bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endogenous IL-27 during toxoplasmosis limits early monocyte responses and their inflammatory activation by pathological T cells
Authors: Aldridge Daniel L. , Moodley Devapregasan , Park Jeongho , Phan Anthony T. , Rausch Matthew , White Kerry F. , Ren Yue , Golin Karin , Radaelli Enrico , Kedl Ross , Holland Pamela M. , Hill Jonathan , Hunter Christopher A. 
Published: February 2024

ABSTRACT

Mice that lack the genes for IL-27, or the IL-27 receptor, and infected with
Toxoplasma gondii
develop T cell-mediated pathology. Here, studies were performed to determine the impact of endogenous IL-27 on the immune response to
T. gondii
in wild-type (WT) mice. Analysis of infected mice revealed the early production of IL-27p28 by a subset of Ly6C
hi
, inflammatory monocytes, and sustained IL-27p28 production at sites of acute and chronic infection. Administration of anti-IL-27p28 prior to infection resulted in an early (day 5) increase in levels of macrophage and granulocyte activation, as well as enhanced effector T cell responses, as measured by both cellularity, cytokine production, and transcriptional profiling. This enhanced acute response led to immune pathology, while blockade during the chronic phase of infection resulted in enhanced T cell responses but no systemic pathology. In the absence of IL-27, the enhanced monocyte responses observed at day 10 were a secondary consequence of activated CD4
+
T cells. Thus, in WT mice, IL-27 has distinct suppressive effects that impact innate and adaptive immunity during different phases of this infection.

IMPORTANCE

The molecule IL-27 is critical in limiting the immune response to the parasite
Toxoplasma gondii
. In the absence of IL-27, a lethal, overactive immune response develops during infection. However, when exactly in the course of infection this molecule is needed was unclear. By selectively inhibiting IL-27 during this parasitic infection, we discovered that IL-27 was only needed during, but not prior to, infection. Additionally, IL-27 is only needed in the active areas in which the parasite is replicating. Finally, our work found that a previously unstudied cell type, monocytes, was regulated by IL-27, which contributes further to our understanding of the regulatory networks established by this molecule.
Inter-species interactions between two bacterial flower commensals and a floral pathogen reduce disease incidence and alter pathogen activity
Authors: Hassani M. Amine , Cui Zhouqi , LaReau Jacquelyn , Huntley Regan B. , Steven Blaire , Zeng Quan 
Published: February 2024

ABSTRACT

Flowers are colonized by a diverse community of microorganisms that can alter plant health and interact with floral pathogens.
Erwinia amylovora
is a flower-inhabiting bacterium and a pathogen that infects different plant species, including
Malus × domestica
(apple). Previously, we showed that the co-inoculation of two bacterial strains, members of the genera
Pseudomonas
and
Pantoea,
isolated from apple flowers, reduced disease incidence caused by this floral pathogen. Here, we decipher the ecological interactions between the two flower-associated bacteria and
E. amylovora
in field experimentation and
in vitro
co-cultures. The two flower commensal strains did not competitively exclude
E. amylovora
from the stigma habitat, as both bacteria and the pathogen co-existed on the stigma of apple flowers and
in vitro
. This suggests that plant protection might be mediated by other mechanisms than competitive niche exclusion. Using a synthetic stigma exudation medium, ternary co-culture of the bacterial strains led to a substantial alteration of gene expression in both the pathogen and the two microbiota members. Importantly, the gene expression profiles for the ternary co-culture were not just additive from binary co-cultures, suggesting that some functions only emerged in multipartite co-culture. Additionally, the ternary co-culture of the strains resulted in a stronger acidification of the growth milieu than mono- or binary co-cultures, pointing to another emergent property of co-inoculation. Our study emphasizes the critical role of emergent properties mediated by inter-species interactions within the plant holobiont and their potential impact on plant health and pathogen behavior.

IMPORTANCE

Fire blight, caused by
Erwinia amylovora
, is one of the most important plant diseases of pome fruits. Previous work largely suggested plant microbiota commensals suppressed disease by antagonizing pathogen growth. However, inter-species interactions of multiple flower commensals and their influence on pathogen activity and behavior have not been well studied. Here, we show that co-inoculating two bacterial strains that naturally colonize the apple flowers reduces disease incidence. We further demonstrate that the interactions between these two microbiota commensals and the floral pathogen led to the emergence of new gene expression patterns and a strong alteration of the external pH, factors that may modify the pathogen’s behavior. Our findings emphasize the critical role of emergent properties mediated by inter-species interactions between plant microbiota and plant pathogens and their impact on plant health.
Bacteroides thetaiotaomicron
metabolic activity decreases with polysaccharide molecular weight
Authors: Wong Jeremy P. H. , Chillier Noémie , Fischer-Stettler Michaela , Zeeman Samuel C. , Battin Tom J. , Persat Alexandre 
Published: February 2024

ABSTRACT

The human colon hosts hundreds of commensal bacterial species, many of which ferment complex dietary carbohydrates. To transform these fibers into metabolically accessible compounds, microbes often express a series of dedicated enzymes homologous to the starch utilization system (Sus) encoded in polysaccharide utilization loci (PULs). The genome of
Bacteroides thetaiotaomicron
(
Bt
), a common member of the human gut microbiota, encodes nearly 100 PULs, conferring a strong metabolic versatility. While the structures and functions of individual enzymes within the PULs have been investigated, little is known about how polysaccharide complexity impacts the function of Sus-like systems. We here show that the activity of Sus-like systems depends on polysaccharide size, ultimately impacting bacterial growth. We demonstrate the effect of size-dependent metabolism in the context of dextran metabolism driven by the specific utilization system PUL48. We find that as the molecular weight of dextran increases,
Bt
growth rate decreases and lag time increases. At the enzymatic level, the dextranase BT3087, a glycoside hydrolase (GH) belonging to the GH family 66, is the main GH for dextran utilization, and BT3087 and BT3088 contribute to
Bt
dextran metabolism in a size-dependent manner. Finally, we show that the polysaccharide size-dependent metabolism of
Bt
impacts its metabolic output in a way that modulates the composition of a producer-consumer community it forms with
Bacteroides fragilis
. Altogether, our results expose an overlooked aspect of
Bt
metabolism that can impact the composition and diversity of microbiota.

IMPORTANCE

Polysaccharides are complex molecules that are commonly found in our diet. While humans lack the ability to degrade many polysaccharides, their intestinal microbiota contain bacterial commensals that are versatile polysaccharide utilizers. The gut commensal
Bacteroides thetaiotaomicron
dedicates roughly 20% of their genomes to the expression of polysaccharide utilization loci for the broad range utilization of polysaccharides. Although it is known that different polysaccharide utilization loci are dedicated to the degradation of specific polysaccharides with unique glycosidic linkages and monosaccharide compositions, it is often overlooked that specific polysaccharides may also exist in various molecular weights. These different physical attributes may impact their processability by starch utilization system-like systems, leading to differing growth rates and nutrient-sharing properties at the community level. Therefore, understanding how molecular weight impacts utilization by gut microbe may lead to the potential design of novel precision prebiotics.
Unraveling the crystal structure of the HpaA adhesin: insights into cell adhesion function and epitope localization of a
Helicobacter pylori
vaccine candidate
Authors: Martini Cyrielle , Araba Victoria , Beniani Meriem , Armoa Ortiz Paula , Simmons Mimi , Chalbi Mariem , Mellouk Abdelkader , El Bakkouri Majida , Calmettes Charles 
Published: February 2024

ABSTRACT

Helicobacter pylori
is a bacterium that exhibits strict host restriction to humans and non-human primates, and the bacterium is widely acknowledged as a significant etiological factor in the development of chronic gastritis, peptic ulcers, and gastric cancers. The pathogenic potential of this organism lies in its adeptness at colonizing the gastric mucosa, which is facilitated by a diverse repertoire of virulence factors, including adhesins that promote the attachment of the bacteria to the gastric epithelium. Among these adhesins, HpaA stands out due to its conserved nature and pivotal role in establishing
H. pylori
colonization. Moreover, this lipoprotein holds promise as an antigen for the development of effective
H. pylori
vaccines, thus attracting considerable attention for in-depth investigations into its molecular function and identification of binding determinants. Here, we present the elucidation of the crystallographic structure of HpaA at 2.9 Å resolution. The folding adopts an elongated protein shape, which is distinctive to the
Helicobacteraceae
family, and features an apical domain extension that plays a critical role in the cell-adhesion activity on gastric epithelial cells. Our study also demonstrates the ability of HpaA to induce TNF-α expression in macrophages, highlighting a novel role as an immunoregulatory effector promoting the pro-inflammatory response
in vitro
. These findings not only contribute to a deeper comprehension of the multifaceted role of HpaA in
H. pylori
pathogenesis but also establish a fundamental basis for the design and development of structure-based derivatives, aimed at enhancing the efficacy of
H. pylori
vaccines.

IMPORTANCE

Helicobacter pylori
is a bacterium that can cause chronic gastritis, peptic ulcers, and gastric cancers. The bacterium adheres to the lining of the stomach using proteins called adhesins. One of these proteins, HpaA, is particularly important for
H. pylori
colonization and is considered a promising vaccine candidate against
H. pylori
infections. In this work, we determined the atomic structure of HpaA, identifying a characteristic protein fold to the
Helicobacter
family and delineating specific amino acids that are crucial to support the attachment to the gastric cells. Additionally, we discovered that HpaA can trigger the production of TNF-α, a proinflammatory molecule, in macrophages. These findings provide valuable insights into how
H. pylori
causes disease and suggest that HpaA has a dual role in both attachment and immune activation. This knowledge could contribute to the development of improved vaccine strategies for preventing
H. pylori
infections.
Identification of a new export signal that targets early subunits to the flagellar type III secretion export machinery
Authors: Bryant Owain J. , Fraser Gillian M. 
Published: February 2024

ABSTRACT

Type III secretion systems (T3SSs) are essential for motility and virulence in many bacterial pathogens. Proteins destined for the flagellar T3SS contain at least two export signals in their N-terminal D
0
domain. Here, we describe a third carboxy (C)-terminal signal in early flagellar subunits that facilitates subunit targeting to the export machinery. Mutational analysis identified critical residues within the flagellar hook subunit C-terminal export signal. The flagellar ATPase and cytoplasmic ring components were not required for this targeting, indicating that core export machinery components facilitate substrate targeting via the C-terminal export signal. More broadly, these results demonstrate that multiple distinct export signals within type III secretion substrates facilitate distinct export events at the T3SS export machinery. Our data establish key events in the export mechanism of type III secretion systems: targeting of subunits to and their sequential interactions with key components of the export machinery.

IMPORTANCE
Many bacterial pathogens utilize T3SS to inject virulence proteins (effectors) into host cells or to assemble flagella on the bacterial cell surface. Bacterial flagella present a paradigm for how cells build and operate complex cell-surface “nanomachines.” Efficient subunit targeting from the bacterial cytosol to type III secretion systems is essential for rapid assembly and secretion by T3SSs. Subunits are thought to dock at the export machinery before being unfolded and translocated into the export channel. However, little is known about how subunits dock at the export machinery and the events that occur post docking. Here, we identified a new export signal within the C-termini of subunits that is essential for targeting of subunits to the type III export machinery. We show that this new export signal and previously identified export signals are recognized separately and sequentially, revealing a pathway for subunit transit through the type III export machinery in which sequential recognition events carry out different roles at major steps in the export pathway.
Host E3 ubiquitin ligase ITCH mediates
Toxoplasma gondii
effector GRA35-triggered NLRP1 inflammasome activation and cell-autonomous immunity
Authors: Wang Yifan , Hollingsworth L. Robert , Sangaré Lamba Omar , Paredes-Santos Tatiana C. , Krishnamurthy Shruthi , Penn Bennett H. , Wu Hao , Saeij Jeroen P. J. 
Published: February 2024

ABSTRACT

Toxoplasma gondii
is an intracellular parasite that can activate the NLRP1 inflammasome leading to macrophage pyroptosis in Lewis rats, but the underlying mechanism is not well understood. In this study, we performed a genome-wide CRISPR screen and identified the dense granule proteins GRA35, GRA42, and GRA43 as the
Toxoplasma
effectors mediating cell death in Lewis rat macrophages. GRA35 localizes on the parasitophorous vacuole membrane, where it interacts with the host E3 ubiquitin ligase ITCH. Inhibition of proteasome activity or ITCH knockout prevented pyroptosis in
Toxoplasma
-infected Lewis rat macrophages, consistent with the “NLRP1 functional degradation model.” However, there was no evidence that ITCH directly ubiquitinates or interacts with rat NLRP1. We also found that GRA35-ITCH interaction affected
Toxoplasma
fitness in IFNγ-activated human fibroblasts, likely due to ITCH’s role in recruiting ubiquitin and the parasite-restriction factor RNF213 to the parasitophorous vacuole membrane. These findings identify a new role of host E3 ubiquitin ligase ITCH in mediating effector-triggered immunity, a critical concept that involves recognizing intracellular pathogens and initiating host innate immune responses.

IMPORTANCE

Effector-triggered immunity represents an innate immune defense mechanism that plays a crucial role in sensing and controlling intracellular pathogen infection. The NLRP1 inflammasome in the Lewis rats can detect
Toxoplasma
infection, which triggers proptosis in infected macrophages and eliminates the parasite’s replication niche. The work reported here revealed that host E3 ubiquitin ligase ITCH is able to recognize and interact with
Toxoplasma
effector protein GRA35 localized on the parasite-host interface, leading to NLRP1 inflammasome activation in Lewis rat macrophages. Furthermore, ITCH-GRA35 interaction contributes to the restriction of
Toxoplasma
in human fibroblasts stimulated by IFNγ. Thus, this research provides valuable insights into understanding pathogen recognition and restriction mediated by host E3 ubiquitin ligase.
Activin A levels are raised during human tuberculosis and blockade of the activin signaling axis influences murine responses to
M. tuberculosis
infection
Authors: Nieuwenhuizen Natalie E. , Nouailles Geraldine , Sutherland Jayne S. , Zyla Joanna , Pasternack Arja H. , Heyckendorf Jan , Frye Björn C. , Höhne Kerstin , Zedler Ulrike , Bandermann Silke , Abu Abed Ulrike , Brinkmann Volker , Gutbier Birgitt , Witzenrath Martin , Suttorp Norbert , Zissel Gernot , Lange Christoph , Ritvos Olli , Kaufmann Stefan H. E. ,   the CAPNETZ Study group,   the DZIF TB study group
Published: February 2024

ABSTRACT

Activin A strongly influences immune responses; yet, few studies have examined its role in infectious diseases. We measured serum activin A levels in two independent tuberculosis (TB) patient cohorts and in patients with pneumonia and sarcoidosis. Serum activin A levels were increased in TB patients compared to healthy controls, including those with positive tuberculin skin tests, and paralleled severity of disease, assessed by X-ray scores. In pneumonia patients, serum activin A levels were also raised, but in sarcoidosis patients, levels were lower. To determine whether blockade of the activin A signaling axis could play a functional role in TB, we harnessed a soluble activin type IIB receptor fused to human IgG1 Fc, ActRIIB-Fc, as a ligand trap in a murine TB model. The administration of ActRIIB-Fc to
Mycobacterium tuberculosis
-infected mice resulted in decreased bacterial loads and increased numbers of CD4 effector T cells and tissue-resident memory T cells in the lung. Increased frequencies of tissue-resident memory T cells corresponded with downregulated T-bet expression in lung CD4 and CD8 T cells. Altogether, the results suggest a disease-exacerbating role of ActRIIB signaling pathways. Serum activin A may be useful as a biomarker for diagnostic triage of active TB or monitoring of anti-tuberculosis therapy.

IMPORTANCE

Tuberculosis remains the leading cause of death by a bacterial pathogen. The etiologic agent of tuberculosis,
Mycobacterium tuberculosis
, can remain dormant in the infected host for years before causing disease. Significant effort has been made to identify biomarkers that can discriminate between latently infected and actively diseased individuals. We found that serum levels of the cytokine activin A were associated with increased lung pathology and could discriminate between active tuberculosis and tuberculin skin-test-positive healthy controls. Activin A signals through the ActRIIB receptor, which can be blocked by administration of the ligand trap ActRIIB-Fc, a soluble activin type IIB receptor fused to human IgG1 Fc. In a murine model of tuberculosis, we found that ActRIIB-Fc treatment reduced mycobacterial loads. Strikingly, ActRIIB-Fc treatment significantly increased the number of tissue-resident memory T cells. These results suggest a role for ActRIIB signaling pathways in host responses to
Mycobacterium tuberculosis
and activin A as a biomarker of ongoing disease.
Genome sequence of bubaline herpesvirus-1 associated with pustular vulvovaginitis in Indian water buffalo
Authors: Yadav Sarita , Boora Ashok , Thomas Prasad , Kaliappan Abinaya , Verma Nisha , Devi Parvina , Dhaka Nishu , Khurana Sandip , Kumar Anil , Balhara Sunesh , Balhara Ashok , Lailer Puran Chand 
Published: February 2024

ABSTRACT

We report here the genome sequence of a bubaline herpesvirus 1 isolated from Indian water buffalo. The bubaline herpesvirus 1 strain S102_1 was isolated in 2021 from a Murrah buffalo heifer with clinical presentation of pustular vulvovaginitis.
Draft genome sequences of
Pseudomonas
strains zfem001–005 isolated from the intestine of larval zebrafish
Danio rerio
Authors: Simbassa Sabona B. , Clark Justin , Salazar Keiko , Maresso Anthony , Krachler Anne- Marie 
Published: February 2024

ABSTRACT

Here, we report the draft genome sequences of
Pseudomonas
strains zfem001–005, five isolates from the intestinal microbiota of healthy larval zebrafish
Danio rerio
at a developmental age of 7 days post fertilization. The isolates have been identified as
Pseudomonas sediminis
,
Pseudomonas japonica
,
Pseudomonas otitidis
,
Pseudomonas sichuanensis
, and
Pseudomonas tohonis
, respectively.
Draft genome sequences of
Arthrobacter
sp. AZCC_0090 and
Mycobacterium
sp. AZCC_0083 isolated from oligotrophic subsurface forest soil in the Santa Catalina mountains of Southern Arizona
Authors: Kridler Melanie R. , Viney Isabella A. , Custer Joy M. , Schlottman Bradley , Bartelme Ryan , Carini Paul 
Published: February 2024

ABSTRACT

Here, we present the genomes of two soil actinobacteria:
Arthrobacter
sp. strain AZCC_0090 and
Mycobacterium
sp. strain AZCC_0083, isolated from oligotrophic subsurface soils in Southern Arizona, USA.
Complete genome sequence of a nucleopolyhedrovirus isolated from
Bombyx mori
in Hakozaki, Japan, obtained using Oxford Nanopore Technologies sequencing
Authors: Tatsuke Tsuneyuki 
Published: February 2024

ABSTRACT

I report the complete genome sequence of an isolate of nucleopolyhedrovirus from
Bombyx mori
, the domesticated silkworm, maintained for the long term at Kyushu University in Hakozaki, Fukuoka Prefecture, Japan. The genome is 127,783 bp long, with a G+C content of 40.3%, and contains 142 open reading frames.
Genome sequence of bacteriophage Djungelskog isolated from an
Arthrobacter globiformis
culture
Authors: Oliveros Abigail M. , McDougall Shelby A. , Snyder Miles A. , Snowden Sara K. , Richard Joseph D. , Rao Christopher M. , Ponce Marybeth , Pitonza Christopher J. , Ozcelik Mira , Mannina Sofia S. , Magna Juliana R. , Lopez Andrew S. , Gustafson Linnea C. , Glackin Brynn K. , Dolge Abigail E. , DeLancy Nate D. , Davis Andrew B. C. , Davis Thomas P. , Blagodar Max , Natale Sydney N. , Dennis Megan K. , Godin Elizabeth A. 
Published: February 2024

ABSTRACT

Actinobacteriophage Djungelskog was isolated from a sample of degraded organic material in Poughkeepsie, NY, using
Arthrobacter globiformis B-2979
. Its genome is 54,512 bp and encodes 86 putative protein-coding genes. Djungelskog has a siphovirus morphology and is assigned to cluster AW based on gene content similarity to actinobacteriophages.