bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenine nucleotide translocator and ATP synthase cooperate in mediating the mitochondrial permeability transition
Authors: Tommasin Ludovica , Carrer Andrea , Nata Federica Boscolo , Frigo Elena , Fogolari Federico , Lippe Giovanna , Carraro Michela , Bernardi Paolo 
Published: January 2025

AbstractThe permeability transition (PT) is a permeability increase of the mitochondrial inner membrane causing mitochondrial swelling in response to matrix Ca2+. The PT is mediated by regulated channel(s), the PT pore(s) (PTP), which can be generated by at least two components, adenine nucleotide translocator (ANT) and ATP synthase. Whether these provide independent permeation pathways remains to be established. Here, we assessed the contribution of ANT to the PT based on the effects of the selective ANT inhibitors atractylate (ATR) and bongkrekate (BKA), which trigger and inhibit channel formation by ANT, respectively. BKA partially inhibited Ca2+‐dependent PT and did not prevent the inducing effect of phenylarsine oxide, which was still present in mouse embryonic fibroblasts deleted for all ANT isoforms. The contribution of ANT to the PT emerged at pH 6.5 (a condition that inhibits ATP synthase channel opening) in the presence of ATR, which triggered mitochondrial swelling and elicited currents in patch‐clamped mitoplasts. Unexpectedly, ANT‐dependent PT at pH 6.5 could also be stimulated by benzodiazepine‐423 [a selective ligand of the oligomycin sensitivity conferral protein (OSCP) subunit of ATP synthase], suggesting that the ANT channel is regulated by the peripheral stalk of ATP synthase. In keeping with docking simulations, ANT could be co‐immunoprecipitated with ATP synthase subunits c and g, and oligomycin (which binds adjacent c subunits) decreased the association of ANT with subunit c. These results reveal a close cooperation between ANT and ATP synthase in the PT and open new perspectives in the study of this process.
imageKey points
We have assessed the relative role of adenine nucleotide translocator (ANT) and ATP synthase in generating the mitochondrial permeability transition (PT).
At pH 7.4, bongkrekate had little effect on Ca2+‐dependent PT, and did not prevent the inducing effect of phenylarsine oxide, which was still present in mouse embryonic fibroblasts deleted for all ANT isoforms.
The contribution of ANT emerged at pH 6.5 (which inhibits ATP synthase channel opening) in the presence of atractylate, which triggered mitochondrial swelling and elicited currents in patch‐clamped mitoplasts.
Benzodiazepine‐423, a selective ligand of the oligomycin sensitivity conferral protein subunit of ATP synthase, stimulated ANT‐dependent PT at pH 6.5, suggesting that the ANT channel is regulated by the peripheral stalk of ATP synthase.
ANT could be co‐immunoprecipitated with ATP synthase subunits c and g; oligomycin, which binds adjacent c subunits, decreased the association with subunit c, in keeping with docking simulations.
Single-cell phenotyping of extracellular electron transfer via microdroplet encapsulation
Authors: Partipilo Gina , Bowman Emily K. , Palmer Emma J. , Gao Yang , Ridley Rodney S. , Alper Hal S. , Keitz Benjamin K. 
Published: January 2025

ABSTRACT

Electroactive organisms contribute to metal cycling, pollutant removal, and other redox-driven environmental processes via extracellular electron transfer (EET). Unfortunately, developing genotype-phenotype relationships for electroactive organisms is challenging because EET is necessarily removed from the cell of origin. Microdroplet emulsions, which encapsulate individual cells in aqueous droplets, have been used to study a variety of extracellular phenotypes but have not been applied to investigate EET. Here, we describe the development of a microdroplet emulsion system to sort and enrich EET-capable organisms from complex populations. We validated our system using the model electrogen
Shewanella oneidensis
and described the tooling of a benchtop microfluidic system for oxygen-limited conditions. We demonstrated the enrichment of strains exhibiting electroactive phenotypes from mixed wild-type and EET-deficient populations. As a proof-of-concept application, we collected samples from iron sedimentation in Town Lake (Austin, TX) and subjected them to microdroplet enrichment. We measured an increase in electroactive organisms in the sorted population that was distinct compared to a population growing in bulk culture with Fe(III) as the sole electron acceptor. Finally, two bacterial species not previously shown to be EET-capable,
Cronobacter sakazakii
and
Vagococcus fessus
, were further cultured and characterized for electroactivity. Our results demonstrate the utility of microdroplet emulsions for isolating and identifying EET-capable bacteria.

IMPORTANCE

This work outlines a new high-throughput method for identifying electroactive bacteria from mixed populations. Electroactive bacteria play key roles in iron trafficking, soil remediation, and pollutant degradation. Many existing methods for identifying electroactive bacteria are coupled to microbial growth and fitness—as a result, the contributions from weak or poor-growing electrogens are often muted. However, extracellular electron transfer (EET) has historically been difficult to study in high-throughput in a mixed population since extracellular reduction is challenging to trace back to the parent cell and there are no suitable fluorescent readouts for EET. Our method circumvents these challenges by utilizing an aqueous microdroplet emulsion wherein a single cell is statistically isolated in a pico- to nano-liter-sized droplet. Then, via fluorescence obtained from copper reduction, the mixed population can be fluorescently sorted and gated by performance. Utilizing our technique, we characterize two previously unrecognized weak electrogens
Vagococcus fessus
and
Cronobacter sakazakii
.
Extracutaneous sporotrichosis
Authors: Ramírez-Soto Max Carlos 
Published: January 2025

SUMMARY
Sporotrichosis is a subacute-to-chronic infection endemic to tropical and subtropical regions. It usually involves subcutaneous tissue but can occasionally cause extracutaneous infections, especially in hyperendemic areas. Extracutaneous infections are classified based on the anatomic location of the lesion and the route of infection (primary or multifocal). The clinical forms are as follows: (i) pulmonary (primary or multifocal); (ii) osteoarticular (primary or multifocal); (iii) ocular (ocular adnexal lesions including eyelid lesions, conjunctivitis and dacryocystitis, and intraocular infections); (iv) central nervous system; and (v) mucosal (primary or disseminated). Multifocal clinical presentations are observed mainly in immunocompromised individuals. The diagnosis must be confirmed in the laboratory by mycological examination of the clinical samples. Itraconazole and amphotericin B are the most commonly used antifungal agents for treating pulmonary, osteoarticular, ocular, and mucosal forms. Treatment may include surgical excision of the initial lesions in pulmonary and osteoarticular forms. The treatment of neurological involvement is far from optimal and is associated with a high mortality rate despite long treatment periods.
Reverse transcriptase inhibitors diminish systemic proinflammatory responses to bacterial pathogens
Authors: Hullahalli Karthik , Dailey Katherine G. , Acbay Ryan , Suzuki Masataka , Balazs George I. , Waldor Matthew K. 
Published: January 2025

ABSTRACT

Bacterial infections can induce exuberant immune responses that can damage host tissues. Previously, we demonstrated that systemic
Escherichia coli
infection in mice causes tissue damage in the liver. This liver necrosis is associated with the expression of endogenous retroviruses, chromosomally integrated retroviruses that encode a reverse transcriptase. Furthermore, nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs) completely prevent tissue damage and subsequent bacterial growth within necrotic lesions. Since liver necrosis is linked to heightened systemic inflammatory responses, we hypothesized that NRTIs diminish inflammation caused by
E. coli
infection and may also have broad impacts on the systemic immune response to bacterial pathogens. Here, we tested this hypothesis by characterizing the effects of NRTIs on the innate immune response to bacteria. In the liver, NRTI administration following
E. coli
inoculation reduced the expression of a large repertoire of proinflammatory transcripts. NRTIs also had systemic anti-inflammatory effects, including reducing proinflammatory cytokine levels in serum in response to
E. coli
in different mouse strains. The anti-inflammatory effects of NRTIs were also apparent in response to lipopolysaccharide (LPS) and
Staphylococcus aureus
, suggesting that the molecular mechanisms underlying the immunomodulatory functions of NRTIs are likely conserved across distinct immune signaling pathways. Moreover, in a model of lethal LPS shock, NRTI administration prevented hypothermia and death. Together, our observations reveal that NRTIs can potently impede systemic inflammatory responses during Gram-positive and Gram-negative bacterial infections. Our findings lay the groundwork for further investigation of the therapeutic scope of NRTIs and the mechanisms underlying their anti-inflammatory effects across non-retroviral infectious diseases.

IMPORTANCE
Inflammatory responses are critical for host control of bacterial infection, but excessive inflammation can damage host tissues and lead to sepsis. Understanding how innate immune responses are controlled during infection is important for developing new approaches to dampen excessive inflammation. In previous work, we found that tissue damage caused by excessive inflammatory responses may be driven by endogenous reverse transcriptases. Here we demonstrate that treatment of mice with reverse transcriptase inhibitors leads to broad reductions in systemic proinflammatory responses during bacterial infections and can protect mice from acute death in a lethal model of sepsis. Our findings indicate that uncovering the mechanisms underlying the anti-inflammatory functions of reverse transcriptase inhibitors may lead to new therapeutics for bacterial infectious diseases.
Virulence factor discovery identifies associations between the Fic gene family and Fap2
+
fusobacteria in colorectal cancer microbiomes
Authors: Nakatsu Geicho , Ko Duhyun , Michaud Monia , Franzosa Eric A. , Morgan Xochitl C. , Huttenhower Curtis , Garrett Wendy S. 
Published: January 2025

ABSTRACT

Fusobacterium
is a bacterium associated with colorectal cancer (CRC) tumorigenesis, progression, and metastasis. Fap2 is a fusobacteria-specific outer membrane galactose-binding lectin that mediates
Fusobacterium
adherence to and invasion of CRC tumors. Advances in omics analyses provide an opportunity to profile and identify microbial genomic features that correlate with the cancer-associated bacterial virulence factor Fap2. Here, we analyze genomes of
Fusobacterium
colon tumor isolates and find that a family of post-translational modification enzymes containing Fic domains is associated with Fap2 positivity in these strains. We demonstrate that Fic family genes expand with the presence of Fap2 in the fusobacterial pangenome. Through comparative genomic analysis, we find that Fap2
+
Fusobacteriota are highly enriched with Fic gene families compared to other cancer-associated and human gut microbiome bacterial taxa. Using a global data set of CRC shotgun metagenomes, we show that fusobacterial Fic and Fap2 genes frequently co-occur in the fecal microbiomes of individuals with late-stage CRC. We further characterize specific Fic gene families harbored by Fap2
+
Fusobacterium animalis
genomes and detect recombination events and elements of horizontal gene transfer via synteny analysis of Fic gene loci. Exposure of a
F. animalis
strain to a colon adenocarcinoma cell line increases gene expression of fusobacterial Fic and virulence-associated adhesins. Finally, we demonstrate that Fic proteins are synthesized by
F. animalis
as Fic peptides are detectable in
F. animalis
monoculture supernatants. Taken together, our study uncovers Fic genes as potential virulence factors in Fap2
+
fusobacterial genomes.

IMPORTANCE

Accumulating data support that bacterial members of the intra-tumoral microbiota critically influence colorectal cancer progression. Yet, relatively little is known about non-adhesin fusobacterial virulence factors that may influence carcinogenesis. Our genomic analysis and expression assays in fusobacteria identify Fic domain-containing genes, well-studied virulence factors in pathogenic bacteria, as potential fusobacterial virulence features. The Fic family proteins that we find are encoded by fusobacteria and expressed by
Fusobacterium animalis
merit future investigation to assess their roles in colorectal cancer development and progression.
Variable surface antigen expression, virulence, and persistent infection by
Plasmodium falciparum
malaria parasites
Authors: Hadjimichael Evi , Deitsch Kirk W. 
Published: January 2025

SUMMARY

The human malaria parasite
Plasmodium falciparum
is known for its ability to maintain lengthy infections that can extend for over a year. This property is derived from the parasite’s capacity to continuously alter the antigens expressed on the surface of the infected red blood cell, thereby avoiding antibody recognition and immune destruction. The primary target of the immune system is an antigen called PfEMP1 that serves as a cell surface receptor and enables infected cells to adhere to the vascular endothelium and thus avoid filtration by the spleen. The parasite’s genome encodes approximately 60 antigenically distinct forms of PfEMP1, each encoded by individual members of the multicopy
var
gene family. This provides the parasite with a repertoire of antigenic types that it systematically cycles through over the course of an infection, thereby maintaining an infection until the repertoire is exhausted. While this model of antigenic variation based on
var
gene switching explains the dynamics of acute infections in individuals with limited anti-malarial immunity, it fails to explain reports of chronic, asymptomatic infections that can last over a decade. Recent field studies have led to a re-evaluation of previous conclusions regarding the prevalence of chronic infections, and the application of new technologies has provided insights into the molecular mechanisms that enable chronic infections and how these processes evolved.
Near-complete genome sequence of a type-A deformed wing virus discovered from
Solenopsis invicta
in Mississippi, USA
Authors: Liu Xiaofen , Miles Godfrey , Zhu Yu-cheng , Grodowitz Michael , Amiri Esmaeil , Scheffler Brian , Chen Jian 
Published: January 2025

ABSTRACT

Deformed wing virus (DWV) can cause a major disease in honeybees worldwide and has been detected in many other arthropods (S. J. Martin and L. E. Brettell, Annu Rev Virol 6:49–69, 2019,
https://www.annualreviews.org/content/journals/10.1146/annurev-virology-092818-015700
). The presence and replication of DWV in
Solenopsis invicta
(red fire ant) were confirmed (G. P. Miles, X. F. Liu, E. Amiri, M. J. Grodowitz, et al., Insects 14:788, 2023,
https://www.mdpi.com/2075-4450/14/10/788
). Here, we document the DWV-A near-complete genome sequence from
S. invicta
in Mississippi, USA.
Multi-omics investigation of
Porphyromonas gingivalis
exacerbating acute kidney injury through the gut-kidney axis
Authors: Dong Ling , Ji Zhaoxin , Sun Jing , Hu Jiangqi , Jiang Qingsong , Wei Wei 
Published: January 2025

ABSTRACT

Periodontitis is closely related to renal health, but the specific influence of
Porphyromonas gingivalis
(
P. gingivalis
), a key pathogen in periodontitis, on the development of acute kidney injury (AKI) in mice has not been fully elucidated. In our study, AKI was induced in mice through ischemia-reperfusion injury while administering oral infection with
P. gingivalis
. Comprehensive analyses were conducted, including 16S rRNA sequencing, liquid chromatography-mass spectrometry (LC-MS) metabolomics, and transcriptome sequencing.
In vitro
, the identified metabolite was used to stimulate mouse neutrophils. Subsequently, these modified neutrophils were co-cultured with mouse renal tubular epithelial cells. The results showed that oral infection with
P. gingivalis
significantly exacerbated AKI in mice. 16S rRNA sequencing revealed notable shifts in gut microbiota composition. LC-MS metabolomics analysis identified significant metabolic alterations, particularly the upregulation of 3-indoleacrylic acid in the serum. Transcriptome sequencing showed an increased expression of neutrophilic granule protein (
Ngp
), which was closely associated with 3-indoleacrylic acid, and the presence of
Porphyromonas
. Cellular experiments demonstrated that 3-indoleacrylic acid could activate neutrophils, leading to an elevation in NGP protein levels, a response that was associated with renal epithelial cell injury. Oral infection with
P. gingivalis
exacerbated AKI through the gut-kidney axis, involving gut microbiota dysbiosis, metabolic disturbances, and increased renal expression of
Ngp
.

IMPORTANCE

This study provides novel insights into the relationship between periodontal health and renal function.
Porphyromonas gingivalis
oral infection disrupted the balance of gut microbiota and was an important modifier determining the severity of acute kidney injury. Under the “gut-kidney axis,”
P. gingivalis
might cause an increase in the level of the gut microbial metabolite 3-indoleacrylic acid, interfering with kidney immunity and disrupting the maintenance of kidney epithelium.
Trends in
Mycoplasma pneumoniae
infections in pediatric patient preceding, during, and following the COVID-19 pandemic: a comprehensive longitudinal analysis
Authors: Zhang Jianwei , Wu Ruoya , Mo Liyan , Ding Jinlong , Huang Ke 
Published: January 2025

ABSTRACT

This study investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic and its associated restrictive measures on
Mycoplasma pneumoniae
infections in children with acute respiratory tract infection. The study aimed to elucidate the epidemiological characteristics of
M. pneumoniae
infections before and during the pandemic and following the easing of restrictive measures. Pharyngeal secretions were collected from 1,0174 pediatric patients with acute respiratory infection (ARI) who were admitted to Shaoxing Maternity and Child Health Care Hospital (Shaoxing, China) between May 2018 and December 2023. The analysis concentrated on
M. pneumoniae
detection rates, epidemiological features, and clinical characteristics. Among 10,174 samples collected from 2018 to 2023, 1,060 strains of
M. pneumoniae
were detected, resulting in an overall positive rate of 10.42% (
n
= 1,060 out of 1,0176). Further breakdown revealed positive rates of 8.25% (
n
= 279 out of 3,381) in phase I (May 2018–December 2019), 2.40% (
n
= 87 out of 3,623) in phase II (January 2020–November 2022), and 21.89% (
n
= 694 out of 3,170) in phase III (December 2022–December 2023). In comparison to phase I, a noteworthy decline in the positive rate of
M. pneumoniae
was found during phase II, followed by a substantial increase during phase III (
P
< 0.05). Furthermore, the positive rate of
M. pneumoniae
exhibited a significantly greater surge during the summer-autumn period in contrast to the winter-spring (
P
< 0.05). Additionally, the risk of
M. pneumoniae
infection in children who aged 7 years surpassed that of the age group of 0–3 years. Throughout the phases preceding, during, and after the COVID-19 pandemic, discernible fluctuations in both age distribution and seasonality of
M. pneumoniae
infections were identified among hospitalized children with ARI in the East China.

IMPORTANCE

The resemblance between the transmission pathways of
M. pneumoniae
and those of COVID-19 suggests that non-pharmaceutical interventions may have comparable effects on both. This study aimed to analyze the epidemiological characteristics of children with
M. pneumoniae
infections in Shaoxing, China, from 2018 to 2023. This study explored how the COVID-19 pandemic has influenced the prevalence of
M. pneumoniae
and provided guidance for disease treatment and infection prevention.
Impact of gut microbial diversity on egg production performance in chickens
Authors: Wu Liping , Zhang Tao , Luo Zhihua , Xiao Huiyuan , Wang Di , Wu Cailong , Fang Xinyan , Li Jiawei , Zhou Jing , Miao Junjie , Tan Hongli , Wang Yanan , Liu Qing , Huang Jianhua 
Published: January 2025

ABSTRACT

Chickens are one of the most economically important poultry species, and their egg-laying performance is a crucial economic trait. The intestinal microbiome plays a significant role in the egg-laying performance. To clarify the diversity of chicken intestinal microbiota and its connection to egg-laying performance, this study utilized 16S rRNA sequencing technology to characterize the intestinal microbiomes of 101 chickens from 13 breeds with varying levels of egg production. The results reveal significant differences in gut microbiota structure among chicken groups with varying egg production levels. High egg-producing chickens showed significantly higher abundances of
Firmicutes
,
Proteobacteria
, and
Lactobacillus
, while low egg-producing chickens displayed greater microbial α-diversity and more complex community structures. These differences in gut microbiota influence key physiological functions, including nutrient absorption and hormone regulation through metabolic pathways, and directly affect egg production performance. The low and medium production groups partially overlapped on the principal coordinates analysis plot, whereas the high-production group was distinctly separate. This study provides a scientific basis and intestinal microbiome data for selecting probiotics related to high egg production in chickens.

IMPORTANCE

This study elucidates the critical role of gut microbiota in the egg-laying performance of chickens, a key economic indicator in the poultry industry. By employing 16S rRNA sequencing, we uncovered distinct microbial profiles associated with varying levels of egg production. High egg-producing chickens exhibit a higher abundance of specific bacterial taxa, such as
Firmicutes
and
Proteobacteria
, which are linked to enhanced nutrient absorption and metabolic efficiency. Conversely, lower and medium egg-producing chickens display greater microbial diversity, suggesting a more complex but less efficient gut ecosystem. Our findings provide valuable insights into the relationship between gut microbiota and egg production, offering a scientific foundation for the selection of probiotics that could potentially improve the egg-laying performance of chickens. This research not only advances our understanding of avian gut microbiology but also has practical implications for optimizing poultry farming practices and enhancing economic outcomes.