bluuebunny/crossref_metadata_2025_split huggingface dataset:
Near-atomic structures of RHDV reveal insights into capsid assembly and different conformations between mature virion and VLP
Authors: Ruan Zhiyang , Shao Qianqian , Song Yanhua , Hu Bo , Fan Zhiyu , Wei Houjun , Liu Yunshu , Wang Fang , Fang Qianglin 
Published: October 2024

ABSTRACT

Rabbit hemorrhagic disease virus (RHDV) poses a significant threat to rabbits, causing substantial economic losses in rabbit farming. The virus also endangers wild populations of rabbit species and the predatory animals that rely on rabbits as a food source, thereby disturbing the ecological balance. However, the structural understanding of RHDV has been limited due to the lack of high-resolution structures. Here, we present the first high-resolution cryo-EM structures of the mature virion and virus-like particles (VLPs) derived from both full-length and N-terminal arm (NTA)-truncated VP60. These structures reveal intricate structural details of the icosahedral capsid and crucial NTA-mediated interactions essential for capsid assembly. In addition, dramatic conformational differences are unexpectedly observed between the mature virion and VLP. The protruding spikes of the A-B dimers adopt a “raised” state in the mature virion and a “resting” state in the VLP. These findings enhance our understanding of the structure, assembly, and conformational dynamics of the RHDV capsid, laying the essential groundwork for further virological research and therapeutic advancements.

IMPORTANCE
RHDV is a pathogen with significant economic and ecological impact. By presenting the first high-resolution cryo-EM structures of RHDV, we have uncovered detailed interactions among neighboring VP60 subunits of the icosahedral capsid. The NTA of VP60 is uniquely clustered around the threefold axis of the capsid, probably play a critical role in dragging the six VP60 dimers around the threefold axis during capsid assembly. Additionally, we observed dramatic conformational differences between the mature virion and VLPs. VLPs are commonly used for vaccine development, under the assumption that their structure closely resembles that of the mature virion. Our findings significantly advance the understanding of the RHDV capsid structure, which may be used for developing potential therapeutic strategies against RHDV.
Complete genome sequence of
Borrelia miyamotoi
strain MN18-0001, an Am-East-2 strain type isolate derived from an
Ixodes scapularis
tick (Minnesota)
Authors: Kneubehl Alexander R. , Osikowicz Lynn M. , Parise Christina M. , Van Gundy Taylor J. , Replogle Adam J. , Lopez Job E. , Eisen Rebecca J. , Hojgaard Andrias 
Published: October 2024

ABSTRACT

We report the genomic sequence of the hard tick relapsing fever spirochete
Borrelia miyamotoi
strain MN18-0001.
B. miyamotoi
causes human illness and is geographically widespread in
Ixodes
spp. (Acari: Ixodidae) ticks. This is a chromosome- and plasmid-resolved genome assembly of an Am-East-2 strain type isolate from the midwestern United States.
Metagenome-assembled genomes of
Macrocystis
-associated bacteria
Authors: Aguirre Emily G. , Schwartzman Julia A. 
Published: October 2024

ABSTRACT

Microbes are important for the development of kelp, but little is understood about the functions encoded by these microbes. Here, we assembled 1,794 metagenome-associated genomes (MAGs) from bacteria that colonize gametophytes of the giant kelp
Macrocystis pyrifera
. MAGs were grouped into 149 dereplicated strains. Functional annotation is also presented.
The draft genome sequence of a carbapenem-resistant
Klebsiella pneumoniae
strain belonging to sequence type 11 and capsular type 62
Authors: Zhang Linwan , Feng Yu , Yang Yongqiang , He Yanling , Zong Zhiyong 
Published: October 2024

ABSTRACT

Carbapenem-resistant
Klebsiella pneumoniae
(CRKP) of sequence type 11 (ST11) and capsular type KL47 or KL64 are dominant in China. We report the draft genome sequence of an ST11
bla
KPC-2
-carrying CRKP strain belonging to uncommon capsular type KL62. This strain carries virulence factors encoding multiple iron acquisition systems and mucoid regulators.
Genetic insight into the relationship between inflammatory bowel disease and
Clostridioides difficile
infection
Authors: Cushing-Damm Kelly C. , Chen Yanhua , Du Xiaomeng , Kuppa Annapurna , Raut Chinmay , Oliveri Antonino , Chen Vincent L. , Vanderwerff Brett , Zawistowski Matt , Rao Krishna , Higgins Peter , Speliotes Elizabeth K. 
Published: October 2024

ABSTRACT

Patients with inflammatory bowel disease (IBD) are at increased risk of
Clostridioides difficile
infection (CDI). Herein, we aimed to determine if genetic risk contributes to this observed association. We carried out a genome-wide association study (GWAS) analysis in the Michigan Genomics Initiative and the United Kingdom Biobank for CDI based on ICD codes and meta-analyzed these results with similar publicly accessible GWAS summary statistics from Finngen. Conditional and joint multi-SNP analyses were used to identify independent associations. Imputation of the human leukocyte antigen (HLA) region with fine mapping was used to try to identify causal HLA allele groups. Two-sample bidirectional Mendelian randomization (MR) was implemented to determine causal relationships between IBD and CDI. A total of 3,500 cases of CDI and 674,323 controls were meta-analyzed, revealing one genome-wide significant variant for CDI,
HLA-C;LINC02571
-rs3134745-C (
P
= 4.27E−08), which annotated to the major histocompatibility complex on chromosome 6. While fine mapping did not identify a statistically significant HLA allele group, there was a suggestive signal for
HLA-B
*35:01 (
P
= 4.74e−04). Using two-sample MR, genetically predicted IBD was associated with increased risk of CDI (MR Egger [odds ratio {OR} 1.16, 95% confidence interval {CI} 1.02–1.31]). Subset analysis revealed that risk was primarily driven by genetically predicted ulcerative colitis (MR Egger [OR 1.22, 95% CI 1.05–1.41]). These results highlight the importance of the host immune response in CDI pathogenesis, help explain the observed relationship between IBD and CDI, and open new avenues for targeted treatment of CDI in IBD.

IMPORTANCE
Data from this paper (i) provide reproducible evidence that susceptibility CDI is genetically mediated, (ii) highlight genetic risk as a mechanism for the increased risk of CDI in patients with inflammatory bowel disease, and (iii) point toward anti-interleukin-23 therapy as a common therapeutic strategy.
Alterations in purine and pyrimidine metabolism associated with latent tuberculosis infection: insights from gut microbiome and metabolomics analyses
Authors: Yang Boyi , Guo Xiaojing , Shi Chongyu , Liu Gang , Qin Xiaoling , Chen Shiyi , Gan Li , Liang Dongxu , Shao Kai , Xu Ruolan , Zhong Jieqing , Mo Yujie , Li Hai , Luo Dan 
Published: October 2024

ABSTRACT

Individuals with latent tuberculosis infection (LTBI) account for almost 30% of the population worldwide and have the potential to develop active tuberculosis (ATB). Despite this, the current understanding of the pathogenesis of LTBI is limited. The gut microbiome can be altered in tuberculosis patients, and an understanding of the changes associated with the progression from good health to LTBI to ATB can provide novel perspectives for understanding the pathogenesis of LTBI by identifying microbial and molecular biomarkers associated therewith. In this study, fecal samples from healthy controls (HC), individuals with LTBI and ATB patients were collected for gut microbiome and metabolomics analyses. Compared to HC and LTBI subjects, participants with ATB showed a significant decrease in gut bacterial α-diversity. Additionally, there were significant differences in gut microbial communities and metabolism among the HC, LTBI, and ATB groups. PICRUSt2 analysis revealed that microbiota metabolic pathways involving the degradation of purine and pyrimidine metabolites were upregulated in LTBI and ATB individuals relative to HCs. Metabolomic profiling similarly revealed that purine and pyrimidine metabolite levels were decreased in LTBI and ATB samples relative to those from HCs. Further correlation analyses revealed that the levels of purine and pyrimidine metabolites were negatively correlated with those of gut microbial genera represented by
Ruminococcus_gnavus_group
(
R. gnavus
), and the levels of
R. gnavus
were also positively correlated with adenosine nucleotide degradation II, which is a purine degradation pathway. Moreover, a combined signature including hypoxanthine and xanthine was found to effectively distinguish between LTBI and HC samples (area under the curve [AUC] of training set = 0.796; AUC of testing set = 0.924). Therefore, through gut microbiome and metabolomic analyses, these findings provide valuable clues regarding how alterations in gut purine and pyrimidine metabolism are linked to the pathogenesis of LTBI.

IMPORTANCE
This study provides valuable insight into alterations in the gut microbiome and metabolomic profiles in a cohort of adults with LTBI and ATB. Perturbed gut purine and pyrimidine metabolism in LTBI was associated with the compositional alterations of gut microbiota, which may be an impetus for developing novel diagnostic strategies and interventions targeting LTBI.
Histone deacetylase 2 and 3 of
Sarcoptes scabiei
: characterization of a potential drug target
Authors: He Ran , Xu Luyang , Guo Maochuan , Cheng Kai , Song Ziyi , Xie Yue , Wang Hui , Zhou Xuan , Gu Xiaobin , Xu Jing , Deng Huidan , Yang Guangyou 
Published: October 2024

ABSTRACT

Scabies is a contagious zoonotic parasitic disease that causes a substantial risk to both human and animal health and results in significant financial losses. No vaccine is available for scabies, and drug resistance to the conventional treatment for the disease has increased. Histone deacetylase (HDAC) modifies proteins by removing acetyl moieties from histones, regulates transcription, and is crucial for the immune system and apoptotic processes. This study aimed to clone, express, and determine the immunoreactivity of HDAC-2 and HDAC-3 of scabies mites to investigate their potential as scabies drug targets. The effects of inhibitors on recombinant
Sarcoptes scabiei
HDAC-2 (rSsHDAC-2) and rSsHDAC-3, as well as on the survival rate and ultrastructure of scabies mites
in vitro
, were also verified. The findings showed that the inhibitors reduced the acetylase activity of rSsHDAC-2 and rSsHDAC-3. Additionally, these inhibitors could significantly reduce the survival rate of scabies mites, making structural alterations in the mites such as mitochondrial pyknosis and cytoplasmic vacuoles and reaching a fatality rate of 76.7% after 24 h of action. In conclusion, HDAC-2 and HDAC-3 were critical to the survival of scabies mites and might be targeted by medications. Furthermore, the effect of inhibitors on the survival rate and structure of isolated scabies mites provides a new direction for developing therapeutic drugs for scabies.

IMPORTANCE
In this study, we successfully cloned and expressed recombinant SsHDAC-2 and SsHDAC-3 in a prokaryotic system and confirmed their acetylation-deacetylase activities. These results provide a solid experimental foundation for subsequent research on SsHDAC-2 and SsHDAC-3. Furthermore, we report for the first time the use of SsHDAC-2 and SsHDAC-3 as drug targets. We demonstrated that the inhibition of these HDACs by pharmacological agents can lead to structural damage in the parasite, thereby impacting the survival activity of the scabies mite. This finding opens up a novel therapeutic avenue for the treatment of scabies.
Dynamics of microbial-induced oil degradation at the microscale
Authors: Zhang Hong , Zhang Wenchao , Zong Yiwu , Kong Dongyang , Ma Luyan , Wu Xiao-Lei , Zhao Kun 
Published: October 2024

ABSTRACT

Microbial-induced oil degradation (MIOD) has a wide range of applications, such as microbial enhanced oil recovery and bioremediation of oil pollution. However, our understanding of MIOD is still far from complete. Particularly, how is the dynamics of degradation process at the microscale level with a single-cell resolution remains to be disclosed. In this work, using hexadecane droplets in water as a model system, we have studied the dynamics of hexadecane degradation by different strains, including
Pseudomonas aeruginosa
PAO1, IMP68, O-2-2, and
Dietzia
sp. DQ12-45-1b, at the microscale. Based on visualization of MIOD, the dynamics of MIOD can be characterized by a three-stage process, including adhesion, adaptation, and degradation stages. Although different strains showed similar three-stage dynamics of MIOD, the effective degradation rate varied and followed an order of PAO1 > O-2-2 > IMP68 > DQ12-45-1b under aerobic conditions. Different oxygen conditions were also tested, and the dynamics of MIOD was slowed down under anaerobic conditions in comparison to under aerobic conditions. Further investigations at the degradation stage revealed that biofilms formed at the oil-water interface enhanced oil degradation, but a prerequisite for such enhanced degradation is proper stimulation of biofilm cells in the course of biofilm formation. The findings in this work provided a detailed picture on the dynamics of MIOD at the microscale and would be beneficial for better applications of MIOD.

IMPORTANCE

Microbial-induced oil degradation is environmental friendly and economic and has become a promising technique in the fields of enhanced oil recovery and remediation of crude oil-polluted environments. For better applications of microbial-induced oil degradation, understanding the degradation dynamics particularly at the microscale is crucial. In this study, we investigated the degradation dynamics of hexadecane oil droplets incubated with different strains, including
Pseudomonas aeruginosa
PAO1, O-2-2, IMP68, and
Dietzia
sp. DQ12-45-1b at the microscale by employing microdroplet-based methods and bacterial tracking techniques. The findings in this study provided a detailed picture on the dynamics of microbial-induced oil degradation at the microscale, which will deepen our understandings on the biodegradation mechanisms of alkanes and shed insights for developing more effective biodegradation techniques.
Characteristics of methicillin-resistant
Staphylococcus aureus
isolates from bovine mastitis milk in South Korea: molecular characteristics, biofilm, virulence, and antimicrobial resistance
Authors: Kang Hye Jeong , You Ju-Yeon , Kim Seung Hoe , Moon Jin-San , Kim Ha-Young , Kim Jae-Myeong , Lee Young Ju , Kang Hyun-Mi 
Published: October 2024

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) is a drug-resistant pathogen causing subclinical and clinical bovine mastitis. This study examined the molecular properties, biofilm formation, virulence genes, and antimicrobial susceptibility of MRSA isolates from mastitis-infected dairy cow milk in South Korea. Whole-genome sequencing of an ST22-SCC
mec
IV MRSA strain positive for Panton–Valentine leukocidin (PVL) and toxic shock syndrome toxin-1 (TSST-1) was also performed. Of the 488
S
.
aureus
isolates, 30 (6.1%) were identified as MRSA, harboring the
mecA
gene. MRSA exhibited the highest resistance to kanamycin (66.7%) among non-beta-lactam antibiotics. Multidrug resistance was observed in 83.3% of MRSA isolates. All MRSA strains had the capacity to form biofilm and harbored biofilm-related genes. The primary virulence genes included
hla
,
hlb
,
lukED
,
seg
,
sei
,
sem
,
sen
, and
seo
. The ST72-t324-SCC
mec
IV genotype was the most prevalent. Of note, three ST22-SCC
mec
IV isolates were positive for PVL and TSST-1. Our findings suggest that the majority of MRSA isolates from milk obtained from dairy cows with mastitis are multidrug-resistant, capable of forming robust biofilms, and harbor multiple virulence genes. The presence of PVL- and TSST-1-positive ST22-SCC
mec
IV isolates in mastitis-infected bovine milk highlights the need for persistent monitoring to mitigate possible public health risks.

IMPORTANCE

This study reports on the presence and characteristics of methicillin-resistant
Staphylococcus aureus
strains in milk from mastitis-infected cows. To our knowledge, this is the first report of a Panton–Valentine leukocidin- and toxic shock syndrome toxin-1-positive ST22-SCC
mec
IV strain in South Korea.
The host cells suppress the proliferation of pseudorabies virus by regulating the PI3K/Akt/mTOR pathway
Authors: Xu Lei , Tao Qian , Zhang Yang , Lee Feng-qin , Xu Tong , Deng Li-shuang , Jian Zhi-jie , Zhao Jun , Lai Si-yuan , Zhou Yuan-cheng , Zhu Ling , Xu Zhi-wen 
Published: October 2024

ABSTRACT

Pseudorabies virus (PRV), a member of the alpha-herpesviruses, can infect both the nervous and reproductive systems of pigs, causing neonatal mortality and reproductive failure in sows, which incurs substantial economic losses. Neurotropism is a common characteristic of various viruses, allowing them to cross the blood-brain barrier and access the central nervous system. However, the precise mechanisms by which PRV affects the blood-brain barrier are not well understood. To investigate the mechanism of PRV’s interaction with the blood-brain barrier and its engagement with the PI3K/Akt signaling pathway during infection, an
in vitro
monolayer cell model of the blood-brain barrier was established. Our research found that PRV activates Matrix metallopeptidase 2 (MMP2), which degrades Zonula occludens-1 (ZO-1) and consequently enhances the permeability of the blood-brain barrier. PRV infection elevated the transcriptional levels of tissue inhibitor of metalloproteinases 1 (TIMP1) and inhibited its degradation through the ubiquitin-proteasome pathway, leading to higher intracellular concentrations of TIMP1 protein. TIMP1 regulates apoptosis and inhibits PRV replication in mouse brain microvascular endothelial cells through the PI3K/Akt/mTOR signaling pathway. In summary, our study delineates the mechanism through which PRV compromises the blood-brain barrier and provides insights into the host’s antiviral defense mechanisms post-infection.

IMPORTANCE
PRV, known for its neurotropic properties, is capable of inducing severe neuronal damage. Our study discovered that following PRV infection, the expression of MMP2 was upregulated, leading to the degradation of ZO-1. Furthermore, upon PRV infection in the host, the promoter of TIMP1 is significantly activated, resulting in a significant increase in TIMP1 protein levels. This upregulation of TIMP1 inhibits the proliferation of PRV through the PI3K/Akt signaling pathway. This study elucidated the mechanism through which PRV, including the PRV XJ delgE/gI/TK strains, compromises the blood-brain barrier and identifies the antiviral response characterized by the activation of the PI3K/Akt signaling pathway within infected host cells. These findings provide potential therapeutic targets for the clinical management and treatment of PRV.
Identification of receptor-binding protein and host receptor of non-lytic dsRNA phage phiNY
Authors: Ding Guoqing , Liu Hongmei , Lan Jing , Qian Tianbao , Zhou Yan , Zhu Tongyu , Zhang Tingting 
Published: October 2024

ABSTRACT

To date, complete genome sequences of 14 double-stranded RNA (dsRNA) phages are available, and studies have shown that the host range of dsRNA phages is limited. The hosts of most dsRNA phages belong to the genus
Pseudomonas
. However, the dsRNA phage phiNY, which has a non-lytic life cycle, was isolated from
Microvirgula aerodenitrificans
. Currently, the interaction between dsRNA phage phiNY and its host bacteria is unclear, which is not beneficial to a comprehensive understanding of dsRNA phage biology and the exploitation of dsRNA phage with non-lytic life cycle for biomedical applications and others. Phage adsorption is a crucial step through the interactions between receptor-binding protein (RBP) of the phage and its receptors to initiate the infection process, which dictates host range specificity. Thus, we identified the RBP and host receptor of phiNY. Through homology alignment, amino acid sequence similarity analysis, and the phylogenetic tree analysis, orf11, located in the M-segment of dsRNA phage phiNY, encodes a putative RBP. We further performed the whole-cell enzyme-linked immunosorbent assay (ELISA), western blotting assay, and indirect immunofluorescence assay and demonstrated that this orf11 is an RBP. Finally, using affinity chromatography, ELISA, and dynamic light scattering, we identified lipopolysaccharides (LPSs) on the surface of the host
M. aerodenitrificans
strain LH9 as host receptors involved in the adsorption of the dsRNA bacteriophage phiNY and observed the state of phiNY RBP after combining with LPS by atomic force microscopy. These results will guide future studies on phage-host interaction in a dsRNA phage with a non-lytic life cycle.

IMPORTANCE

The interactions between the lytic dsRNA phages and their host receptors have been clarified in previous studies. However, the interaction between the dsRNA phage phiNY (which has a non-lytic life cycle) and its host receptors during the dsRNA phage adsorption process was unknown. Here, we found that phiNY uses the orf11 protein as a receptor-binding protein (RBP). In addition, we found that this orf11 recognizes lipopolysaccharide from the host bacterium
Microvirgula aerodenitrificans
strain LH9 as a speciﬁc receptor. These results suggest that phiNY, like lytic dsRNA phages, uses an RBP to bind to a similar host receptor (i.e., lipopolysaccharide). Determining the interaction between the dsRNA phage phiNY and its host receptors will help to elucidate the mechanisms underlying the phiNY non-lytic life cycle and enhance our understanding of its infection mechanism.