bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNF20 dual regulation of MDA5 signaling to maintain immune homeostasis in chickens
Authors: Wang Jie , Liu Qiuju , Zhang Kehui , Zhao Shurui , Shao Qi , Fu Feiyu , Ma Jingjiao , Wang Zhaofei , Yan Ya-xian , Wang Hengan , Sun Jianhe , Cheng Yuqiang 
Published: February 2025

ABSTRACT

RIG-I and MDA5, known as the RIG-I-like receptors (RLRs), play a pivotal role in inducing antiviral responses to RNA viral infections. While chickens lack RIG-I, they possess a functionally enhanced MDA5 that recognizes pathogens and regulates immunity, underscoring the critical role of MDA5 in maintaining immune homeostasis in chickens. However, the precise mechanisms governing the expression and optimal activation of MDA5 remain unclear. Here, we reveal that the chicken E3 ubiquitin ligase RNF20 is essential for modulating MDA5-mediated innate immune homeostasis. Transcriptome sequencing analysis revealed that RNA viral infection of DF-1 cells significantly upregulated the expression of chicken RNF20. Overexpression of RNF20 markedly suppresses the expression of chicken innate immunity-related genes, while RNF20 knockout leads to immune deficiency both
in vivo
and
in vitro
. Mechanistically, RNF20 is located in the nucleus, where it maintains the basic expression and regulates the inducible expression of MDA5 to establish immune defense during the early infection phase. In the late phase, RNF20 translocates to the cytoplasm, where it facilitates the K27- and K48-linked polyubiquitination and subsequent degradation of MDA5, thereby preventing immune overstimulation. Overall, this study establishes RNF20 as an important E3 ubiquitin ligase that maintains chicken innate immune homeostasis.

IMPORTANCE
Chicken MDA5 is an important RNA viral sensor for initiating the antiviral innate immune response. The protein level of MDA5 must be tightly regulated to maintain antiviral innate immune homeostasis. In this study, we demonstrate that the E3 ubiquitin ligase RNF20 precisely regulates MDA5 protein stabilization through nucleoplasmic translocation. Specifically, in uninfected and during early infection, RNF20 regulates MDA5 transcription in the nucleus. While in the late stages of infection, RNF20 translocates out of the nucleus and catalyzes the ubiquitinated degradation of MDA5. Thus, RNF20 is important in regulating chicken antiviral innate immune homeostasis.
Deployment of a
Vibrio cholerae
ordered transposon mutant library in a quorum-competent genetic background
Authors: Grant Nkrumah A. , Donkor Gracious Yoofi , Sontz Jordan , Soto William , Waters Christopher M. 
Published: February 2025

ABSTRACT

Vibrio cholerae
, the causative agent of cholera, has sparked seven pandemics in recent centuries, with the current one being the most prolonged.
V. cholerae’s
pathogenesis hinges on its ability to switch between low- and high-cell-density gene regulatory states, enabling transmission between the host and the environment. Previously, a transposon mutant library for
V. cholerae
was created to support investigations aimed toward uncovering the genetic determinants of its pathogenesis. However, subsequent sequencing uncovered a mutation in the gene
luxO
of the parent strain, rendering mutants unable to exhibit high-cell-density behaviors. In this study, we used chitin-independent natural transformation to move transposon insertions from these low-cell-density mutants into a wild-type genomic background. Library transfer was aided by a novel gDNA extraction method we developed using thymol, which also showed high lysis specificity for
Vibrio
. The resulting Grant Library comprises 3,102 unique transposon mutants, covering 79.8% of
V. cholerae’s
open reading frames. Whole-genome sequencing of randomly selected mutants demonstrates 100% precision in transposon transfer to cognate genomic positions of the recipient strain in every strain analyzed. Notably, in no instance did the
luxO
mutation transfer into the wild-type background. Our research uncovered density-dependent epistasis in growth on inosine, an immunomodulatory metabolite secreted by gut bacteria that is implicated in enhancing gut barrier functions. Additionally, Grant Library mutants retain the plasmid that enables rapid, scarless genomic editing. In summary, the Grant Library reintroduces organismal-relevant genetic contexts absent in the low-cell-density-locked library equivalent.

Ordered transposon mutant libraries are essential tools for catalyzing research by providing access to null mutants of all non-essential genes. Such a library was previously generated for
Vibrio cholerae
, but whole-genome sequencing revealed that this library was made using a parent strain that is unable to exhibit cell-cell communication known as quorum sensing. Here, we utilize natural competence combined with a novel, high-throughput genomic DNA extraction method to regenerate the signaling incompetent
V. cholerae
ordered transposon mutant library in quorum-sensing-competent strain. Our library provides researchers with a powerful tool to understand
V. cholerae
biology within a genetic context that influences how it transitions from an environmentally benign organism to a disease-causing pathogen.
Dual function of
Candida auris
mannosyltransferase, MTN5, in biofilm community protection from antifungal therapy and the host
Authors: Zarnowski Robert , Horton Mark V. , Johnson Chad J. , Vang Por Choua , Uram Jeremy , Fernando Liyanage Devthilini Pasasum , Vlach Jiri , Heiss Christian , Azadi Parastoo , Nett Jeniel E. , Andes David R. 
Published: February 2025

ABSTRACT

Screen of mutants from a mannosyltransferase family identified the importance of
MNT5
for
C. auris
biofilm drug resistance and neutrophil evasion. Biochemical analysis of the
mnt5∆
mutant matrix and cell wall identified alterations in the mannan structures. Resistance and matrix for
mnt5∆
were restored with delivery of wild-type matrix via extracellular vesicles. Analysis of the
mnt5
∆ cell wall revealed a reduction in mannan and compensatory increase in cell surface glucan and chitin, suggesting a role for
MNT5
in mannan masking of pathogen-associated molecular patterns.

IMPORTANCE

C. auris
recalcitrance is linked to biofilm drug resistance and immune evasion. The mannosyltransferase encoded by
MNT5
is necessary for both phenotypes and may serve as a useful therapeutic target.
A
Ralstonia solanacearum
effector regulates plant cell death by disrupting the homeostasis of the BPA1-ACD11 complex
Authors: Xue Bingbing , Zhou Yan , Xie Yongxiao , Huang Xiaocheng , Zhang Jinye , Zhang Yang , Zhong Wenyan , Zhao Jinjia , Zheng Dehong , Ruan Lifang 
Published: February 2025

ABSTRACT

Effectors secreted by phytopathogenic bacteria can suppress ETI responses induced by avirulence effectors, thereby overcoming crop resistance. However, the detailed mechanisms remain largely unknown. We report that the effector RipD from
Ralstonia solanacearum
regulates plant cell death in a protein abundance-dependent manner. RipD targets
Arabidopsis
BPA1, which directly interacts with the key cell death negative regulator ACD11. RipD competes with ACD11 for binding to BPA1, leading to the selective degradation of BPA1 via autophagy, sparing ACD11. A lower dose of RipD promotes BPA1 degradation but leads to ACD11 accumulation, thereby inhibiting RipAA-induced cell death. Conversely, higher levels of RipD degrade both BPA1 and ACD11, resulting in autophagy-dependent cell death. Visualization of RipD delivery by
R. solanacearum
indicated that it reaches levels sufficient to promote ACD11 accumulation and inhibit cell death. Our study reveals a novel mechanism by which an effector inhibits ETI and, for the first time, highlights the critical role of protein abundance in its function.

IMPORTANCE

R. solanacearum
infects major economic crops, notably tomato, potato, and tobacco, leading to substantial yield reductions and economic losses. This pathogen utilizes various type III effectors to suppress host resistance, often resulting in weakened or lost resistance. However, the underlying mechanisms remain largely unknown. Here, we reveal a novel mechanism by which RipD targets the BPA1-ACD11 complex, which is involved in host immunity and cell death. RipD regulates ACD11 protein homeostasis in a dose-dependent manner by competitively binding and activating autophagy, thereby modulating plant cell death. Importantly, visualization analysis revealed that the amount of RipD secreted by
R. solanacearum
into host cells is sufficient to inhibit Avr effector-induced cell death. Our study highlights for the first time the critical role of effector dosage, deepening the understanding of how
R. solanacearum
suppresses host ETI-related cell death and providing guidance and resources for breeding bacterial wilt resistance.
A novel plasmid-encoded transposon-derived small RNA reveals the mechanism of sRNA-regulated bacterial persistence
Authors: Lin Shu-Ling , Nie Qi-Chang , Law Carmen Oi-Kwan , Pham Hoa-Quynh , Chau Ho-Fai , Lau Terrence Chi-Kong 
Published: February 2025

ABSTRACT

Small regulatory RNAs (sRNAs) in bacteria are crucial for controlling various cellular functions and provide immediate response to the environmental stresses. Antibiotic persistence is a phenomenon that a small subpopulation of bacteria survives under the exposure of a lethal concentration of antibiotics, potentially leading to the development of drug resistance in bacteria. Here, we reported a novel transposon-derived sRNA called stnpA, which can modulate fosfomycin persistence of the bacteria. The stnpA sRNA located in the transposon with its own promoter is highly conserved among the prevalent multidrug resistance (MDR) plasmids in various pathogenic bacteria and expressed in response to the fosfomycin stress. It can directly bind to the ABC transporter, YadG, whereas this protein–RNA interaction modulated the export of fosfomycin and led to the enhancement of bacterial persistence. According to our knowledge, stnpA is the first identified transposon-derived sRNA, which controlled antibiotic persistence of bacteria, and our work demonstrated that nonresistance genes on MDR plasmids such as plasmid-encoded sRNA can provide additional survival advantages to the bacterial host against the antibiotics. In addition, the stnpA sRNA can be potentially utilized as the druggable target for the development of novel therapeutic strategies to overcome bacterial persistence.

IMPORTANCE
This study unveils a groundbreaking discovery in the realm of bacterial antibiotic persistence, highlighting the pivotal role of a newly identified small RNA (sRNA) called stnpA, which is a multidrug resistance plasmid-encoded transposon-derived sRNA that interacts directly with ABC transporter YadG to modulate the efflux of fosfomycin. Our findings elucidate a novel mechanism of small RNA-regulated fosfomycin persistence in bacteria that provides the potential pathway for the emergence of drug resistance in bacteria upon antibiotic treatment. Importantly, this study provides the first example of linking sRNA regulation to antibiotic persistence, presenting stnpA sRNA as a potential therapeutic target. This study underscores the critical role of noncoding RNAs in bacterial adaptation and offers valuable insights for developing new strategies to combat antibiotic persistence.
Nutrition-induced changes in the microbiota can cause dysbiosis and disease development
Authors: Lachnit Tim , Ulrich Laura , Willmer Fiete M. , Hasenbein Tim , Steiner Leon X. , Wolters Maria , Herbst Eva M. , Deines Peter 
Published: February 2025

ABSTRACT

Eukaryotic organisms are associated with complex microbial communities. Changes within these communities have been implicated in disease development. Nonetheless, it remains unclear whether these changes are a cause or a consequence of disease. Here, we report a causal link between environment-induced shifts in the microbiota and disease development. Using the model organism
Hydra
, we observed changes in microbial composition when transferring laboratory-grown
Hydra
to natural lake environments. These shifts were caused not only by new colonizers, through the process of community coalescence (merging of previously separate microbial communities), but also by lake water nutrients. Moreover, selective manipulation of the nutrient environment induced compound-specific shifts in the microbiota followed by disease development. Finally, L-arginine supplementation alone caused a transition in
Pseudomonas
from symbiotic to pathogenic, leading to an upregulation of immune response genes, tissue degradation, and host death. These findings challenge the notion that the host-associated microbiota is exclusively controlled by the host, highlighting the dynamic interplay between host epithelial environment, microbial colonizer pool, and nutrient conditions of the surrounding water. Furthermore, our results show that overfeeding of the microbiota allows for uncontrolled microbial growth and versatile interactions with the host. Environmental conditions may thus render symbionts a potential hazard to their hosts, blurring the divide between pathogenic and non-pathogenic microbes.

IMPORTANCE
This study highlights the critical need to understand the dynamic interplay between host-associated microbiota and environmental factors to obtain a holistic view on organismal health. Our results demonstrate that ecosystem-wide microbial trafficking (community coalescence) and environmental nutrient conditions reshape microbial communities with profound implications for host health. By exploring nutrient-driven changes in microbial composition, our research finds experimental support for the “overfeeding hypothesis,” which states that overfeeding alters the functionality of the host microbiota such that an overabundance in nutrients can facilitate disease development, transforming non-pathogenic microbes into pathogens. These findings emphasize the critical role of metabolic interactions driving microbial pathogenicity. Furthermore, our research provides empirical evidence for the “pathogenic potential” concept, challenging traditional distinctions between pathogenic and non-pathogenic microbes and supporting the idea that any microbe can become pathogenic under certain conditions.
Comparative metagenomic analysis of 16S RNA amplicon sequencing of bacterial population of an industrial site contaminated with halogenated anilines
Authors: Tobun Olukemi Ajibola , Adebusoye Sunday Adekunle , Ilori Matthew Olusoji 
Published: February 2025

ABSTRACT

Here, we use 16S rRNA gene sequencing to identify bacterial communities in three soil samples from contaminated soils with halogenated anilines and empty soil (serving as control) in Lagos state, Nigeria. BNE, BLB, and BLC had unique operational taxonomic units (OTUs) of 160, 1,797, and 4,815, respectively. Proteobacteria were the dominant phyla across all samples.
Microbiome diversity in soils of the agro-ecological zones of Bangladesh
Authors: Islam Nurul , Hoque M. Nazmul , Hossen Sabbir , Gilman Abu Ahsan , Islam Tofazzal 
Published: February 2025

ABSTRACT

Diversity and composition of soil bacteriome across various agro-ecological zones (AEZs) in Bangladesh were unveiled using 16S rRNA gene sequencing. The mapping of bacterial communities in each AEZ has laid a foundation for detailed mapping and engineering of soil microbiome in deltaic Bangladesh soils for mitigating impact of climate change and promoting sustainable agriculture.
Complete genome sequences of
Sellimonas intestinalis
JCM 30749
T
,
Sellimonas caecigallum
JCM 35759
T
, and
Sellimonas catena
JCM 35622
T
and JCM 35623
Authors: Koike Kazuyoshi , Murotomi Kazutoshi , Hamajima Mayu , Tourlousse Dieter M. , Hisatomi Atsushi , Sakamoto Mitsuo , Sekiguchi Yuji 
Published: February 2025

ABSTRACT

We obtained complete genome sequences of
Sellimonas intestinalis
JCM 30749
T
, “
Sellimonas caecigallum
” JCM 35759
T
,
Sellimonas catena
JCM 35622
T
, and
Sellimonas catena
JCM 35623. All four genomes consist of a single circular chromosome, with lengths of 2,758,996 to 3,825,976 base pairs and G + C contents of 45.12% to 45.59%.
BALF editome profiling reveals A-to-I RNA editing associated with severity and complications of
Mycoplasma pneumoniae
pneumonia in children
Authors: Jin Yun-Yun , Guo Yun , Xiong Su-Wan , Zhang Na , Chen Jian-Huan , Liu Feng 
Published: February 2025

ABSTRACT

Mycoplasma pneumoniae
is an important human respiratory pathogen that causes mild-to-moderate community-acquired
M. pneumoniae
pneumonia (MPP), particularly in children. RNA editing plays a vital role in pathogen infection and host immune response, but it remains largely unknown how it could be involved in the epigenetic regulation of host response to
M. pneumoniae
infection. In the present study, we performed an epitranscriptomic analysis of adenosine to inosine (A-to-I) editing in 39 bronchoalveolar lavage fluid (BALF) samples from the severe side (SS) and the opposite side (OS) of patients with MPP. Our editome profiling identified 87 differential RNA editing (DRE) events in 50 genes, especially missense editing events that recoded C-C motif chemokine receptor-like 2 (
CCRL2
, p.K147R) and cyclin I (
CCNI
, p.R75G). The expression of adenosine deaminase acting on RNA (
ADAR
) significantly increased on SS compared to OS and positively correlated with the average RNA editing level and individual DRE events. Meanwhile, functional enrichment analysis showed that DRE was observed in genes primarily associated with the negative regulation of innate immune response, type I interferon production, and cytokine production. Further comparison of SS between complicated MPP (CMPP) and non-complicated MPP (NCMPP) revealed RNA editing events associated with MPP complications, with a higher
ADAR
expression in CMPP than NCMPP. By identifying DRE events as biomarkers associated with MPP severity and complications, our editome profiling provides new insight into the potential role played by A-to-I RNA editing in modulating the host’s immune system during
M. pneumoniae
infection.

IMPORTANCE

Our research investigates how
Mycoplasma pneumoniae
, a common respiratory pathogen, influences how our cells modify their genetic instructions. By studying RNA editing changes in bronchoalveolar lavage fluid from patients with
M. pneumoniae
pneumonia, we aim to investigate how
M. pneumoniae
infection alters epigenetics and contributes to the disease severity and complications. Understanding such epigenetic alterations not only sheds light on the mechanisms underlying
M. pneumoniae
infection but also holds potential implications for developing better diagnostic tools and therapies. Ultimately, this work may facilitate the design of more targeted treatments to alleviate the impact of respiratory infections caused by the pathogen. Our findings may also offer broader insights into how microbial infections reshape immune processes, highlighting the importance of RNA editing in host-pathogen interactions.
Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment
Authors: Woh Pei Yee , Chen Yehao , Kumpitsch Christina , Mohammadzadeh Rokhsareh , Schmidt Laura , Moissl-Eichinger Christine 
Published: February 2025

ABSTRACT

The role of the gut archaeal microbiome (archaeome) in health and disease remains poorly understood. Methanogenic archaea have been linked to multiple sclerosis (MS), but prior studies were limited by small cohorts and inconsistent methodologies. To address this, we re-evaluated the association between methanogenic archaea and MS using metagenomic data from the International Multiple Sclerosis Microbiome Study. We analyzed gut microbiome profiles from 115 MS patients and 115 healthy household controls across Buenos Aires (27.8%), Edinburgh (33.9%), New York (10.4%), and San Francisco (27.8%). Metagenomic sequences were taxonomically classified using kraken2/bracken and a curated profiling database to detect archaea, specifically
Methanobrevibacter
species. Most MS patients were female (80/115), aged 25–72 years (median: 44.5), and 70% were undergoing treatment, including dimethyl fumarate (
n
= 21), fingolimod (
n
= 20), glatiramer acetate (
n
= 14), interferon (
n
= 18), natalizumab (
n
= 6), or ocrelizumab/rituximab (
n
= 1). We found no significant differences in overall archaeome profiles between MS patients and controls. However, treated MS patients exhibited higher abundances of
Methanobrevibacter smithii
and
M.
sp900766745 compared to untreated patients. Notably,
M.
sp900766745 abundance correlated with lower disease severity scores in treated patients. Our results suggest that gut methanogens are not directly associated with MS onset or progression but may reflect microbiome health during treatment. These findings highlight potential roles for
M. smithii
and
M.
sp900766745 in modulating treatment outcomes, warranting further investigation into their relevance to gut microbiome function and MS management.

IMPORTANCE
Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting the central nervous system, with approximately 2.8 million people diagnosed worldwide, mainly young adults aged 20–30 years. While recent studies have focused on bacterial changes in the MS microbiome, the role of gut archaea has been less explored. Previous research suggested a potential link between methanogenic archaea and MS disease status, but these findings remained inconclusive. Our study addresses this gap by investigating the gut archaeal composition in MS patients and examining how it changes in response to treatment. By focusing on methanogens, we aim to uncover novel insights into their role in MS, potentially revealing new biomarkers or therapeutic targets. This research is crucial for enhancing our understanding of the gut microbiome’s impact on MS and improving patient management.
Fur-regulated urease contributes to the environmental adaptation of
Yersinia pseudotuberculosis
Authors: Wang Junyang , Fu Peishuai , He Xinquan , Liu Yuqi , Zuo Yuxin , Wei Zhiyan , Wang Yao , Yang Yantao , Li Changfu , Shen Xihui , Zhu Lingfang 
Published: February 2025

ABSTRACT

Urease converts urea into ammonia and carbon dioxide, providing a nitrogen and carbon source for microbial growth and serving as an important mechanism for human bacterial pathogens to survive in acidic conditions, which can be regulated by many factors. As a global regulator, the ferric uptake regulator (Fur) regulates a series of genes and pathways involved in many different cellular processes and the virulence of the enteric bacterium
Yersinia pseudotuberculosis
(
Yptb
). However, whether Fur regulates the urease activity in
Yptb
was still unknown. In this study, we found that urease is positively regulated by Fur in response to manganese ions (Mn
2+
), and this regulation by Fur is mediated by specific recognition of the promoter region of urease in
Yptb
. Furthermore, urease is induced by Mn
2+
via Fur under low nutrient conditions. Moreover, we provided evidence that urease plays an important role in acid and osmotic stress resistance, biofilm formation, and virulence of
Yptb
. Our findings provide insights into understanding the regulatory mechanism and multiple functions of urease in
Yptb
.

IMPORTANCE

Urease catalyzes the breakdown of urea into ammonia and carbamate, which are widely distributed among bacterial species and play an important role as an important acid resistance system and virulence factor. In most bacterial species, urease expression is tightly regulated in response to environmental cues such as nitrogen status, pH, growth phase, substrate availability, or transcriptional regulators. In this study, we found that urease from
Yptb
is positively regulated by Fur in response to Mn
2+
under low nutrient conditions, which functions to combat acid and osmotic stress and enhance biofilm formation, and plays a crucial role in virulence. Importantly, this is the first demonstration of a direct role for Fur and Mn
2+
in regulating urease expression in
Yptb
. This study provides a comprehensive understanding of the regulatory mechanisms and functions of urease from
Yptb
.