitoes identified Serratia marcescens as a commensal bacterium critical for efficient arboviral acquisition. S. marcescens facilitates arboviral infection through a secreted protein named SmEnhancin, which digests membrane-bound mucins on the mosquito gut epithelia, thereby enhancing viral dissemination...
November 28, 2018: Cell Host & Microbe
Shirin Moossavi, Shadi Sepehri, Bianca Robertson, Lars Bode, Sue Goruk, Catherine J Field, Lisa M Lix, Russell J de Souza, Allan B Becker, Piushkumar J Mandhane, Stuart E Turvey, Padmaja Subbarao, Theo J Moraes, Diana L Lefebvre, Malcolm R Sears, Ehsan Khafipour, Meghan B Azad
Breastmilk contains a complex community of bacteria that may help seed the infant gut microbiota. The composition and determinants of milk microbiota are poorly understood. Among 393 mother-infant dyads from the CHILD cohort, we found that milk microbiota at 3-4 months postpartum was dominated by inversely correlated Proteobacteria and Firmicutes, and exhibited discrete compositional patterns. Milk microbiota composition and diversity were associated with maternal factors (BMI, parity, and mode of delivery), breastfeeding practices, and other milk components in a sex-specific manner...
February 13, 2019: Cell Host & Microbe
Lasha Gogokhia, Kate Buhrke, Rickesha Bell, Brenden Hoffman, D Garrett Brown, Christin Hanke-Gogokhia, Nadim J Ajami, Matthew C Wong, Arevik Ghazaryan, John F Valentine, Nathan Porter, Eric Martens, Ryan O'Connell, Vinita Jacob, Ellen Scherl, Carl Crawford, W Zac Stephens, Sherwood R Casjens, Randy S Longman, June L Round
Bacteriophages are the most abundant members of the microbiota and have the potential to shape gut bacterial communities. Changes to bacteriophage composition are associated with disease, but how phages impact mammalian health remains unclear. We noted an induction of host immunity when experimentally treating bacterially driven cancer, leading us to test whether bacteriophages alter immune responses. Treating germ-free mice with bacteriophages leads to immune cell expansion in the gut. Lactobacillus, Escherichia, and Bacteroides bacteriophages and phage DNA stimulated IFN-γ via the nucleotide-sensing receptor TLR9...
February 13, 2019: Cell Host & Microbe
J Leonardo Moreno-Gallego, Shao-Pei Chou, Sara C Di Rienzi, Julia K Goodrich, Timothy D Spector, Jordana T Bell, Nicholas D Youngblut, Ian Hewson, Alejandro Reyes, Ruth E Ley
The virome is one of the most variable components of the human gut microbiome. Within twin pairs, viromes have been shown to be similar for infants, but not for adults, indicating that as twins age and their environments and microbiomes diverge, so do their viromes. The degree to which the microbiome drives the vast virome diversity is unclear. Here, we examine the relationship between microbiome and virome diversity in 21 adult monozygotic twin pairs selected for high or low microbiome concordance. Viromes derived from virus-like particles are unique to each individual, are dominated by Caudovirales and Microviridae, and exhibit a small core that includes crAssphage...
February 13, 2019: Cell Host & Microbe
Kaitlyn E Kortright, Benjamin K Chan, Jonathan L Koff, Paul E Turner
Phage therapy, long overshadowed by chemical antibiotics, is garnering renewed interest in Western medicine. This stems from the rise in frequency of multi-drug-resistant bacterial infections in humans. There also have been recent case reports of phage therapy demonstrating clinical utility in resolving these otherwise intractable infections. Nevertheless, bacteria can readily evolve phage resistance too, making it crucial for modern phage therapy to develop strategies to capitalize on this inevitability. Here, we review the history of phage therapy research...
February 13, 2019: Cell Host & Microbe
Luisa De Sordi, Marta Lourenço, Laurent Debarbieux
The intestinal microbiota is intimately linked to human health. Decoding the mechanisms underlying its stability in healthy subjects should uncover causes of microbiota-associated diseases and pave the way for treatment. Bacteria and bacteriophages (phages) are the most abundant biological entities in the gastrointestinal tract, where their coexistence is dynamic and affixed. Phages drive and maintain bacterial diversity by perpetuating the coevolutionary interactions with their microbial prey. This review brings together recent in silico, in vitro, and in vivo work dissecting the complexity of phage-bacteria interactions in the intestinal microbiota, including coevolution perspectives...
February 13, 2019: Cell Host & Microbe
Andrey N Shkoporov, Colin Hill
The human gut microbiome is a dense and taxonomically diverse consortium of microorganisms. While the bacterial components of the microbiome have received considerable attention, comparatively little is known about the composition and physiological significance of human gut-associated bacteriophage populations (phageome). By extrapolating our knowledge of phage-host interactions from other environments, one could expect that >1012 viruses reside in the human gut, and we can predict that they play important roles in regulating the complex microbial networks operating in this habitat...
February 13, 2019: Cell Host & Microbe
Jakob T Rostøl, Luciano Marraffini
Bacteria are under constant attack from bacteriophages (phages), bacterial parasites that are the most abundant biological entity on earth. To resist phage infection, bacteria have evolved an impressive arsenal of anti-phage systems. Recent advances have significantly broadened and deepened our understanding of how bacteria battle phages, spearheaded by new systems like CRISPR-Cas. This review aims to summarize bacterial anti-phage mechanisms, with an emphasis on the most recent developments in the field.
February 13, 2019: Cell Host & Microbe
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