bluuebunny/crossref_metadata_2025_split huggingface dataset:
The structure of lipopeptides impacts their antiviral activity and mode of action against SARS-CoV-2
in vitro
Authors: Hoste Alexis C. R. , Smeralda Willy , Cugnet Aurélien , Brostaux Yves , Deleu Magali , Garigliany Mutien , Jacques Philippe 
Published: October 2024

ABSTRACT

Microbial lipopeptides are synthesized by nonribosomal peptide synthetases and are composed of a hydrophobic fatty acid chain and a hydrophilic peptide moiety. These structurally diverse amphiphilic molecules can interact with biological membranes and possess various biological activities, including antiviral properties. This study aimed to evaluate the cytotoxicity and antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of 15 diverse lipopeptides to understand their structure-activity relationships. Non-ionic lipopeptides were generally more cytotoxic than charged ones, with cationic lipopeptides being less cytotoxic than anionic and non-ionic variants. At 100 µg/mL, six lipopeptides reduced SARS-CoV-2 RNA to undetectable levels in infected Vero E6 cells, while six others achieved a 2.5- to 4.1-log reduction, and three had no significant effect. Surfactin, white line-inducing principle (WLIP), fengycin, and caspofungin emerged as the most promising anti-SARS-CoV-2 agents. Detailed analysis revealed that these four lipopeptides affected various stages of the viral life cycle involving the viral envelope. Surfactin and WLIP significantly reduced viral RNA levels in replication assays, comparable to neutralizing serum. Surfactin uniquely inhibited viral budding, while fengycin impacted viral binding after pre-infection treatment of the cells. Caspofungin demonstrated a lower antiviral effect compared to the others. Key structural traits of lipopeptides influencing their cytotoxic and antiviral activities were identified. Lipopeptides with a high number of amino acids, especially charged (preferentially anionic) amino acids, showed potent anti-SARS-CoV-2 activity. This research paves the way for designing new lipopeptides with low cytotoxicity and high antiviral efficacy, potentially leading to effective treatments.

IMPORTANCE
This study advances our understanding of how lipopeptides, which are molecules mostly produced by bacteria, with both fat and protein components, can be used to fight viruses like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By analyzing 15 different lipopeptides, researchers identified key structural features that make some of these molecules particularly effective at reducing viral levels while being less harmful to cells. Specifically, lipopeptides with certain charged amino acids were found to have the strongest antiviral effects. This research lays the groundwork for developing new antiviral treatments that are both potent against viruses and safe for human cells, offering hope for better therapeutic options in the future.
Environment, plant genetics, and their interaction shape important aspects of sunflower rhizosphere microbial communities
Authors: Bueno de Mesquita Clifton P. , Walsh Corinne M. , Attia Ziv , Koehler Brady D. , Tarble Zachary J. , Van Tassel David L. , Kane Nolan C. , Hulke Brent S. 
Published: October 2024

ABSTRACT

Associations with soil microorganisms are crucial for plants’ overall health and functioning. While much work has been done to understand drivers of rhizosphere microbiome structure and function, the relative importance of geography, climate, soil properties, and plant genetics remains unclear, as results have been mixed and comprehensive studies across many sites and genotypes are limited. Rhizosphere microbiomes are crucial for crop resistance to pathogens, stress tolerance, nutrient availability, and ultimately yield. Here, we quantify the relative roles of plant genotype, environment, and their interaction in shaping soil rhizosphere communities, using 16S and ITS gene sequencing of rhizosphere soils from 10 genotypes of cultivated sunflower (
Helianthus annuus
) at 15 sites across the Great Plains of the United States. While site generally outweighed genotype overall in terms of effects on archaeal, bacterial, and fungal richness, community composition, and taxa relative abundances, there was also a significant interaction such that genotype exerted a significant influence on archaeal, bacterial, and fungal microbiomes in certain sites. Site effects were attributed to a combination of spatial distance and differences in climate and soil properties. Microbial taxa that were previously associated with resistance to the fungal necrotrophic pathogen
Sclerotinia
were present in most sites but differed significantly in relative abundance across sites. Our results have implications for plant breeding and agronomic microbiome manipulations for agricultural improvement across different geographic regions.

IMPORTANCE

Despite the importance of plant breeding in agriculture, we still have a limited understanding of how plant genetic variation shapes soil microbiome composition across broad geographic regions. Using 15 sites across the Great Plains of North America, we show that cultivated sunflower rhizosphere archaeal, bacterial, and fungal communities are driven primarily by site soil and climatic differences, but genotype can interact with site to influence the composition, especially in warmer and drier sites with lower overall microbial richness. We also show that all taxa that were previously found to be associated with resistance to the fungal pathogen
Sclerotinia sclerotiorum
were widespread but significantly affected by site, while a subset was also significantly affected by genotype. Our results contribute to a broader understanding of rhizosphere archaeal, bacterial, and fungal community assembly and provide foundational knowledge for plant breeding efforts and potential future microbiome manipulations in agriculture.
Environmental alkalization suppresses deployment of virulence strategies in
Pseudomonas syringae
pv.
tomato
DC3000
Authors: Yang Zichu , Wang Haibi , Keebler Robert , Lovelace Amelia , Chen Hsiao-Chun , Kvitko Brian , Swingle Bryan 
Published: October 2024

ABSTRACT

Plant pathogenic bacteria encounter a drastic increase in apoplastic pH during the early stages of plant immunity. The effects of alkalization on pathogen-host interactions have not been comprehensively characterized. Here, we used a global transcriptomic approach to assess the impact of environmental alkalization on
Pseudomonas syringae
pv.
tomato
DC3000
in vitro
. In addition to the Type 3 Secretion System, we found expression of genes encoding other virulence factors such as iron uptake and coronatine biosynthesis to be strongly affected by environmental alkalization. We also found that the activity of AlgU, an important regulator of virulence gene expression, was induced at pH 5.5 and suppressed at pH 7.8, which are pH levels that this pathogen would likely experience before and during pattern-triggered immunity, respectively. This pH-dependent control requires the presence of periplasmic proteases, AlgW and MucP, that function as part of the environmental sensing system that activates AlgU in specific conditions. This is the first example of pH-dependency of AlgU activity, suggesting a regulatory pathway model where pH affects the proteolysis-dependent activation of AlgU. These results contribute to deeper understanding of the role apoplastic pH has on host-pathogen interactions.

IMPORTANCE

Plant pathogenic bacteria, like
Pseudomonas syringae
, encounter many environmental changes including oxidative stress and alkalization during plant immunity, but the ecological effects of the individual responses are not well understood. In this study, we found that transcription of many previously characterized virulence factors in
P. syringae
pv.
tomato
DC3000 is downregulated by the level of environmental alkalization these bacteria encounter during the early stages of plant immune activation. We also report for the first time the sigma factor AlgU is post-translationally activated by low environmental pH through its natural activation pathway, which partially accounts for the expression Type 3 Secretion System virulence genes at acidic pH. The results of this study demonstrate the importance of extracellular pH on global regulation of virulence-related gene transcription in plant pathogenic bacteria.
Shedding of nontyphoidal
Salmonella
by asymptomatic convalescing children under 5 years as a risk factor for invasive disease in Mukuru informal settlement in Nairobi, Kenya
Authors: Kering Kelvin , Njaanake Kariuki , Wairimu Celestine , Mureithi Marianne , Kebenei Collins , Odityo Georgina , Mugo Michael , Kavai Susan M. , Mbae Cecilia , Weber Kristin , Pietsch Michael , Pilz Tanja , Drechsel Oliver , Thürmer Andrea , Semmler Torsten , Fuchs Stephan , Simon Sandra , Flieger Antje , Wieler Lothar H. , Kariuki Samuel 
Published: October 2024

ABSTRACT

Nontyphoidal
Salmonella
(NTS) is a predominant cause of invasive disease in sub-Saharan Africa especially among children under 5 years. Asymptomatic fecal shedding of NTS is hypothesized to contribute to the human-to-human transmission of NTS especially in low-resource settings. However, the role of pathogen shedding in invasive disease is unknown. This study aimed to investigate the prevalence and duration of fecal shedding of NTS among children under 5 years convalescing from invasive NTS disease and among healthy individuals in the community. Children presenting with fever of ≥38°C with or without diarrhea were recruited at four health facilities in Nairobi, between June 2021 and August 2023. Blood and stool samples collected were subjected to culture for the isolation of NTS (
S
. Enteritidis and
S
. Typhimurium). Children with NTS culture-positive samples (index cases) were followed up post-acute disease where household contacts and controls provided stool samples for isolation of NTS. NTS prevalence among the 3,293 individuals recruited was 1.52%. Asymptomatic shedding post-treatment was observed in almost one-third (31%) of the 42 index cases followed up. Of the 13 with intestinal shedding, 7 were shedding NTS of the same sequence type (ST) as the one recovered during acute disease. The longest duration of intestinal shedding was 3 months post-treatment. Of the 241 healthy individuals recruited, 8 had asymptomatic shedding of NTS, and 2 of these were closely related to those recovered from index cases. These findings support the hypothesis of human-to-human transmission of NTS in sub-Saharan Africa highlighting the possible benefit of vaccine introduction.

IMPORTANCE

Asymptomatic fecal shedding of nontyphoidal
Salmonella
(NTS) is hypothesized to contribute to the human-to-human transmission of NTS especially in low-resource settings which could lead to invasive disease among high-risk populations, especially children. Our findings reiterate the hypothesis that human reservoirs could be important in the transmission of nontyphoidal
Salmonella
in sub-Saharan Africa. This underscores the importance of developing infection prevention measures which could include vaccine deployment and improving water, sanitation and hygiene infrastructure.
Host blood protein biomarkers to screen for tuberculosis disease: a systematic review and meta-analysis
Authors: Gaeddert Mary , Glaser Kerstin , Chendi Bih H. , Sultanli Ayten , Koeppel Lisa , MacLean Emily L. , Broger Tobias , Denkinger Claudia M. 
Published: October 2024

ABSTRACT

Non-sputum tests are needed to improve tuberculosis (TB) diagnosis and close the diagnostic gap. The World Health Organization’s target product profile (TPP) for point-of-care (POC) screening tests requires a minimum sensitivity of 90% and a specificity of 70%. Our objective was to identify host blood protein biomarkers meeting TPP criteria. A systematic review was conducted and reported following PRISMA guidelines. Data extraction and quality assessment with Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were completed for the included studies. Heterogeneity was assessed. For biomarkers reporting sensitivity and specificity in at least four studies, a random-effects meta-analysis was performed for biomarkers with similar cut-offs. We screened 4,651 citations and included 65 studies that enrolled 16,010 participants and evaluated 156 host proteins. Most (47/65) studies enrolled adult pulmonary TB (PTB), with 15 studies in adult extra-pulmonary TB and 5 in children. Small early-stage discovery studies with case-control design were common (24/65) and had a high risk of bias. For adult PTB, CRP, IP-10, NCAM-1, and SAA met TPP criteria in high-quality studies. There was a high degree of heterogeneity in biomarker cut-offs and study design. CRP at 10 mg/L cut-off was meta-analyzed from 10 studies; pooled sensitivity 86% [95% confidence interval (CI): 80–95] and pooled specificity 67% (95% CI: 54–79). In people living with HIV (six studies), CRP pooled sensitivity was 93% (95% CI: 90–95), and pooled specificity was 59% (95% CI: 40–78). We identified promising biomarkers that performed well in high-quality studies. Data overall are limited and highly heterogenous. Further standardized validation across subgroups in prospective studies is needed before translating into POC assays.

IMPORTANCE
To our knowledge, this is the first comprehensive systematic review of host blood protein biomarkers for tuberculosis (TB), and we identified promising biomarkers for a TB screening test.
A novel machine-learning aided platform for rapid detection of urine ESBLs and carbapenemases: URECA-LAMP
Authors: Castellanos L. Ricardo , Chaffee Ryan , Kumar Hitendra , Mezgebo Biniyam Kahsay , Kassau Pawulos , Peirano Gisele , Pitout Johann D. D. , Kim Keekyoung , Pillai Dylan R. 
Published: October 2024

ABSTRACT

Pathogenic gram-negative bacteria frequently carry genes encoding extended-spectrum beta-lactamases (ESBL) and/or carbapenemases. Of great concern are carbapenem resistant
Escherichia coli
,
Klebsiella pneumoniae
,
Pseudomonas aeruginosa,
and
Acinetobacter baumannii
. Despite the need for rapid AMR diagnostics globally, current molecular detection methods often require expensive equipment and trained personnel. Here, we present a novel machine-learning-aided platform for the rapid detection of ESBLs and carbapenemases using Loop-mediated isothermal Amplification (LAMP). The platform consists of (i) an affordable device for sample lysis, LAMP amplification, and visual fluorometric detection; (ii) a LAMP screening panel to detect the most common ESBL and carbapenemase genes; and (iii) a smartphone application for automated interpretation of results. Validation studies on clinical isolates and urine samples demonstrated percent positive and negative agreements above 95% for all targets. Accuracy, precision, and recall values of the machine learning model deployed in the smartphone application were all above 92%. Providing a simplified workflow, minimal operation training, and results in less than an hour, this study demonstrated the platform’s feasibility for near-patient testing in resource-limited settings.

IMPORTANCE

Extended-spectrum beta-lactamases (ESBL) and carbapenemases confer resistance to third-generation cephalosporins and carbapenems in pathogenic Gram-negative bacteria such as
Escherichia coli
,
Klebsiella pneumoniae
,
Pseudomonas aeruginosa,
and
Acinetobacter baumannii
. Conventional antimicrobial susceptibility testing is based on phenotypic methods, and results can take several days to be obtained. Current genotypic detection methods can be rapid but require expensive equipment and trained personnel. In this study, we present a novel machine learning-aided platform for the rapid detection of ESBLs and carbapenemases using Loop-mediated isothermal Amplification (LAMP). The validation of the platform demonstrated percent positive and negative agreements above 95% for all targets. The newly developed platform provided a simplified workflow, minimal technical training, and results in less than an hour. This study demonstrated the platform’s feasibility for rapid testing of ESBL and carbapenemases in bacteria and urine specimens.
DCLK1 mediated cooperative acceleration of EMT by avian leukosis virus subgroup J and Marek’s disease virus via the Wnt/β-catenin pathway promotes tumor metastasis
Authors: Zhou Jing , Zhou Defang , Zhang Qian , Zhang Xinyue , Liu Xiaoyang , Ding Longying , Wen Jing , Xu Xiaoyu , Cheng Ziqiang 
Published: October 2024

ABSTRACT

Co-infection with oncogenic retrovirus and herpesvirus significantly facilitates tumor metastasis in human and animals. Co-infection with avian leukosis virus subgroup J (ALV-J) and Marek’s disease virus (MDV), which are typical oncogenic retrovirus and herpesvirus, respectively, leads to enhanced oncogenicity and accelerated tumor formation, resulting in increased mortality of affected chickens. Previously, we found that ALV-J and MDV cooperatively promoted tumor metastasis. However, the molecular mechanism remains elusive. Here, we found that doublecortin-like kinase 1 (DCLK1) mediated cooperative acceleration of epithelial–mesenchymal transition (EMT) by ALV-J and MDV promoted tumor metastasis. Mechanistically, DCLK1 induced EMT via activating Wnt/β-catenin pathway by interacting with β-catenin, thereby cooperatively promoting tumor metastasis. Initially, we screened and found that DCLK1 was a potential mediator for the cooperative activation of EMT by ALV-J and MDV, and enhanced cell proliferation, migration, and invasion. Subsequently, we revealed that DCLK1 physically interacted with β-catenin to promote the formation of the β-catenin–TCF4 complex, inducing transcription of the Wnt target gene, c-Myc, promoting EMT by increasing the expression of N-cadherin, Vimentin, and Snail, and decreasing the expression of E-cadherin. Taken together, we discovered that jointly activated DCLK1 by ALV-J and MDV accelerated cell proliferation, migration and invasion, and ultimately activated EMT, paving the way for tumor metastasis. This study elucidated the molecular mechanism underlying cooperative metastasis induced by co-infection with retrovirus and herpesvirus.

IMPORTANCE
Tumor metastasis, a complex phenomenon in which tumor cells spread to new organs, is one of the greatest challenges in cancer research and is the leading cause of cancer-induced death. Numerous studies have shown that oncoviruses and their encoded proteins significantly affect metastasis, especially the EMT process. ALV-J and MDV are classic tumorigenic retrovirus and herpesvirus, respectively. We found that ALV-J and MDV synergistically promoted EMT. Further, we identified the tumor stem cell marker DCLK1 in ALV-J and MDV co-infected cells. DCLK1 directly interacted with β-catenin, promoting the formation of the β-catenin–TCF4 complex. This interaction activated the Wnt/β-catenin pathway, thereby inducing EMT and paving the way for synergistic tumor metastasis. Exploring the molecular mechanisms by which ALV-J and MDV cooperate during EMT will contribute to our understanding of tumor progression and metastasis. This study provides new insights into the cooperative induced tumor metastasis by retroviruses and herpesviruses.
Genome sequence of the marine alphaproteobacterium
Lentilitoribacter
sp. EG35 isolated from the temperate octocoral
Eunicella gazella
Authors: Keller-Costa Tina , Madureira Selene , Fernandes Ana S. , Kozma Lydia , Gonçalves Jorge M.S. , Barroso Cristina , Egas Conceição , Costa Rodrigo 
Published: October 2024

ABSTRACT

We report the genome sequence of
Lentilitoribacter
sp. strain EG35 isolated from the octocoral
Eunicella gazella
sampled off the coast of Portugal. We reveal the coding potential for the biosynthesis of polyhydroxyalkanoates — biodegradable polyesters that may serve bioplastics production, diverse homoserine lactone-like communication signals, and four putatively novel natural products.
Whole-genome sequence of
Bacillus paralicheniformis
strain R243 isolated from rice (
Oryza sativa
L.) roots
Authors: Chebotar Vladimir K. , Gancheva Maria S. , Keleinikova Oksana V. , Baganova Maria E. , Zaplatkin Alexander N. , Pishchik Veronika N. , Chizhevskaya Elena P. 
Published: October 2024

ABSTRACT

We isolated an endophytic strain R243 and sequenced its genome using the NextSeq 1000 (Illumina) sequencing platform. The sequenced genome contains 4,478 protein-coding genes with a mean GC content of 45.56%. The strain R243 was identified as
Bacillus paralicheniformis
. Gene clusters involved in the synthesis of biocontrol substances were identified.
The
Plasmodium falciparum
histone methyltransferase SET10 participates in a chromatin modulation network crucial for intraerythrocytic development
Authors: Musabyimana Jean-Pierre , Musa Sherihan , Manti Janice , Distler Ute , Tenzer Stefan , Ngwa Che Julius , Pradel Gabriele 
Published: October 2024

ABSTRACT

The lifecycle progression of the malaria parasite
Plasmodium falciparum
requires precise tuning of gene expression including histone methylation. The histone methyltransferase
Pf
SET10 was previously described as an H3K4 methyltransferase involved in
var
gene regulation, making it a prominent antimalarial target. In this study, we investigated the role of
Pf
SET10 in the blood stages of
P. falciparum
in more detail, using tagged
Pf
SET10-knockout (KO) and -knockdown (KD) lines. We demonstrate a nuclear localization of
Pf
SET10 with peak protein levels in schizonts.
Pf
SET10 deficiency reduces intraerythrocytic growth but has no effect on gametocyte commitment and maturation. Screening of the
Pf
SET10-KO line for histone methylation variations reveals that lack of
Pf
SET10 renders the parasites unable to mark H3K18me1, while no reduction in the H3K4 methylation status could be observed. Comparative transcriptomic profiling of
Pf
SET10-KO schizonts shows an upregulation of transcripts particularly encoding proteins linked to red blood cell remodeling and antigenic variation, suggesting a repressive function of the histone methylation mark. TurboID coupled with mass spectrometry further highlights an extensive nuclear
Pf
SET10 interaction network with roles in transcriptional regulation and mRNA processing, DNA replication and repair, and chromatin remodeling. The main interactors of
Pf
SET10 include ApiAP2 transcription factors, epigenetic regulators like
Pf
HDAC1, chromatin modulators like
Pf
MORC and
Pf
ISWI, mediators of RNA polymerase II, and DNA replication licensing factors. The combined data pinpoint
Pf
SET10 as a histone methyltransferase essential for H3K18 methylation that regulates nucleic acid metabolic processes in the
P. falciparum
blood stages as part of a comprehensive chromatin modulation network.

IMPORTANCE

The fine-tuned regulation of DNA replication and transcription is particularly crucial for the rapidly multiplying blood stages of malaria parasites and proteins involved in these processes represent important drug targets. This study demonstrates that contrary to previous reports the histone methyltransferase
Pf
SET10 of the malaria parasite
Plasmodium falciparum
promotes the methylation of histone 3 at lysine K18, a histone mark to date not well understood. Deficiency of
Pf
SET10 due to genetic knockout affects genes involved in intraerythrocytic development. Furthermore, in the nuclei of blood-stage parasites,
Pf
SET10 interacts with various protein complexes crucial for DNA replication, remodeling, and repair, as well as for transcriptional regulation and mRNA processing. In summary, this study highlights
Pf
SET10 as a methyltransferase affecting H3K18 methylation with critical functions in chromatin maintenance during the development of
P. falciparum
in red blood cells.