The Spatial Heterogeneity of the Gut Limits Predation and Fosters Coexistence of Bacteria and Bacteriophages.
eux L, De Sordi L Abstract The ecological dynamics underlying the coexistence between antagonistic populations of bacteria and their viruses, bacteriophages (phages), in the mammalian gut microbiota remain poorly understood. We challenged a murine synthetic bacterial community with phages to study the factors allowing phages-bacteria coexistence. Coexistence was not dependent on the development of phage-resistant clones nor on the ability of phages to extend their host range. Instead, our data suggest that phage-inaccessible sites in the mucosa serve as a spatial refuge for bacteria. From there, bacteria dissemina...
Source: Cell Host and Microbe - June 29, 2020 Category: Microbiology Authors: Lourenço M, Chaffringeon L, Lamy-Besnier Q, Pédron T, Campagne P, Eberl C, Bérard M, Stecher B, Debarbieux L, De Sordi L Tags: Cell Host Microbe Source Type: research

Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike.
uart DI Abstract There are as yet no licensed therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2, initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralizing SARS-CoV-2, and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilizing CR3022 epitope is inaccessible in ...
Source: Cell Host and Microbe - June 19, 2020 Category: Microbiology Authors: Huo J, Zhao Y, Ren J, Zhou D, Duyvesteyn HME, Ginn HM, Carrique L, Malinauskas T, Ruza RR, Shah PNM, Tan TK, Rijal P, Coombes N, Bewley KR, Tree JA, Radecke J, Paterson NG, Supasa P, Mongkolsapaya J, Screaton GR, Carroll M, Townsend A, Fry EE, Owens RJ, S Tags: Cell Host Microbe Source Type: research

Cholesterol Metabolism by Uncultured Human Gut Bacteria Influences Host Cholesterol Level.
Abstract The human microbiome encodes extensive metabolic capabilities, but our understanding of the mechanisms linking gut microbes to human metabolism remains limited. Here, we focus on the conversion of cholesterol to the poorly absorbed sterol coprostanol by the gut microbiota to develop a framework for the identification of functional enzymes and microbes. By integrating paired metagenomics and metabolomics data from existing cohorts with biochemical knowledge and experimentation, we predict and validate a group of microbial cholesterol dehydrogenases that contribute to coprostanol formation. These enzymes ar...
Source: Cell Host and Microbe - June 10, 2020 Category: Microbiology Authors: Kenny DJ, Plichta DR, Shungin D, Koppel N, Hall AB, Fu B, Vasan RS, Shaw SY, Vlamakis H, Balskus EP, Xavier RJ Tags: Cell Host Microbe Source Type: research

Nourishing the Microbiota to Promote Mucosal Immunity.
Abstract Childhood undernutrition is associated with dysbiosis and dampened vaccine responses. Understanding how nutrients influence the microbiota and immunity is critical for vaccine efficacy. In this issue of Cell Host & Microbe, Di Luccia et al. and Huus et al. reveal that nutrition affects IgA responses to the microbiota and oral vaccines. PMID: 32526178 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - June 10, 2020 Category: Microbiology Authors: Shenoy MK, Koch MA Tags: Cell Host Microbe Source Type: research

Toxin Glycan Binding: Lectin Keys Unlocking Host and Tissue Specificity.
Abstract In this issue of Cell Host and Microbe, Lee et al. define the glycan binding specificity of a variant of typhoid toxin produced by a non-typhoidal Salmonellae serotype. The authors elegantly demonstrate that tissue and host specificity of the toxin are related to specific glycan binding characteristics of the toxin. PMID: 32526179 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - June 10, 2020 Category: Microbiology Authors: Petersen E, Miller SI Tags: Cell Host Microbe Source Type: research

IgA Summons IgG to Take a Hit at HIV-1.
Abstract In this issue of Cell Host & Microbe, Jia et al. used a vesicular stomatitis virus-based probe to isolate B cells expressing broadly neutralizing HIV-1 antibodies. Besides identifying neutralizing epitopes, this study highlights potential protection afforded by IgA arising from either direct IgM-to-IgA or sequential IgM-to-IgG-to-IgA class switching. PMID: 32526180 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - June 10, 2020 Category: Microbiology Authors: Magri G, Cerutti A Tags: Cell Host Microbe Source Type: research

MARVellous Sidekick Antibodies.
Abstract Human monoclonal antibodies are immune weapons that hold great promise for treating Marburg virus (MARV) infection. In this issue, Ilinykh et al. unveil non-neutralizing inhibitory properties of antibodies to the Wing region of the viral spike, which alongside with neutralizers are pivotal to in vivo protection against MARV infection. PMID: 32526181 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - June 10, 2020 Category: Microbiology Authors: Mouquet H Tags: Cell Host Microbe Source Type: research

Call to Action: How to Tackle Emerging Nosocomial Fungal Infections.
Abstract Nosocomial fungal infections require a robust scientific response to complement antifungal development and the implementation of infection control measures. This Commentary discusses how a parallel effort to address fungal pathogenesis and antifungal immunity, the mycobiota and colonization resistance, and risk factors is essential to reduce the toll of these infections. PMID: 32526182 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - June 10, 2020 Category: Microbiology Authors: Lionakis MS, Hohl TM Tags: Cell Host Microbe Source Type: research

Clostridioides difficile Senses and Hijacks Host Heme for Incorporation into an Oxidative Stress Defense System.
ar EP Abstract Clostridioides difficile infection of the colon leads to severe inflammation and damage to the gastrointestinal epithelium due to the production of potent toxins. This inflammatory tissue damage causes the liberation of high concentrations of host heme at infection sites. Here, we identify the C. difficile heme-sensing membrane protein system (HsmRA) and show that this operon induces a protective response that repurposes heme to counteract antimicrobial oxidative stress responses. HsmR senses vertebrate heme, leading to increased expression of the hsmRA operon and subsequent deployment of HsmA ...
Source: Cell Host and Microbe - June 7, 2020 Category: Microbiology Authors: Knippel RJ, Wexler AG, Miller JM, Beavers WN, Weiss A, de Crécy-Lagard V, Edmonds KA, Giedroc DP, Skaar EP Tags: Cell Host Microbe Source Type: research

The Serotonin Neurotransmitter Modulates Virulence of Enteric Pathogens.
Abstract The gut-brain axis is crucial to microbial-host interactions. The neurotransmitter serotonin is primarily synthesized in the gastrointestinal (GI) tract, where it is secreted into the lumen and subsequently removed by the serotonin transporter, SERT. Here, we show that serotonin decreases virulence gene expression by enterohemorrhagic E. coli (EHEC) and Citrobacter rodentium, a murine model for EHEC. The membrane-bound histidine sensor kinase, CpxA, is a bacterial serotonin receptor. Serotonin induces dephosphorylation of CpxA, which inactivates the transcriptional factor CpxR controlling expression ...
Source: Cell Host and Microbe - June 4, 2020 Category: Microbiology Authors: Kumar A, Russell RM, Pifer R, Menezes-Garcia Z, Cuesta S, Narayanan S, MacMillan JB, Sperandio V Tags: Cell Host Microbe Source Type: research

A Combination of Human Broadly Neutralizing Antibodies against Hepatitis B Virus HBsAg with Distinct Epitopes Suppresses Escape Mutations.
ovic M, Robbiani DF, Wen Y, de Jong YP, Rice CM, Nussenzweig MC Abstract Although there is no effective cure for chronic hepatitis B virus (HBV) infection, antibodies are protective and correlate with recovery from infection. To examine the human antibody response to HBV, we screened 124 vaccinated and 20 infected, spontaneously recovered individuals. The selected individuals produced shared clones of broadly neutralizing antibodies (bNAbs) that targeted 3 non-overlapping epitopes on the HBV S antigen (HBsAg). Single bNAbs protected humanized mice against infection but selected for resistance mutations in mice wit...
Source: Cell Host and Microbe - June 3, 2020 Category: Microbiology Authors: Wang Q, Michailidis E, Yu Y, Wang Z, Hurley AM, Oren DA, Mayer CT, Gazumyan A, Liu Z, Zhou Y, Schoofs T, Yao KH, Nieke JP, Wu J, Jiang Q, Zou C, Kabbani M, Quirk C, Oliveira T, Chhosphel K, Zhang Q, Schneider WM, Jahan C, Ying T, Horowitz J, Caskey M, Jan Tags: Cell Host Microbe Source Type: research

Jasmonate Signaling Enhances RNA Silencing and Antiviral Defense in Rice.
Abstract Small RNA-mediated RNA silencing is an important antiviral mechanism in higher plants. It has been shown that RNA silencing components can be upregulated by viral infection. However, the mechanisms underlying the upregulation remain largely unknown. Here, we show that jasmonate (JA) signaling transcriptionally activates Argonaute 18 (AGO18), a core RNA silencing component that promotes rice antiviral defense through sequestering miR168 and miR528, which repress key antiviral defense proteins. Mechanistically, the JA-responsive transcription factor JAMYB directly binds to the AGO18 promoter to activate AGO...
Source: Cell Host and Microbe - June 1, 2020 Category: Microbiology Authors: Yang Z, Huang Y, Yang J, Yao S, Zhao K, Wang D, Qin Q, Bian Z, Li Y, Lan Y, Zhou T, Wang H, Liu C, Wang W, Qi Y, Xu Z, Li Y Tags: Cell Host Microbe Source Type: research

CD31 (PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin.
CD31 (PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin. Cell Host Microbe. 2020 May 29;: Authors: Bruggisser J, Tarek B, Wyder M, Müller P, von Ballmoos C, Witz G, Enzmann G, Deutsch U, Engelhardt B, Posthaus H Abstract Clostridium perfringens β-toxin (CPB) is a highly active β-pore-forming toxin (β-PFT) and the essential virulence factor for fatal, necro-hemorrhagic enteritis in animals and humans. The molecular mechanisms involved in CPB's action on its target, the endothelium of small intestinal vessels, are poorly understood. Her...
Source: Cell Host and Microbe - May 29, 2020 Category: Microbiology Authors: Bruggisser J, Tarek B, Wyder M, Müller P, von Ballmoos C, Witz G, Enzmann G, Deutsch U, Engelhardt B, Posthaus H Tags: Cell Host Microbe Source Type: research

Functional and Genomic Variation between Human-Derived Isolates of Lachnospiraceae Reveals Inter- and Intra-Species Diversity.
Abstract Bacteria belonging to the Lachnospiraceae family are abundant, obligate anaerobic members of the microbiota in healthy humans. Lachnospiraceae impact their hosts by producing short-chain fatty acids, converting primary to secondary bile acids, and facilitating colonization resistance against intestinal pathogens. To increase our understanding of genomic and functional diversity between members of this family, we cultured 273 Lachnospiraceae isolates representing 11 genera and 27 species from human donors and performed whole-genome sequencing assembly and annotation. This analysis revealed substantial inte...
Source: Cell Host and Microbe - May 27, 2020 Category: Microbiology Authors: Sorbara MT, Littmann ER, Fontana E, Moody TU, Kohout CE, Gjonbalaj M, Eaton V, Seok R, Leiner IM, Pamer EG Tags: Cell Host Microbe Source Type: research

A Mouse Model of SARS-CoV-2 Infection and Pathogenesis.
In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studyi...
Source: Cell Host and Microbe - May 27, 2020 Category: Microbiology Authors: Sun SH, Chen Q, Gu HJ, Yang G, Wang YX, Huang XY, Liu SS, Zhang NN, Li XF, Xiong R, Guo Y, Deng YQ, Huang WJ, Liu Q, Liu QM, Shen YL, Zhou Y, Yang X, Zhao TY, Fan CF, Zhou YS, Qin CF, Wang YC Tags: Cell Host Microbe Source Type: research

Type I and Type III Interferons - Induction, Signaling, Evasion, and Application to Combat COVID-19.
Abstract Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Without approved antiviral therapeutics or vaccines to this ongoing global threat, type I and type III interferons (IFNs) are currently being evaluated for their efficacy. Both the role of IFNs and the use of recombinant IFNs in two related, highly pathogenic coronaviruses, SARS-CoV and MERS-CoV, have been controversial in terms of their protective effects in the host. In this review, we describe the recent progress in our understanding of both type I and type III IFN-mediated i...
Source: Cell Host and Microbe - May 27, 2020 Category: Microbiology Authors: Park A, Iwasaki A Tags: Cell Host Microbe Source Type: research

The Innate Immune System: Fighting on the Front Lines or Fanning the Flames of COVID-19?
Abstract The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has had devastating global impacts and will continue to have dramatic effects on public health for years to come. A better understanding of the immune response to SARS-CoV-2 will be critical for the application and development of therapeutics. The degree to which the innate immune response confers protection or induces pathogenesis through a dysregulated immune response remains unclear. In this review, we discuss what is known about the role of the innate immune system during SARS-CoV-2 infection, suggest directions for future studies, ...
Source: Cell Host and Microbe - May 20, 2020 Category: Microbiology Authors: McKechnie JL, Blish CA Tags: Cell Host Microbe Source Type: research

Inducible Germline IgMs Bridge Trypanosome Lytic Factor Assembly and Parasite Recognition.
Abstract Trypanosomiasis is a devastating neglected tropical disease affecting livestock and humans. Humans are susceptible to two Trypanosoma brucei subspecies but protected from other trypanosomes by circulating high-density lipoprotein (HDL) complexes called trypanosome lytic factors (TLFs) 1 and 2. TLFs contain apolipoprotein L-1 contributing to lysis and haptoglobin-related protein (HPR), which can function as a ligand for a parasite receptor. TLF2 also uniquely contains non-covalently associated immunoglobin M (IgM) antibodies, the role and origin of which remain unclear. Here, we show that these TLF2-associ...
Source: Cell Host and Microbe - May 14, 2020 Category: Microbiology Authors: Verdi J, Zipkin R, Hillman E, Gertsch RA, Pangburn SJ, Thomson R, Papavasiliou N, Sternberg J, Raper J Tags: Cell Host Microbe Source Type: research

Favorable anakinra responses in severe covid-19 patients with secondary hemophagocytic lymphohistiocytosis.
FAVORABLE ANAKINRA RESPONSES IN SEVERE COVID-19 PATIENTS WITH SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS. Cell Host Microbe. 2020 May 14;: Authors: Dimopoulos G, de Mast Q, Markou N, Theodorakopoulou M, Komnos A, Mouktaroudi M, Netea MG, Spyridopoulos T, Verheggen RJ, Hoogerwerf J, Lachana A, van de Veerdonk FL, Giamarellos-Bourboulis EJ Abstract Dysregulation of inflammation is hypothesized to play a crucial role in the severe complications of COVID-19, with IL-1/IL-6 pathway being central. Here, we report on the treatment of eight severe COVID-19 pneumonia patients-- seven hospitalized in intensiv...
Source: Cell Host and Microbe - May 14, 2020 Category: Microbiology Authors: Dimopoulos G, de Mast Q, Markou N, Theodorakopoulou M, Komnos A, Mouktaroudi M, Netea MG, Spyridopoulos T, Verheggen RJ, Hoogerwerf J, Lachana A, van de Veerdonk FL, Giamarellos-Bourboulis EJ Tags: Cell Host Microbe Source Type: research

Finding Their Type: Elusive Antigenic Sites on Dengue Virus 3 Mapped with Human Antibodies.
Abstract In this issue of Cell Host & Microbe, Young et al. shed light on dengue virus 3-specific epitopes. Mapping of human monoclonal antibodies led to the discovery of six quaternary antigenic sites with strong neutralizing activity suggesting that epitopes involved with protective immunity may be more complex than previously realized. PMID: 32407701 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - May 13, 2020 Category: Microbiology Authors: Sarathy VV, Barrett ADT Tags: Cell Host Microbe Source Type: research

The Null Hypothesis of IFN- γ and Monocyte Function in Leishmaniasis.
The Null Hypothesis of IFN-γ and Monocyte Function in Leishmaniasis. Cell Host Microbe. 2020 May 13;27(5):683-684 Authors: Sacks DL Abstract The phagosomal pathogen Leishmania appears unaffected by deliberate changes in the early Th1/Th2 balance. In this issue, Carneiro et al. explain these paradoxical results by showing that manipulations affecting IFN-γ-mediated phagocyte activation are counteracted by effects on IFN-γ-dependent recruitment of CCR2+ monocytes permissive to parasite growth. PMID: 32407702 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - May 13, 2020 Category: Microbiology Authors: Sacks DL Tags: Cell Host Microbe Source Type: research

Hold It Right There! Gonococci Preserve Epithelium Integrity during Intimate Adherence.
Abstract Exfoliation is used as a mechanism to remove bacterially infected cells from the body. In this issue of Cell Host & Microbe, Muenzner and Hauck (2020) find that Neisseria gonorrhoeae blocks exfoliation by producing nitric oxide at the bacterial-host cell interface to promote tissue integrity. Uropathogenic Escherichia coli stimulates the same pathway, suggesting a common mechanism among bacterial pathogens. PMID: 32407703 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - May 13, 2020 Category: Microbiology Authors: Dillard JP Tags: Cell Host Microbe Source Type: research

When Lab Mice Go Wild, Fungi Are in Play.
Abstract In this issue of Cell Host & Microbe, Yeung et al. (2020) and Lin et al. (2020) expose laboratory mice to a natural environment and use immune and microbiota characterization to show that fungi promote more human-like immunity. These studies will help develop animal models to more accurately resemble human immune responses. PMID: 32407704 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - May 13, 2020 Category: Microbiology Authors: Wu M, Kasper DL Tags: Cell Host Microbe Source Type: research

Candida in IBD: Friend or Foe?
Abstract In this issue of Cell Host & Microbe, Leonardi et al. demonstrate ulcerative colitis patients with high Candida responded best to fecal microbial transplant (FMT). However, decreased Candida post-treatment was associated with improved disease-suggesting that Candida reductions are associated with less inflammation. Pre-FMT Candida levels may identify FMT responders. PMID: 32407705 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - May 13, 2020 Category: Microbiology Authors: Fritsch J, Abreu MT Tags: Cell Host Microbe Source Type: research

SARS-CoV-2: A New Song Recalls an Old Melody.
Abstract The viruses causing the SARS outbreak of 2002-2003 and current COVID-19 pandemic are related betacoronaviruses. What insights were learned from SARS that can inform SARS-CoV-2 vaccine development? Focusing on important lessons from SARS vaccine development and two SARS vaccines evaluated in humans may guide SARS-CoV-2 vaccine design, testing, and implementation. PMID: 32407706 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - May 13, 2020 Category: Microbiology Authors: Subbarao K Tags: Cell Host Microbe Source Type: research

Rational Vaccine Design in the Time of COVID-19.
Abstract As scientists consider SARS-CoV-2 vaccine design, we discuss problems that may be encountered and how to tackle them by what we term "rational vaccine design." We further discuss approaches to pan-coronavirus vaccines. We draw on experiences from recent research on several viruses including HIV and influenza, as well as coronaviruses. PMID: 32407707 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - May 13, 2020 Category: Microbiology Authors: Burton DR, Walker LM Tags: Cell Host Microbe Source Type: research

The Challenges of Vaccine Development against a New Virus during a Pandemic.
We describe the unique challenges of developing a vaccine against SARS-CoV-2 in a pandemic setting. PMID: 32407708 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - May 13, 2020 Category: Microbiology Authors: Diamond MS, Pierson TC Tags: Cell Host Microbe Source Type: research

Identification of Dengue Virus Serotype 3 Specific Antigenic Sites Targeted by Neutralizing Human Antibodies.
Harris E, Crowe JE, Baric RS Abstract The rational design of dengue virus (DENV) vaccines requires a detailed understanding of the molecular basis for antibody-mediated immunity. The durably protective antibody response to DENV after primary infection is serotype specific. However, there is an incomplete understanding of the antigenic determinants for DENV type-specific (TS) antibodies, especially for DENV serotype 3, which has only one well-studied, strongly neutralizing human monoclonal antibody (mAb). Here, we investigated the human B cell response in children after natural DENV infection in the endemic area of...
Source: Cell Host and Microbe - May 13, 2020 Category: Microbiology Authors: Young E, Carnahan RH, Andrade DV, Kose N, Nargi RS, Fritch EJ, Munt JE, Doyle MP, White L, Baric TJ, Stoops M, DeSilva A, Tse LV, Martinez DR, Zhu D, Metz S, Wong MP, Espinosa DA, Montoya M, Biering SB, Sukulpolvi-Petty S, Kuan G, Balmaseda A, Diamond MS, Tags: Cell Host Microbe Source Type: research

Identification of Human Single-Domain Antibodies against SARS-CoV-2.
We describe the development of a phage-displayed single-domain antibody library by grafting naive complementarity-determining regions (CDRs) into framework regions of a human germline immunoglobulin heavy chain variable region (IGHV) allele. Panning this library against SARS-CoV-2 RBD and S1 subunit identified fully human single-domain antibodies targeting five distinct epitopes on SARS-CoV-2 RBD with subnanomolar to low nanomolar affinities. Some of these antibodies neutralize SARS-CoV-2 by targeting a cryptic epitope located in the spike trimeric interface. Collectively, this work presents a versatile platform for rapid ...
Source: Cell Host and Microbe - May 12, 2020 Category: Microbiology Authors: Wu Y, Li C, Xia S, Tian X, Kong Y, Wang Z, Gu C, Zhang R, Tu C, Xie Y, Yang Z, Lu L, Jiang S, Ying T Tags: Cell Host Microbe Source Type: research

A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice.
s JA, de Koning-Ward T, Barry AE, Barchet W, Cockburn IA, McFadden GI, Gras S, Lahoud MH, Bertolino P, Schittenhelm RB, Caminschi I, Heath WR, Fernandez-Ruiz D Abstract Liver-resident memory CD8+ T (TRM) cells remain in and constantly patrol the liver to elicit rapid immunity upon antigen encounter and can mediate efficient protection against liver-stage Plasmodium infection. This finding has prompted the development of immunization strategies where T cells are activated in the spleen and then trapped in the liver to form TRM cells. Here, we identify PbRPL6120-127, a H2-Kb-restricted epitope from the putative...
Source: Cell Host and Microbe - May 6, 2020 Category: Microbiology Authors: Valencia-Hernandez AM, Ng WY, Ghazanfari N, Ghilas S, de Menezes MN, Holz LE, Huang C, English K, Naung M, Tan PS, Tullett KM, Steiner TM, Enders MH, Beattie L, Chua YC, Jones CM, Cozijnsen A, Mollard V, Cai Y, Bowen DG, Purcell AW, La Gruta NL, Villadang Tags: Cell Host Microbe Source Type: research

Salmonella Typhoid Toxin PltB Subunit and Its Non-typhoidal Salmonella Ortholog Confer Differential Host Adaptation and Virulence.
Abstract Typhoidal and non-typhoidal Salmonelleae (NTS) cause typhoid fever and gastroenteritis, respectively, in humans. Salmonella typhoid toxin contributes to typhoid disease progression and chronic infection, but little is known about the role of its NTS ortholog. We found that typhoid toxin and its NTS ortholog induce different clinical presentations. The PltB subunit of each toxin exhibits different glycan-binding preferences that correlate with glycan expression profiles of host cells targeted by each bacterium at the primary infection or intoxication sites. Through co-crystal structures of PltB subunits bo...
Source: Cell Host and Microbe - May 5, 2020 Category: Microbiology Authors: Lee S, Yang YA, Milano SK, Nguyen T, Ahn C, Sim JH, Thompson AJ, Hillpot EC, Yoo G, Paulson JC, Song J Tags: Cell Host Microbe Source Type: research

A Dynamic Immune Response Shapes COVID-19 Progression.
Abstract The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pat...
Source: Cell Host and Microbe - April 30, 2020 Category: Microbiology Authors: Ong EZ, Chan YFZ, Leong WY, Lee NMY, Kalimuddin S, Haja Mohideen SM, Chan KS, Tan AT, Bertoletti A, Ooi EE, Low JGH Tags: Cell Host Microbe Source Type: research

A Genomic Toolkit for the Mechanistic Dissection of Intractable Human Gut Bacteria.
We report a comparative genomics platform for Eggerthella lenta and other Coriobacteriia, a neglected taxon broadly relevant to human health and disease. We uncover extensive genetic and metabolic diversity and validate a tool for mapping phenotypes to genes and sequence variants. We also present a tool for the quantification of strains from metagenomic sequencing data, enabling the identification of genes that predict bacterial fitness. Competitive growth is reproducible under laboratory conditions and attributable to intrinsic growth rates and resource utilization. Unique signatures of in vivo competition in gn...
Source: Cell Host and Microbe - April 22, 2020 Category: Microbiology Authors: Bisanz JE, Soto-Perez P, Noecker C, Aksenov AA, Lam KN, Kenney GE, Bess EN, Haiser HJ, Kyaw TS, Yu FB, Rekdal VM, Ha CWY, Devkota S, Balskus EP, Dorrestein PC, Allen-Vercoe E, Turnbaugh PJ Tags: Cell Host Microbe Source Type: research

Combined Prebiotic and Microbial Intervention Improves Oral Cholera Vaccination Responses in a Mouse Model of Childhood Undernutrition.
Abstract Undernourished children in low-income countries often exhibit poor responses to oral vaccination. Perturbed microbiota development is linked to undernutrition, but whether and how microbiota changes affect vaccine responsiveness remains unclear. Here, we show that gnotobiotic mice colonized with microbiota from undernourished Bangladeshi children and fed a Bangladeshi diet exhibited microbiota-dependent differences in mucosal IgA responses to oral vaccination with cholera toxin (CT). Supplementation with a nutraceutical consisting of spirulina, amaranth, flaxseed, and micronutrients augmented CT-IgA produ...
Source: Cell Host and Microbe - April 22, 2020 Category: Microbiology Authors: Di Luccia B, Ahern PP, Griffin NW, Cheng J, Guruge JL, Byrne AE, Rodionov DA, Leyn SA, Osterman AL, Ahmed T, Colonna M, Barratt MJ, Delahaye NF, Gordon JI Tags: Cell Host Microbe Source Type: research

Critical Anti-CRISPR Locus Repression by a Bi-functional Cas9 Inhibitor.
Abstract Bacteriophages must rapidly deploy anti-CRISPR proteins (Acrs) to inactivate the RNA-guided nucleases that enforce CRISPR-Cas adaptive immunity in their bacterial hosts. Listeria monocytogenes temperate phages encode up to three anti-Cas9 proteins, with acrIIA1 always present. AcrIIA1 binds and inhibits Cas9 with its C-terminal domain; however, the function of its highly conserved N-terminal domain (NTD) is unknown. Here, we report that the AcrIIA1NTD is a critical transcriptional repressor of the strong anti-CRISPR promoter. A rapid burst of anti-CRISPR transcription occurs during phage infection and the...
Source: Cell Host and Microbe - April 21, 2020 Category: Microbiology Authors: Osuna BA, Karambelkar S, Mahendra C, Sarbach A, Johnson MC, Kilcher S, Bondy-Denomy J Tags: Cell Host Microbe Source Type: research

Listeria Phages Induce Cas9 Degradation to Protect Lysogenic Genomes.
Abstract Bacterial CRISPR-Cas systems employ RNA-guided nucleases to destroy phage (viral) DNA. Phages, in turn, have evolved diverse "anti-CRISPR" proteins (Acrs) to counteract acquired immunity. In Listeria monocytogenes, prophages encode two to three distinct anti-Cas9 proteins, with acrIIA1 always present. However, the significance of AcrIIA1's pervasiveness and its mechanism are unknown. Here, we report that AcrIIA1 binds with high affinity to Cas9 via the catalytic HNH domain. During lysogeny in Listeria, AcrIIA1 triggers Cas9 degradation. During lytic infection, however, AcrIIA1 fails to block Cas...
Source: Cell Host and Microbe - April 18, 2020 Category: Microbiology Authors: Osuna BA, Karambelkar S, Mahendra C, Christie KA, Garcia B, Davidson AR, Kleinstiver BP, Kilcher S, Bondy-Denomy J Tags: Cell Host Microbe Source Type: research

Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure.
i K, Lekakis V, Lupse M, Kotsaki A, Renieris G, Theodoulou D, Panou V, Koukaki E, Koulouris N, Gogos C, Koutsoukou A Abstract Proper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7-8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompa...
Source: Cell Host and Microbe - April 17, 2020 Category: Microbiology Authors: Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, Damoraki G, Gkavogianni T, Adami ME, Katsaounou P, Ntaganou M, Kyriakopoulou M, Dimopoulos G, Koutsodimitropoulos I, Velissaris D, Koufargyris P, Karageorgos A, Katri Tags: Cell Host Microbe Source Type: research

VSV-Displayed HIV-1 Envelope Identifies Broadly Neutralizing Antibodies Class-Switched to IgG and IgA.
Abstract The HIV-1 envelope (Env) undergoes conformational changes during infection. Broadly neutralizing antibodies (bNAbs) are typically isolated by using soluble Env trimers, which do not capture all Env states. To address these limitations, we devised a vesicular stomatitis virus (VSV)-based probe to display membrane-embedded Env trimers and isolated five bNAbs from two chronically infected donors, M4008 and M1214. Donor B cell receptor (BCR) repertoires identified two bNAb lineages, M4008_N1 and M1214_N1, that class-switched to immunoglobulin G (IgG) and IgA. Variants of these bNAbs reconstituted as IgA demon...
Source: Cell Host and Microbe - April 15, 2020 Category: Microbiology Authors: Jia M, Liberatore RA, Guo Y, Chan KW, Pan R, Lu H, Waltari E, Mittler E, Chandran K, Finzi A, Kaufmann DE, Seaman MS, Ho DD, Shapiro L, Sheng Z, Kong XP, Bieniasz PD, Wu X Tags: Cell Host Microbe Source Type: research

Th1-Th2 Cross-Regulation Controls Early Leishmania Infection in the Skin by Modulating the Size of the Permissive Monocytic Host Cell Reservoir.
We report that prior to influencing activation, Th1/Th2 immunity first controls the size of the permissive host cell reservoir. During early Leishmania infection of the skin, IFN-γ- or STAT6-mediated changes in phagocyte activation were counteracted by changes in IFN-γ-mediated recruitment of permissive CCR2+ monocytes. Monocytes were required for early parasite expansion and acquired an alternatively activated phenotype despite the Th1 dermal environment required for their recruitment. Surprisingly, STAT6 did not enhance intracellular parasite proliferation, but rather modulated the size and permissi...
Source: Cell Host and Microbe - April 13, 2020 Category: Microbiology Authors: Carneiro MB, Lopes ME, Hohman LS, Romano A, David BA, Kratofil R, Kubes P, Workentine ML, Campos AC, Vieira LQ, Peters NC Tags: Cell Host Microbe Source Type: research

Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins.
Abstract Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors. Additionally, human-adapted HAs gain glycosylation sites over time, although their biological function is poorly defined. Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain. By contrast, poorly adapted avian-origin HAs contain predominately complex-type glycans, which have ...
Source: Cell Host and Microbe - April 10, 2020 Category: Microbiology Authors: Thompson AJ, Cao L, Ma Y, Wang X, Diedrich JK, Kikuchi C, Willis S, Worth C, McBride R, Yates JR, Paulson JC Tags: Cell Host Microbe Source Type: research

Neisseria gonorrhoeae Blocks Epithelial Exfoliation by Nitric-Oxide-Mediated Metabolic Cross Talk to Promote Colonization in Mice.
Abstract Several pathogens suppress exfoliation, a key defense of epithelia against microbial colonization. Common among these pathogens, exemplified by Neisseria gonorrhoeae, is their ability to bind carcinoembryonic antigen-related cell adhesion molecules (CEACAMs). Gonococcal CEACAM engagement triggers the expression of CD105, which is necessary to block epithelial exfoliation, whereas homotypic CEACAM-CEACAM interactions or antibody-mediated CEACAM clustering does not lead to CD105 expression. Here, we show that CEACAM-associated bacteria release nitric oxide (NO) during anaerobic respiration, and membrane-per...
Source: Cell Host and Microbe - April 10, 2020 Category: Microbiology Authors: Muenzner P, Hauck CR Tags: Cell Host Microbe Source Type: research

An Infectious cDNA Clone of SARS-CoV-2.
We report a reverse genetic system for SARS-CoV-2. Seven complimentary DNA (cDNA) fragments spanning the SARS-CoV-2 genome were assembled into a full-genome cDNA. RNA transcribed from the full-genome cDNA was highly infectious after electroporation into cells, producing 2.9 × 106 plaque-forming unit (PFU)/mL of virus. Compared with a clinical isolate, the infectious-clone-derived SARS-CoV-2 (icSARS-CoV-2) exhibited similar plaque morphology, viral RNA profile, and replication kinetics. Additionally, icSARS-CoV-2 retained engineered molecular markers and did not acquire other mutations. We generated a stable mNeo...
Source: Cell Host and Microbe - April 9, 2020 Category: Microbiology Authors: Xie X, Muruato A, Lokugamage KG, Narayanan K, Zhang X, Zou J, Liu J, Schindewolf C, Bopp NE, Aguilar PV, Plante KS, Weaver SC, Makino S, LeDuc JW, Menachery VD, Shi PY Tags: Cell Host Microbe Source Type: research

HIV-1 Broadly Neutralizing Antibodies Take the Road Less Traveled, and That Makes All the Difference.
Abstract Broadly neutralizing antibodies (bnAbs) against HIV-1 provide critical insights into co-evolution between the virus and human B cell responses. In this issue of Cell Host & Microbe, Shen et al. (2020) describe a rare mutation in an antibody lineage targeting the fusion peptide of HIV-1 envelope creating a critical bifurcation, with only one path leading to bnAb development. PMID: 32272069 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - April 8, 2020 Category: Microbiology Authors: Roskin K, Spearman P Tags: Cell Host Microbe Source Type: research

Caging and COM-Bating Antibiotic Resistance.
Abstract Horizontal gene transfer (HGT) facilitates spead of antibiotic resistance elements. In this issue of Cell Host & Microbe, Domenech et al. discover that compounds disrupting proton motive force block natural competence (COM) and interrupt intraspecies HGT and exchange of antibiotic resistance. Such strategies might minimize clinical spread of antibiotic resistance. PMID: 32272070 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - April 8, 2020 Category: Microbiology Authors: Rosch JW, Tuomanen EI Tags: Cell Host Microbe Source Type: research

Taking the STING Out of Sepsis?
Abstract In this issue of Cell Host & Microbe, Zhang et al. use a sepsis mouse model to show that macrophage-specific release of coagulation factor F3 depends on pathogen detection and responses mediated by TMEM173/STING. The therapeutic power of targeting TMEM173/STING-F3 is evident in mice, but will it penetrate the sepsis bedside? PMID: 32272071 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - April 8, 2020 Category: Microbiology Authors: Vandewalle J, Vanderhaeghen T, Beyaert R, Libert C Tags: Cell Host Microbe Source Type: research

A Vibriophage Takes Antirepression to the Next Level.
Abstract Since its isolation by Esther Lederberg, phage lambda and its repressor protein CI have contributed substantially to the advancement of molecular biology. In this issue of Cell Host & Microbe, Silpe et al. (2020) characterize the antirepressor Qtip of Vibrio phage VP882, which through CI sequestration triggers a lytic switch. PMID: 32272072 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - April 8, 2020 Category: Microbiology Authors: Lemos Rocha LF, Blokesch M Tags: Cell Host Microbe Source Type: research

Targeting Plasmepsins-An Achilles' Heel of the Malaria Parasite.
Abstract Recently, two Plasmodium aspartyl proteases were identified as druggable targets impacting parasite survival. In this issue of Cell Host & Microbe, Favuzza et al. describe the optimization of a compound series acting on both targets, heralding the prospect of a new class of antimalarials for clinical studies. PMID: 32272073 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - April 8, 2020 Category: Microbiology Authors: Burrows JN, Soldati-Favre D Tags: Cell Host Microbe Source Type: research

HIV/AIDS Research for the Future.
Abstract Despite significant progress, several questions related to HIV infection remain to be addressed. Here, I provide my perspective on four key areas that need further research to inform curative and preventive measures against HIV/AIDS. PMID: 32272074 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - April 8, 2020 Category: Microbiology Authors: Gallo RC Tags: Cell Host Microbe Source Type: research

PrEP for HIV Prevention: Evidence, Global Scale-up, and Emerging Options.
Abstract Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV infection was demonstrated to be efficacious and safe earlier this decade from pivotal studies using oral emtricitabine-tenofovir disoproxil fumarate. Regulatory approval and normative guidance, now for almost 70 countries worldwide, has followed. Demonstration projects have shown high uptake and population-level HIV reductions, highlighting the need for simplifying delivery and reducing current barriers to access and persistence. A portfolio of additional, next-generation PrEP formulations, currently under testing, if effective, wil...
Source: Cell Host and Microbe - April 8, 2020 Category: Microbiology Authors: Celum C, Baeten J Tags: Cell Host Microbe Source Type: research

Env Exceptionalism: Why Are HIV-1 Env Glycoproteins Atypical Immunogens?
Abstract Recombinant HIV-1 envelope (Env) glycoproteins of ever-increasing sophistication have been evaluated as vaccine candidates for over 30 years. Structurally defined mimics of native trimeric Env glycoproteins (e.g., SOSIP trimers) present multiple epitopes for broadly neutralizing antibodies (bNAbs) and their germline precursors, but elicitation of bNAbs remains elusive. Here, we argue that the interactions between Env and the immune system render it exceptional among viral vaccine antigens and hinder its immunogenicity in absolute and comparative terms. In other words, Env binds to CD4 on key immune cells ...
Source: Cell Host and Microbe - April 8, 2020 Category: Microbiology Authors: Klasse PJ, Ozorowski G, Sanders RW, Moore JP Tags: Cell Host Microbe Source Type: research