bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new mechanism of respiratory syncytial virus entry inhibition by small-molecule to overcome K394R-associated resistance
Authors: Song Qiaoyun , Zhu Haoyue , Qiu Manlan , Cai Jialiao , Hu Yun , Yang Haixia , Rao Shuwen , Li Yaolan , Li Manmei , Hu Lijun , Wang Shuqin , Hong Jian , Ye Wencai , Chen Heru , Wang Ying , Tang Wei 
Published: August 2024

ABSTRACT

Infection with respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract disease in young children and older people. Despite intensive efforts over the past few decades, no direct-acting small-molecule agents against RSV are available. Most small-molecule candidates targeting the RSV fusion (F) protein pose a considerable risk of inducing drug-resistant mutations. Here, we explored the
in vitro
and
in vivo
virological properties of the K394R variant, a cross-resistant mutant capable of evading multiple RSV fusion inhibitors. Our results demonstrated that the K394R variant is highly fusogenic
in vitro
and more pathogenic than the parental strain
in vivo
. The small molecule (2
E
,2′
E
)-
N
,
N
′-((1
R
,2
S
,3
S
)−3-hydroxycyclohexane-1,2-diyl)bis(3-(2-bromo-4-fluorophenyl) acrylamide) (CL-A3-7), a structurally optimized compound derived from a natural caffeoylquinic acid derivative, substantially reduced
in vitro
and
in vivo
infections of both wild-type RSV and the K394R variant. Mechanistically, CL-A3-7 significantly inhibited virus–cell fusion during RSV entry by blocking the interaction between the viral F protein and the cellular insulin-like growth factor 1 receptor (IGF1R). Collectively, these results indicate severe disease risks caused by the K394R variant and reveal a new anti-RSV mechanism to overcome K394R-associated resistance.

IMPORTANCE

Respiratory syncytial virus (RSV) infection is a major public health concern, and many small-molecule candidates targeting the viral fusion (F) protein are associated with a considerable risk of inducing drug-resistant mutations. This study investigated virological features of the K394R variant, a mutant strain conferring resistance to multiple RSV fusion inhibitors. Our results demonstrated that the K394R variant is highly fusogenic in cell cultures and more pathogenic than the parental strain in mice. The small-molecule inhibitor CL-A3-7 substantially reduced
in vitro
and
in vivo
infections of both wild-type RSV and the K394R variant by blocking the interaction of viral F protein with its cellular receptor, showing a new mechanism of action for small-molecules to inhibit RSV infection and overcome K394R-associated resistance.
The SaeRS two-component system regulates virulence gene expression in group B
Streptococcus
during invasive infection
Authors: Coppolino Francesco , De Gaetano Giuseppe Valerio , Claverie Cosme , Sismeiro Odile , Varet Hugo , Legendre Rachel , Pellegrini Angelica , Berbiglia Alessia , Tavella Luca , Lentini Germana , Famà Agata , Barbieri Giulia , Pietrocola Giampiero , Teti Giuseppe , Firon Arnaud , Beninati Concetta 
Published: August 2024

ABSTRACT

Group B
Streptococcus
(GBS) is a pathobiont responsible for invasive infections in neonates and the elderly. The transition from a commensal to an invasive pathogen relies on the timely regulation of virulence factors. In this study, we characterized the role of the SaeRS two-component system in GBS pathogenesis. Loss-of-function mutations in the SaeR response regulator decrease virulence in mouse models of invasive infection by hindering the ability of bacteria to persist at the inoculation site and to spread to distant organs. Transcriptome and
in vivo
analysis reveal a specialized regulatory system specifically activated during infection to control the expression of only two virulence factors: the PbsP adhesin and the BvaP secreted protein. The
in vivo
surge in SaeRS-regulated genes is complemented by fine-tuning mediated by the repressor of virulence CovRS system to establish a coordinated response. Constitutive activation of the SaeRS regulatory pathway increases PbsP-dependent adhesion and invasion of epithelial and endothelial barriers, though at the cost of reduced virulence. In conclusion, SaeRS is a dynamic, highly specialized regulatory system enabling GBS to express a restricted set of virulence factors that promote invasion of host barriers and allow these bacteria to persist inside the host during lethal infection.

IMPORTANCE

Group B
Streptococcus
(or GBS) is a normal inhabitant of the human gastrointestinal and genital tracts that can also cause deadly infections in newborns and elderly people. The transition from a harmless commensal to a dangerous pathogen relies on the timely expression of bacterial molecules necessary for causing disease. In this study, we characterize the two-component system SaeRS as a key regulator of such virulence factors. Our analysis reveals a specialized regulatory system that is activated only during infection to dynamically adjust the production of two virulence factors involved in interactions with host cells. Overall, our findings highlight the critical role of SaeRS in GBS infections and suggest that targeting this system may be useful for developing new antibacterial drugs.
ASB3 expression aggravates inflammatory bowel disease by targeting TRAF6 protein stability and affecting the intestinal microbiota
Authors: Cheng Mingyang , Xu Bin , Sun Yu , Wang Junhong , Lu Yiyuan , Shi Chunwei , Pan Tianxu , Zhao Wenhui , Li Xiaoxu , Song Xiaomei , Wang Jianzhong , Wang Nan , Yang Wentao , Jiang Yanlong , Huang Haibin , Yang Guilian , Zeng Yan , Yang Dongqin , Wang Chunfeng , Cao Xin 
Published: August 2024

ABSTRACT

E3 ubiquitin ligase (E3) plays a vital role in regulating inflammatory responses by mediating ubiquitination. Previous studies have shown that ankyrin repeat and SOCS box-containing protein 3 (ASB3) is involved in immunomodulatory functions associated with cancer. However, the impact of ASB3 on the dynamic interplay of microbiota and inflammatory responses in inflammatory bowel disease (IBD) is unclear. Here, we systematically identify the E3 ligase ASB3 as a facilitative regulator in the development and progression of IBD. We observed that ASB3 exhibited significant upregulation in the lesions of patients with IBD. ASB3
−/−
mice are resistant to dextran sodium sulfate-induced colitis. IκBα phosphorylation levels and production of proinflammatory factors IL-1β, IL-6, and TNF-α were reduced in the colonic tissues of ASB3
−/−
mice compared to WT mice. This colitis-resistant phenotype was suppressed after coprophagic microbial transfer and reversed after combined antibiotics removed the gut commensal microbiome. Mechanistically, ASB3 specifically catalyzes K48-linked polyubiquitination of TRAF6 in intestinal epithelial cells. In contrast, in ASB3-deficient organoids, the integrity of the TRAF6 protein is shielded, consequently decelerating the onset of intestinal inflammation. ASB3 is associated with dysregulation of the colitis microbiota and promotes proinflammatory factors’ production by disrupting TRAF6 stability. Strategies to limit the protein level of ASB3 in intestinal epithelial cells may help in the treatment of colitis.

IMPORTANCE
Ubiquitination is a key process that controls protein stability. We determined the ubiquitination of TRAF6 by ASB3 in intestinal epithelial cells during colonic inflammation. Inflammatory bowel disease patients exhibit upregulated ASB3 expression at focal sites, supporting the involvement of degradation of TRAF6, which promotes TLR-Myd88/TRIF-independent NF-κB aberrant activation and intestinal microbiota imbalance. Sustained inflammatory signaling in intestinal epithelial cells and dysregulated protective probiotic immune responses mediated by ASB3 collectively contribute to the exacerbation of inflammatory bowel disease. These findings provide insights into the pathogenesis of inflammatory bowel disease and suggest a novel mechanism by which ASB3 increases the risk of colitis. Our results suggest that future inhibition of ASB3 in intestinal epithelial cells may be a novel clinical strategy.
Small molecule communication of
Legionella
: the ins and outs of autoinducer and nitric oxide signaling
Authors: Michaelis Sarah , Gomez-Valero Laura , Chen Tong , Schmid Camille , Buchrieser Carmen , Hilbi Hubert 
Published: August 2024

SUMMARY

Legionella pneumophila
is a Gram-negative environmental bacterium, which survives in planktonic form, colonizes biofilms, and infects protozoa. Upon inhalation of
Legionella
-contaminated aerosols, the opportunistic pathogen replicates within and destroys alveolar macrophages, thereby causing a severe pneumonia termed Legionnaires’ disease. Gram-negative bacteria employ low molecular weight organic compounds as well as the inorganic gas nitric oxide (NO) for cell-cell communication.
L. pneumophila
produces, secretes, and detects the α-hydroxyketone compound
Legionella
autoinducer-1 (LAI-1, 3-hydroxypentadecane-4-one). LAI-1 is secreted by
L. pneumophila
in outer membrane vesicles and not only promotes communication among bacteria but also triggers responses from eukaryotic cells.
L. pneumophila
detects NO through three different receptors, and signaling through the volatile molecule translates into fluctuations of the intracellular second messenger cyclic-di-guanylate monophosphate. The LAI-1 and NO signaling pathways are linked
via
the pleiotropic transcription factor LvbR. In this review, we summarize current knowledge about inter-bacterial and inter-kingdom signaling through LAI-1 and NO by
Legionella
species.
Complete genome sequences of
Escherichia coli
KA0011 clinical isolate used as a quality control strain of carbapenem susceptibility testing in Japan
Authors: Nomoto Ryohei , Nakanishi Noriko , Komatsu Shoko , Matsui Mari , Suzuki Satowa 
Published: August 2024

ABSTRACT

Escherichia coli
KA0011 had stable minimum inhibitory concentration values around the breakpoint range of meropenem and imipenem, making it suitable for use as a quality control strain for antimicrobial susceptibility testing. Here, we report the complete genomic sequence of KA0011.
Draft genomes of
Klebsiella aerogenes
,
Klebsiella huaxiensis
, and
Klebsiella michiganensis
isolates from the urinary tract
Authors: Kula Alex , Arman Muna , Appleberry Helen , Wolfe Alan J. , Putonti Catherine 
Published: August 2024

ABSTRACT

Several
Klebsiella
spp. can be the cause of urinary tract infections. Here we present the draft genome assemblies for four urinary isolates of three
Klebsiella
spp.:
Klebsiella aerogenes
UMB7541,
Klebsiella michiganensis
UMB11142 and UMB11423, and
Klebsiella huaxiensis
UMB11391 to further explore the genetic diversity of
Klebsiella
in the urinary tract.
Draft genomes of
Neisseria perflava
UMB0578,
Proteus mirabilis
UMB8339, and
Enterococcus faecalis
UMB7967 isolated from urine samples
Authors: Kula Alex , Khan Ali , Martinez Megan , Terry Jevan , Appleberry Helen , Wolfe Alan J. , Putonti Catherine 
Published: August 2024

ABSTRACT

The urinary tract of females harbors a variety of microorganisms, both for those with and without symptoms. Here, we present the draft genome sequences of three isolates from urine samples
—Neisseria perflava
UMB0578,
Proteus mirabilis
UMB8339, and
Enterococcus faecalis
UMB7967.
Genome sequence of
Lactobacillus johnsonii
XZ17, isolated from a C57BL/6J mouse lung
Authors: Ravi Keerthikka , Oh Gina J. , Moore Bethany B. , Huffnagle Gary B. , Zhou Xiaofeng 
Published: August 2024

ABSTRACT

Lactobacillus johnsonii
XZ17 was isolated from the lung homogenate of a healthy C57BL/6J mouse. XZ17 is diminished in the lungs of syngeneic bone marrow-transplanted recipient mice. Long-read sequencing of XZ17 yielded a single genome of 1,948,140 bp, with a GC content of 34.64%.
Draft genome sequences of 21
Bacillus
sp. isolates from raw bovine milk
Authors: Khullar Gauri , Cai Zhangbin , O'Brien Bridget , Suh Jinha , Ronholm Jennifer 
Published: August 2024

ABSTRACT

Members of the
Bacillus
genus are commonly used as probiotics in livestock production. We isolated several
Bacillus
strains from healthy dairy cattle. The role of these strains in mammary health is of interest. Here, we present 21 draft genome assemblies and annotations of
Bacillus
sp. isolated from fresh raw milk.
Complete genome sequences of
Geobacillus stearothermophilus
strains EF60045 and SJEF4-2 from Korean hot springs
Authors: Sung Jae-Yoon , Ganbat Dariimaa , Kim Seong Bo , Lee Sang-Jae , Lee Dong-Woo 
Published: August 2024

ABSTRACT

We report the complete genomes of
Geobacillus stearothermophilus
strains EF60045 and SJEF4-2 from Korean hot springs, with 3,769 and 3,625 thermophilic genes, respectively.
G. stearothermophilus
EF60045 shows four methylation patterns.
G. stearothermophilus
SJEF4-2 harbors three plasmids. These findings enhance understanding of
Geobacillus
strains, aiding in their development as microbial platform hosts.
Genome sequence of Xenia2 a DV cluster phage that infects
Gordonia rubripertincta
Authors: Agaiby Carol , Ahmed Maha , Argueta Aidan , Arrowood Kyle , Barrier Keelynn P. , Church Meghan W. , Connell Cheryl R. , Dao Ken D. , Dao Kathleen Huyen T. , Davenport Makenzie R. , Edmondson Megan D. , Estabrook Makenzie I. , Gondhi Santoshi , Gonzalez Patricia , Leduc Francine , Ma Trang , Mansoor Adam , Mansoor Sara , Mattley Lillian , Meyer Cyrus , Nguyen Loc , Niaz Emaan , Parker Jenna M. , Ross Delaney C. , Scott Devin M. , Semryck Brianna , Takla Kyrillos , Tiramdas Aishwarya , Upputuru Sai Kaushik , Pollenz Richard S. 
Published: August 2024

ABSTRACT

Xenia2 is a DV cluster actinobacteriophage that infects
Gordonia rubripertincta
NRRL B-16540. The genome is 68,135bp, has a GC content of 57.9% and 98 predicted protein-coding genes, 33 of which have a predicted function. Xenia2 has a lysis cassette with an endolysin (lysin A) and four different holin-like transmembrane proteins.
Genome characterization of BI2 subcluster
Streptomyces scabiei
bacteriophages GoblinVoyage and Doxi13
Authors: Jin Hanna , Chana Nihal K. , Tang Annie L. , Kaur Paramjit , Lamichhane Brishti , Leung Sze Ching , Scheiderer Diane , Sivaprakasam Vighnesh V. , Marcelino Dannah T. , Hull Gregory J. , Kamara Toma M. ,   2023 UMBC Phage Hunters,   STEM BUILD at UMBC Cohort 7, Guimaro Maria C. , Caruso Steven M. 
Published: August 2024

ABSTRACT

We present the bacteriophages GoblinVoyage and Doxi13, siphoviruses isolated on
Streptomyces scabiei
RL-34. They belong to the BI2 cluster and have genomes consisting of 60.9% GC content with identical 3’ end sticky overhangs. The genome lengths of GoblinVoyage and Doxi13 are 43,540 bp and 43,696 bp, respectively.
Genomic characterization of
Enterobacter
sp.
PGRG2
and
Achromobacter insolitus PGRG5
: bacterial strains isolated from soil present near electronics manufacture industry for heavy metal remediation
Authors: Garg Ritika , Dang Shweta , Gauba Pammi 
Published: August 2024

ABSTRACT

This article reports the whole-genome sequence of PGRG5 and the draft genome sequence of PGRG2. These strains were isolated from electronic waste contaminated soil. According to microbial identification, strain PGRG2 was identified as
Enterobacter
sp. (unclassified) with a size of ~4.4 Mbp and PGRG5 as
Achromobacter insolitus
with a size of ~6.2 Mbp.
Complete genome sequence of
Pseudomonas aeruginosa
Y010, a taro rhizosphere strain producing potent antimicrobial agents
Authors: Wen Yongqi , Cao Huiluo , Mo Zhifeng , Fang Hanshu , Xu Zeling 
Published: August 2024

ABSTRACT

Pseudomonas aeruginosa
Y010, isolated from the taro rhizosphere, exhibits great antagonistic abilities against
Dickeya
strains that cause soft-rot and blackleg diseases of plants by producing potent antimicrobial agents. The complete genome of Y010 was sequenced and annotated, which is 6,415,628 bp in length with 66.39% GC content.
Characterization and comparative genomic analysis of a marine
Bacillus
phage reveal a novel viral genus
Authors: Jin Min , Yu Meishun , Feng Xuejin , Li Yinfang , Zhang Menghui 
Published: August 2024

ABSTRACT

Bacillus pumilus
exhibits substantial economic significance, with its metabolism, adaptability, and ecological functions regulated by its bacteriophages. Here, we isolated and characterized a novel temperate phage vB_BpuM-ZY1 from
B. pumilus
derived from mangrove sediments by mitomycin C induction. Phage vB_BpuM-ZY1 is a typical myophage, which has an icosahedral head with a diameter of 43.34 ± 2.14 nm and a long contractible tail with a length of 238.58 ± 5.18 nm. Genomic analysis indicated that vB_BpuM-ZY1 encodes genes for lysogeny control, and its life cycle may be intricately regulated by multiple mechanisms. vB_BpuM-ZY1 was predicted to employ P2-like 5'-extended-cos packaging strategy. In addition, genome-wide phylogenetic tree and proteome tree analyses indicated that vB_BpuM-ZY1 belongs to the
Peduoviridae
family but forms a separate branch at a deeper taxonomic level. Particularly, the comparative genomic analysis showed that vB_BpuM-ZY1 has less than 70% intergenomic similarities with its most similar phages. Thus, we propose that vB_BpuM-ZY1 is a novel
Bacillus
phage belonging to a new genus under the
Peduoviridae
family. The protein-sharing network analysis identified 44 vB_BpuM-ZY1-related phages. Interestingly, these evolutionarily related myophages infect a broad range of hosts across different phyla, which may be explained by the high structural variations of the host recognition domain in their central spike proteins. Collectively, our study will contribute to our understanding of
Bacillus
phage diversity and
Bacillus
-phage interactions, as well as provide essential knowledge for the industrial application of
B. pumilus
.

IMPORTANCE

Although recent metagenomics research has obtained a wealth of phage genetic information, much of it is considered “dark matter” because of the lack of similarity with known sequences in the database. Therefore, the isolation and characterization of novel phages will help to interpret the vast unknown viral metagenome data and improve our understanding of phage diversity and phage-host interactions.
Bacillus pumilus
shows high economic relevance due to its wide applications in biotechnology, industry, biopharma, and environmental sectors. Since phages influence the abundance, metabolism, evolution, fitness, and ecological functions of bacteria through complex interactions, the significance of isolation and characterization of novel phages infecting
B. pumilus
is apparent. In this study, we isolated and characterized a
B. pumilus
phage belonging to a novel viral genus, which provides essential knowledge for phage biology as well as the industrial application of
B. pumilus
.
Oropharyngeal microbiome profiling and its association with age and heart failure in the elderly population from the northernmost province of China
Authors: Liu Jian , He Xiao-Yu , Yang Ke-Laier , Zhao Yue , Dai En-Yu , Chen Wen-Jia , Raj Aditya Kumar , Li Di , Zhuang Min , Yin Xin-Hua , Ling Hong 
Published: August 2024

ABSTRACT

Respiratory tract infections are the most common triggers for heart failure in elderly people. The healthy respiratory commensal microbiota can prevent invasion by infectious pathogens and decrease the risk of respiratory tract infections. However, upper respiratory tract (URT) microbiome in the elderly is not well understood. To comprehend the profiles of URT microbiota in the elderly, and the link between the microbiome and heart failure, we investigated the oropharyngeal (OP) microbiome of these populations in Heilongjiang Province, located in the North-East of China, a high-latitude and cold area with a high prevalence of respiratory tract infection and heart failure. Taxonomy-based analysis showed that six dominant phyla were represented in the OP microbial profiles. Compared with young adults, the OP in the elderly exhibited a significantly different microbial community, mainly characterized by highly prevalent
Streptococcus
,
unidentified_Saccharibacteria
,
Veillonella
,
unidentified_Pre votellaceae
, and
Neisseria
. While
unidentified_Prevotellaceae
dominated in the young OP microbiome. There was competition for niche dominance between
Streptococcus
and member of Prevotellaceae in the OP. Correlation analysis revealed that the abundance of
unidentified_Saccharibacteria
was positive, while
Streptococcus
was negatively correlated to age among healthy elderly. The bacterial structure and abundance in the elderly with heart failure were much like healthy controls. Certain changes in microbial diversity indicated the potential OP microbial disorder in heart failure patients. These results presented here identify the respiratory tract core microbiota in high latitude and cold regions, and reveal the robustness of OP microbiome in the aged, supplying the basis for microbiome-targeted interventions.

IMPORTANCE
To date, we still lack available data on the oropharyngeal (OP) microbial communities in healthy populations, especially the elderly, in high latitude and cold regions. A better understanding of the significantly changed respiratory tract microbiota in aging can provide greater insight into characteristics of longevity and age-related diseases. In addition, determining the relationship between heart failure and OP microbiome may provide novel prevention and therapeutic strategies. Here, we compared OP microbiome in different age groups and elderly people with or without heart failure in northeastern China. We found that OP microbial communities are strongly linked to healthy aging. And the disease status of heart failure was not a powerful factor affecting OP microbiome. The findings may provide basic data to reveal respiratory bacterial signatures of individuals in a cold geographic region.