bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case for implementing an HSV1/2, VZV, and syphilis lesion panel in Manitoba, Canada
Authors: Hedley Adam , Bullard Jared , Van Caeseele Paul , Shaw Souradet , Tsang Raymond , Alexander David C. , Dust Kerry , Stein Derek R. 
Published: June 2024

ABSTRACT

Syphilis, caused by
Treponema pallidum
subsp.
pallidum
(TPA), is becoming a significant public health concern, with rising incidence in Manitoba exceeding the national average. The province has also seen a demographic shift leading to women representing 51.9% of cases in 2021, leading to the re-emergence of congenital syphilis. Given the similarities in lesion appearance between TPA and other pathogens such as herpesviruses, accurate diagnosis is crucial for effective management and prevention. In order to address the potential for missed TPA cases, we conducted a quality assurance study from June 2021 to March 2023, screening over 5,000 mucocutaneous lesion swabs for TPA, initially submitted for herpes simplex virus (HSV) and varicella zoster virus (VZV) testing. Positivity rates were 13% for HSV1, 13% for HSV2, 6.7% for VZV, and 6.6% for TPA. Turnaround times (TAT) for TPA testing, as a send-out to the reference laboratory, averaged 17.8 days. Of the TPA-positive specimens, 36% did not have a corresponding TPA PCR test ordered, and 19% did not have accompanying syphilis serology within 30 days of collection. Creation of a multiplex lesion panel identified high sensitivity and specificity for HSV1, HSV2, VZV, and TPA, with robust reproducibility across multiple runs. Incorporation of TPA into a lesion panel improved the TAT to 4 days. Our findings emphasize the need for improved testing strategies to combat the syphilis epidemic and enhance public health outcomes.

IMPORTANCE
Syphilis resurgence has become a significant global public health concern. In particular, the Canadian Prairies have been struggling with high incidence since 2016, exceeding the national Canadian average. We undertook a quality assurance study that highlighted significant gaps in diagnosis of acute syphilis, which led to the development of a highly sensitive and specific multiplex lesion assay for the dual detection of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella zoster virus (VZV), and syphilis.
Quantitative analysis of the lysine acetylome reveals the role of SIRT3-mediated HSP60 deacetylation in suppressing intracellular
Mycobacterium tuberculosis
survival
Authors: Zhu Chuanzhi , Duan Yuheng , Dong Jing , Jia Hongyan , Zhang Lanyue , Xing Aiying , Li Zihui , Du Boping , Sun Qi , Huang Yinxia , Zhang Zongde , Pan Liping 
Published: June 2024

ABSTRACT

Protein acetylation and deacetylation are key epigenetic modifications that regulate the initiation and development of several diseases. In the context of infection with
Mycobacterium tuberculosis
(
M. tb
), these processes are essential for host–pathogen interactions and immune responses. However, the specific effects of acetylation and deacetylation on cellular functions during
M. tb
infection are not fully understood. This study employed Tandem Mass Tag (TMT) labeling for quantitative proteomic profiling to examine the acetylproteome (acetylome) profiles of noninfected and
M. tb
-infected macrophages. We identified 715 acetylated peptides from 1,072 proteins and quantified 544 lysine acetylation sites (Kac) in 402 proteins in noninfected and
M. tb
-infected macrophages. Our research revealed a link between acetylation events and metabolic changes during
M. tb
infection. Notably, the deacetylation of heat shock protein 60 (HSP60), a key chaperone protein, was significantly associated with this process. Specifically, the deacetylation of HSP60 at K96 by sirtuin3 (SIRT3) enhances macrophage apoptosis, leading to the elimination of intracellular
M. tb
. These findings underscore the pivotal role of the SIRT3–HSP60 axis in the host immune response to
M. tb
. This study offers a new perspective on host protein acetylation and suggests that targeting host-directed therapies could be a promising approach for tuberculosis immunotherapy.

IMPORTANCE

Protein acetylation is crucial for the onset, development, and outcome of tuberculosis (TB). Our study comprehensively investigated the dynamics of lysine acetylation during
M. tb
infection, shedding light on the intricate host–pathogen interactions that underlie the pathogenesis of tuberculosis. Using an advanced quantitative lysine proteomics approach, different profiles of acetylation sites and proteins in macrophages infected with
M. tb
were identified. Functional enrichment and protein–protein network analyses revealed significant associations between acetylated proteins and key cellular pathways, highlighting their critical role in the host response to
M. tb
infection. Furthermore, the deacetylation of HSP60 and its influence on macrophage-mediated clearance of
M. tb
underscore the functional significance of acetylation in tuberculosis pathogenesis. In conclusion, this study provides valuable insights into the regulatory mechanisms governing host immune responses to
M. tb
infection and offers promising avenues for developing novel therapeutic interventions against TB.
Construction and immunogenicity of SARS-CoV-2 virus-like particle expressed by recombinant baculovirus BacMam
Authors: Nguyen Hai Trong , Falzarano Darryl , Gerdts Volker , Liu Qiang 
Published: June 2024

ABSTRACT

The pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve to give rise to variants of concern that can escape vaccine-induced immunity. As such, more effective vaccines are urgently needed. In this study, we evaluated virus-like particle (VLP) as a vaccine platform for SARS-CoV-2. The spike, envelope, and membrane proteins of the SARS-CoV-2 Wuhan strain were expressed by a single recombinant baculovirus BacMam and assembled into VLPs in cell culture. The morphology and size of the SARS-CoV-2 VLP as shown by transmission electron microscopy were similar to the authentic SARS-CoV-2 virus particle. In a mouse trial, two intramuscular immunizations of the VLP BacMam with no adjuvant elicited spike-specific binding antibodies in both sera and bronchoalveolar lavage fluids. Importantly, BacMam VLP-vaccinated mouse sera showed neutralization activity against SARS-CoV-2 spike pseudotyped lentivirus. Our results indicated that the SARS-CoV-2 VLP BacMam stimulated spike-specific immune responses with neutralization activity.

IMPORTANCE
Although existing vaccines have significantly mitigated the impact of the COVID-19 pandemic, none of the vaccines can induce sterilizing immunity. The spike protein is the main component of all approved vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due primarily to its ability to induce neutralizing antibodies. The conformation of the spike protein in the vaccine formulation should be critical for the efficacy of a vaccine. By way of closely resembling the authentic virions, virus-like particles (VLPs) should render the spike protein in its natural conformation. To this end, we utilized the baculovirus vector, BacMam, to express virus-like particles consisting of the spike, membrane, and envelope proteins of SARS-CoV-2. We demonstrated the immunogenicity of our VLP vaccine with neutralizing activity. Our data warrant further evaluation of the virus-like particles as a vaccine candidate in protecting against virus challenges.
Determining the functional role of the
Gluconobacter oxydans
GOX1969 protein as a BamB homolog
Authors: Ariano Ky , Schweiger Paul 
Published: June 2024

ABSTRACT

Acetic acid bacteria are used in many industrial processes such as the production of vinegar, vitamin C, the antidiabetic drug miglitol, and various artificial flavorings. These industrially important reactions are primarily carried out by an arsenal of periplasmic-facing membrane-bound dehydrogenases that incompletely oxidize their substrates and shuttle electrons directly into the respiratory chain. Among these dehydrogenases, GOX
1969
in
Gluconobacter oxydans
was predicted to be a pyrroloquinoline quinone-dependent dehydrogenase of unknown function. However, after multiple analysis by a number of labs, no dehydrogenase activity has been detected. Reanalysis of GOX1969 sequence and structure reveals similarities to
Escherichia coli
BamB, which functions as a subunit of the β-barrel assembly machinery complex that is responsible for the assembly of β-barrel outer membrane proteins in Gram-negative bacteria. To test if the physiological function of GOX1969 is similar to BamB in
E. coli
, we introduced the
gox1969
gene into an
E. coli
∆
bamB
mutant. Growth deficiencies in the ∆
bamB
mutant were restored when
gox1969
was expressed on the plasmid pGox1969. Furthermore, increased membrane permeability conferred by
bamB
deletion was restored upon
gox1969
expression, which suggests a direct link between GOX1969 and a role in maintaining outer membrane stability. Together, this evidence strongly suggests that GOX1969 is functionally acting as a BamB in
G. oxydans
. As such, functional information on uncharacterized genes will provide new insights that will allow for more accurate modeling of acetic acid bacterial metabolism and further efforts to design rational strains for industrial use.

IMPORTANCE

Gluconobacter oxydans
is an industrially important member of the acetic acid bacteria. Experimental characterization of putative genes is necessary to identify targets for further engineering of rational acetic acid bacteria strains that can be used in the production of vitamin C, antidiabetic compounds, artificial flavorings, or novel compounds. In this study, we have identified an undefined dehydrogenase GOX1969 with no known substrate and defined structural similarities to outer membrane biogenesis protein BamB in
E. coli
K12. Furthermore, we demonstrate that GOX1969 is capable of complementing
bamB
knockout phenotypes in
E. coli
K12. Taken together, these findings enhance our understanding of
G. oxydans
physiology and expand the list of potential targets for future industrial strain design.
Exploring antimicrobial resistance determinants in the Neanderthal microbiome
Authors: Sankaranarayanan Gomathinayagam , Kodiveri Muthukaliannan Gothandam 
Published: June 2024

ABSTRACT

This study aimed to investigate the presence of antimicrobial resistance determinants (ARDs) in the Neanderthal microbiome through meticulous analysis of metagenomic data derived directly from dental calculus and fecal sediments across diverse Neanderthal sites in Europe. Employing a targeted locus mapping approach followed by a consensus strategy instead of an assembly-first approach, we aimed to identify and characterize ARDs within these ancient microbial communities. A comprehensive and redundant ARD database was constructed by amalgamating data from various antibiotic resistance gene repositories. Our results highlighted the efficacy of the KMA tool in providing a robust alignment of ancient metagenomic reads to the antibiotic resistance gene database. Notably, the KMA tool identified a limited number of ARDs, with only the 23S ribosomal gene from the dental calculus sample of Neanderthal remains at Goyet Troisieme Caverne exhibiting ancient DNA (aDNA) characteristics. Despite not identifying ARDs with typical ancient DNA damage patterns or negative distance proportions, our findings suggest a nuanced identification of putative antimicrobial resistance determinants in the Neanderthal microbiome’s genetic repertoire based on the taxonomy–habitat correlation. Nevertheless, our findings are limited by factors such as environmental DNA contamination, DNA fragmentation, and cytosine deamination of aDNA. The study underscores the necessity for refined methodologies to unlock the genomic assets of prehistoric populations, fostering a comprehensive understanding of the intricate dynamics shaping the microbial landscape across history.

IMPORTANCE
The results of our analysis demonstrate the challenges in identifying determinants of antibiotic resistance within the endogenous microbiome of Neanderthals. Despite the comprehensive investigation of multiple studies and the utilization of advanced analytical techniques, the detection of antibiotic resistance determinants in the ancient microbial communities proved to be particularly difficult. However, our analysis did reveal the presence of some authentic ancient conservative genes, indicating the preservation of certain genetic elements over time. These findings raise intriguing questions about the factors influencing the presence or absence of antibiotic resistance in ancient microbial communities. It could be speculated that the spread of current antibiotic resistance, which has reached alarming levels in modern times, is primarily driven by anthropogenic factors such as the widespread use and misuse of antibiotics in medical and agricultural practices.
A comparative cell wall analysis of
Trichoderma
spp. confirms a conserved polysaccharide scaffold and suggests an important role for chitosan in mycoparasitism
Authors: Kappel Lisa , Yu Long , Escobar Carolina , Marcianò Demetrio , Srivastava Vaibhav , Bulone Vincent , Gruber Sabine 
Published: June 2024

ABSTRACT

Fungal cell walls are dynamic extracellular matrices that enable efficient adaptation to changing environments. While the cell wall compositions of yeasts, human, and plant pathogenic fungi have been studied to some extent, the cell walls of mycoparasites remain poorly characterized.
Trichoderma
species comprise a diverse group of soil fungi with different survival strategies and lifestyles. The comparative study of cell wall carbohydrate-active enzymes in 13
Trichoderma
spp. revealed that the types of enzymes involved in chitin and chitosan metabolism are phylogenetically distant between mycoparasitic and saprotrophic species. Here, we compare the carbohydrate composition and function of the cell wall of a saprotrophic strain
Trichoderma reesei
with that of the mycoparasitic, biological control agent
Trichoderma atroviride
. Monosaccharide and glycosidic linkage analyses as well as dual
in situ
interaction assays showed that the cell wall polysaccharide composition is conserved between both species, except for the amounts of chitin detected. The results suggest that the observed accumulation of chitosan during mycoparasitism may prevent host recognition. Remarkably,
Trichoderma atroviride
undergoes dynamic cell wall adaptations during both vegetative development and mycoparasitism, which appears to be confirmed by an evolutionarily expanded group of specialized enzymes. Overall, our analyses support the notion that habitat specialization is reflected in cell wall architecture and that plastic chitin remodeling may confer an advantage to mycoparasites, ultimately enabling the successful invasion and parasitism of plant pathogens. This information may potentially be exploited for the control of crop diseases using biological agents.

IMPORTANCE

Trichoderma
species are emerging model fungi for the development of biocontrol agents and are used in industrial biotechnology as efficient enzyme producers. Fungal cell walls are complex structures that differ in carbohydrate, protein, and enzyme composition across taxa. Here, we present a chemical characterization of the cell walls of two
Trichoderma
spp., namely the predominantly saprotrophic
Trichoderma reesei
and the mycoparasite
Trichoderma atroviride
. Chemical profiling revealed that
Trichoderma
spp. remodel their cell wall to adapt to particular lifestyles, with dynamic changes during vegetative development. Importantly, we found that chitosan accumulation during mycoparasitism of a fungal host emerged as a sophisticated strategy underpinning an effective attack. These insights shed light on the molecular mechanisms that allow mycoparasites to overcome host defenses and can be exploited to improve the application of
T. atroviride
in biological pest control. Moreover, our results provide valuable information for targeting the fungal cell wall for therapeutic purposes.
The microbiome compositional and functional differences between rectal mucosa and feces
Authors: Yin Xiao-Fei , Ye Taoyu , Chen Han-Lin , Liu Junyan , Mu Xue-Feng , Li Hao , Wang Jun , Hu Yuan-Jia , Cao Hongzhi , Kang Wen-Quan 
Published: June 2024

ABSTRACT

In recent years, most studies on the gut microbiome have primarily focused on feces samples, leaving the microbial communities in the intestinal mucosa relatively unexplored. To address this gap, our study employed shotgun metagenomics to analyze the microbial compositions in normal rectal mucosa and matched feces from 20 patients with colonic polyps. Our findings revealed a pronounced distinction of the microbial communities between these two sample sets. Compared with feces, the mucosal microbiome contains fewer genera, with Burkholderia being the most discriminating genus between feces and mucosa, highlighting its significant influence on the mucosa. Furthermore, based on the microbial classification and KEGG Orthology (KO) annotation results, we explored the association between rectal mucosal microbiota and factors such as age, gender, BMI, and polyp risk level. Notably, we identified novel biomarkers for these phenotypes, such as
Clostridium ramosum
and
Enterobacter cloacae
in age. The mucosal microbiota showed an enrichment of KO pathways related to sugar transport and short chain fatty acid metabolism. Our comprehensive approach not only bridges the knowledge gap regarding the microbial community in the rectal mucosa but also underscores the complexity and specificity of microbial interactions within the human gut, particularly in the Chinese population.

IMPORTANCE
This study presents a system-level map of the differences between feces and rectal mucosal microbial communities in samples with colorectal cancer risk. It reveals the unique microecological characteristics of rectal mucosa and its potential influence on health. Additionally, it provides novel insights into the role of the gut microbiome in the pathogenesis of colorectal cancer and paves the way for the development of new prevention and treatment strategies.
Comparative transcriptomic insights into molecular mechanisms of the susceptibility wheat variety MX169 response to
Puccinia striiformis
f. sp.
tritici
(
Pst
) infection
Authors: Lv Xuan , Deng Jie , Zhou Congying , Abdullah Ahsan , Yang Ziqian , Wang Zhifang , Yang Lujia , Zhao Baoqiang , Li Yuchen , Ma Zhanhong 
Published: June 2024

ABSTRACT

Stripe rust of wheat is caused by the fungal pathogen
Puccinia striiformis
f. sp.
tritici
(
Pst
). Breeding durably resistant wheat varieties by disrupting the susceptibility (
S
) gene has an important impact on the control of wheat stripe rust. Mingxian169 (MX169) showed strong stripe rust susceptibility to all the races of
Pst
. However, molecular mechanisms and responsive genes underlying susceptibility of the wheat variety MX169 to
Pst
have not been elucidated. Here, we utilized next-generation sequencing technology to analyze transcriptomics data of “MX169” and high-resistance wheat “Zhong4” at 24, 48, and 120 h post-inoculation (hpi) with
Pst
. Comparative transcriptome analysis revealed 3,494, 2,831, and 2,700 differentially expressed genes (DEGs) at different time points. We observed an upregulation of DEGs involved in photosynthesis, flavonoid biosynthesis, pyruvate metabolism, thiamine metabolism, and other biological processes, suggesting their involvement in MX169’s response to
Pst
. DEGs encoding transcription factors were also identified. Our study suggested the potential susceptibility gene resources in MX169 related to stripe rust response could be valuable for understanding the mechanisms involved in stripe rust susceptibility and for improving wheat resistance to
Pst
.

IMPORTANCE

Our study suggests the potential susceptibility gene resources in MX169 related to stripe rust response could be valuable for understanding the mechanisms involved in stripe rust susceptibility and for improving wheat resistance to
Pst
.
Longitudinal alterations in the urinary virome of kidney transplant recipients are influenced by BK viremia and patient sex
Authors: Maqsood Rabia , Wu Lily I. , Brennan Daniel C. , Lim Efrem S. 
Published: June 2024

ABSTRACT

Little is known about the urinary virome and how it interacts with the host, particularly in renal transplant diseases. Using metagenomic sequencing, we characterized the urinary virome of 23 kidney transplant recipients longitudinally (11 BKV+ patients and 12 BKV− patients). We applied linear mixed effects models, PERMANOVA, k-means clustering, and MaAsLin2 algorithms to determine virome signatures associated with post-transplant time, BK viremia status, and patient sex. We found that the richness and alpha diversity of urinary virome were significantly different in renal transplant recipients with BKV+ over time in comparison to BKV− (richness
P
= 0.012, alpha
P
< 0.0001). Female BKV− patients had significantly higher virome richness than males (
P
= 0.0063). Virome beta diversity was significantly different between patients by BKV status (
P
< 0.001). Additionally, we identified underlying interactions between patient sex and BKV status, in terms of virome beta diversity (
P
= 0.008). BK polyomavirus infections were primarily of subtypes IA, IB1, and IB2. The non-BK dominant samples clustered into six urinary virome community states. BKV− samples had more anelloviruses than BKV+ samples though this difference was not statistically significant. Lastly, we identified specific viruses, associated with BKV+ and time in our samples. Our results indicate that dynamic alterations in the urinary virome over the post-transplant period in kidney transplant recipients can be shaped by BK viremia and patient sex. These findings advance our fundamental understanding of the urinary virome and support a new line of investigation in renal disease and transplantation.

IMPORTANCE
The urinary microbiome is increasingly implicated in renal health and disease. While most research focuses on bacteria communities of the microbiome, factors that influence the urinary virome are not understood. Here, we investigated the urinary virome of 23 adult kidney transplant recipients longitudinally over 14 weeks post-transplant. We show that alterations in the urinary virome are associated with kidney transplant recipients with BK polyomavirus viremia that can lead to BK nephropathy and allograft rejection. By modeling the temporal dynamics post-transplant, we delineated specific profiles of the urinary virome associated with patient sex and urinary community states. These findings reveal fundamental aspects of the urinary virome that can be leveraged to better manage kidney diseases.