Bioinform Adv. 2023 Jul 17;3(1):vbad098. doi: 10.1093/bioadv/vbad098. eCollection 2023.

ABSTRACT

MOTIVATION: Metabolite-protein interactions play an important role in regulating protein functions and metabolism. Yet, predictions of metabolite-protein interactions using genome-scale metabolic networks are lacking. Here, we fill this gap by presenting a computational framework, termed SARTRE, that employs features corresponding to shadow prices determined in the context of flux variability analysis to predict metabolite-protein interactions using supervised machine learning.

RESULTS: By using gold standards for metabolite-protein interactomes and well-curated genome-scale metabolic models of Escherichia coli and Saccharomyces cerevisiae, we found that the implementation of SARTRE with random forest classifiers accurately predicts metabolite-protein interactions, supported by an average area under the receiver operating curve of 0.86 and 0.85, respectively. Ranking of features based on their importance for classification demonstrated the key role of shadow prices in predicting metabolite-protein interactions. The quality of predictions is further supported by the excellent agreement of the organism-specific classifiers on unseen interactions shared between the two model organisms. Further, predictions from SARTRE are highly competitive against those obtained from a recent deep-learning approach relying on a variety of protein and metabolite features. Together, these findings show that features extracted from constraint-based analyses of metabolic networks pave the way for understanding the functional roles of the interactions between proteins and small molecules.

AVAILABILITY AND IMPLEMENTATION: https://github.com/fayazsoleymani/SARTRE.

PMID:37521309 | PMC:PMC10374491 | DOI:10.1093/bioadv/vbad098

iScience. 2023 Jul 3;26(8):107272. doi: 10.1016/j.isci.2023.107272. eCollection 2023 Aug 18.

ABSTRACT

Treatment options for anaplastic thyroid cancer (ATC) and refractory papillary thyroid carcinoma (PTC) are limited and outcomes remain poor. In this study, we determined via bioinformatic expression analyses and immunohistochemistry staining that intercellular adhesion molecule-1(ICAM1) is an attractive target for ATC and PTC. We designed and engineered two ICAM1-directed antibody-drug conjugate (I1-MMAE and I1-DXd), both of which potently and selectively ablate multiple human ATC and PTC cell lines without affecting non-plastic cells in vitro. Furthermore, I1-MMAE and I1-DXd mediated a potent tumor regression in ATC and PTC xenograft models. To develop a precision medicine, we also explored magnetic resonance imaging (MRI) as a non-invasive biomarker detection method to quantitatively map ICAM1 antigen expression in heterogeneous thyroid tumors. Taken together, this study provides a strong rationale for the further development of I1-MMAE and I1-DXd as promising therapeutic candidates to treat advanced PTC and ATC.

PMID:37520726 | PMC:PMC10371847 | DOI:10.1016/j.isci.2023.107272

iScience. 2023 Jul 13;26(8):107367. doi: 10.1016/j.isci.2023.107367. eCollection 2023 Aug 18.

ABSTRACT

Immune checkpoint blockade has become an effective approach to reverse the immune tolerance of tumor cells. Indoleamine 2,3-dioxygenase 1 (IDO1) is frequently upregulated in many types of cancers and contributes to the establishment of an immunosuppressive cancer microenvironment, which has been thought to be a potential target for cancer therapy. However, the development of IDO1 inhibitors for clinical application is still limited. Here, we isolated a DNA aptamer with a strong affinity and inhibitory activity against IDO1, designated as IDO-APT. By conjugating with nanoparticles, in situ injection of IDO-APT to CT26 tumor-bearing mice significantly suppresses the activity of regulatory T cells and promotes the function of CD8+ T cells, leading to tumor suppression and prolonged survival. Therefore, this functional IDO1-specific aptamer with potent anti-tumor effects may serve as a potential therapeutic strategy in cancer immunotherapy. Our data provide an alternative way to target IDO1 in addition to small molecule inhibitors.

PMID:37520707 | PMC:PMC10374466 | DOI:10.1016/j.isci.2023.107367

Front Immunol. 2023 Jul 12;14:1177672. doi: 10.3389/fimmu.2023.1177672. eCollection 2023.

ABSTRACT

BACKGROUND AND OBJECTIVES: Encephalitis is a devastating neurologic disorder with high morbidity and mortality. Autoimmune causes are roughly as common as infectious ones. N-methyl-D-aspartic acid receptor (NMDAR) encephalitis (NMDARE), characterized by serum and/or spinal fluid NMDAR antibodies, is the most common form of autoimmune encephalitis (AE). A translational rodent NMDARE model would allow for pathophysiologic studies of AE, leading to advances in the diagnosis and treatment of this debilitating neuropsychiatric disorder. The main objective of this work was to identify optimal active immunization conditions for NMDARE in mice.

METHODS: Female C57BL/6J mice aged 8 weeks old were injected subcutaneously with an emulsion of complete Freund's adjuvant, killed and dessicated Mycobacterium tuberculosis, and a 30 amino acid peptide flanking the NMDAR GluN1 subunit N368/G369 residue targeted by NMDARE patients' antibodies. Three different induction methods were examined using subcutaneous injection of the peptide emulsion mixture into mice in 1) the ventral surface, 2) the dorsal surface, or 3) the dorsal surface with reimmunization at 4 and 8 weeks (boosted). Mice were bled biweekly and sacrificed at 2, 4, 6, 8, and 14 weeks. Serum and CSF NMDAR antibody titer, mouse behavior, hippocampal cell surface and postsynaptic NMDAR cluster density, and brain immune cell entry and cytokine content were examined.

RESULTS: All immunized mice produced serum and CSF NMDAR antibodies, which peaked at 6 weeks in the serum and at 6 (ventral and dorsal boosted) or 8 weeks (dorsal unboosted) post-immunization in the CSF, and demonstrated decreased hippocampal NMDAR cluster density by 6 weeks post-immunization. In contrast to dorsally-immunized mice, ventrally-induced mice displayed a translationally-relevant phenotype including memory deficits and depressive behavior, changes in cerebral cytokines, and entry of T-cells into the brain at the 4-week timepoint. A similar phenotype of memory dysfunction and anxiety was seen in dorsally-immunized mice only when they were serially boosted, which also resulted in higher antibody titers.

DISCUSSION: Our study revealed induction method-dependent differences in active immunization mouse models of NMDARE disease. A novel ventrally-induced NMDARE model demonstrated characteristics of AE earlier compared to dorsally-induced animals and is likely suitable for most short-term studies. However, boosting and improving the durability of the immune response might be preferred in prolonged longitudinal studies.

PMID:37520559 | PMC:PMC10374403 | DOI:10.3389/fimmu.2023.1177672

Holist Integr Oncol. 2022;1(1):8. doi: 10.1007/s44178-022-00010-z. Epub 2022 Jul 5.

ABSTRACT

PURPOSE: Major public health emergencies may lead to delays or alterations in the treatment of patients with breast cancer at each stage of diagnosis and treatment. How much do these delays and treatment changes affect treatment outcomes in patients with breast cancer?

METHODS: This review summarized relevant research in the past three decades and identified the effect of delayed treatment on the prognosis of patients with breast cancer in terms of seeking medical treatment, neoadjuvant treatment, surgery, postoperative chemotherapy, radiotherapy, and targeted therapies.

RESULTS: Delay in seeking medical help for ≥12 weeks affected the prognosis. Surgical treatment within 4 weeks of diagnosis did not affect patient prognosis. Starting neoadjuvant chemotherapy within 8 weeks after diagnosis, receiving surgical treatment at 8 weeks or less after the completion of neoadjuvant chemotherapy, and receiving radiotherapy 8 weeks after surgery did not affect patient prognosis. Delayed chemotherapy did not increase the risk of relapse in patients with luminal A breast cancer. Every 4 weeks of delay in the start of postoperative chemotherapy in patients with luminal B, triple-negative, or HER2-positive breast cancer treated with trastuzumab will adversely affect the prognosis. Targeted treatment delays in patients with HER2-positive breast cancer should not exceed 60 days after surgery or 4 months after diagnosis. Radiotherapy within 8 weeks after surgery did not increase the risk of recurrence in patients with early breast cancer who were not undergoing adjuvant chemotherapy.

CONCLUSION: Different treatments have different time sensitivities, and the careful evaluation and management of these delays will be helpful in minimizing the negative effects on patients.

PMID:37520334 | PMC:PMC9255457 | DOI:10.1007/s44178-022-00010-z

PeerJ. 2023 Jul 24;11:e15630. doi: 10.7717/peerj.15630. eCollection 2023.

ABSTRACT

The ability of insulin to stimulate glucose transport in muscle and fat cells is mediated by the regulated delivery of intracellular vesicles containing glucose transporter-4 (GLUT4) to the plasma membrane, a process known to be defective in disease such as Type 2 diabetes. In the absence of insulin, GLUT4 is sequestered in tubules and vesicles within the cytosol, collectively known as the GLUT4 storage compartment. A subset of these vesicles, known as the 'insulin responsive vesicles' are selectively delivered to the cell surface in response to insulin. We have previously identified Syntaxin16 (Sx16) and its cognate Sec1/Munc18 protein family member mVps45 as key regulatory proteins involved in the delivery of GLUT4 into insulin responsive vesicles. Here we show that mutation of a key residue within the Sx16 N-terminus involved in mVps45 binding, and the mutation of the Sx16 binding site in mVps45 both perturb GLUT4 sorting, consistent with an important role of the interaction of these two proteins in GLUT4 trafficking. We identify Threonine-7 (T7) as a site of phosphorylation of Sx16 in vitro. Mutation of T7 to D impairs Sx16 binding to mVps45 in vitro and overexpression of T7D significantly impaired insulin-stimulated glucose transport in adipocytes. We show that both AMP-activated protein kinase (AMPK) and its relative SIK2 phosphorylate this site. Our data suggest that Sx16 T7 is a potentially important regulatory site for GLUT4 trafficking in adipocytes.

PMID:37520260 | PMC:PMC10373645 | DOI:10.7717/peerj.15630

Front Genet. 2023 Jul 14;14:1252328. doi: 10.3389/fgene.2023.1252328. eCollection 2023.

NO ABSTRACT

PMID:37519892 | PMC:PMC10382133 | DOI:10.3389/fgene.2023.1252328

Front Genet. 2023 Jul 14;14:1217414. doi: 10.3389/fgene.2023.1217414. eCollection 2023.

ABSTRACT

Targeted therapies and chemotherapies are prevalent in cancer treatment. Identification of predictive markers to stratify cancer patients who will respond to these therapies remains challenging because patient drug response data are limited. As large amounts of drug response data have been generated by cell lines, methods to efficiently translate cell-line-trained predictors to human tumors will be useful in clinical practice. Here, we propose versatile feature selection procedures that can be combined with any classifier. For demonstration, we combined the feature selection procedures with a (linear) logit model and a (non-linear) K-nearest neighbor and trained these on cell lines to result in LogitDA and KNNDA, respectively. We show that LogitDA/KNNDA significantly outperforms existing methods, e.g., a logistic model and a deep learning method trained by thousands of genes, in prediction AUC (0.70-1.00 for seven of the ten drugs tested) and is interpretable. This may be due to the fact that sample sizes are often limited in the area of drug response prediction. We further derive a novel adjustment on the prediction cutoff for LogitDA to yield a prediction accuracy of 0.70-0.93 for seven drugs, including erlotinib and cetuximab, whose pathways relevant to anti-cancer therapies are also uncovered. These results indicate that our methods can efficiently translate cell-line-trained predictors into tumors.

PMID:37519889 | PMC:PMC10382684 | DOI:10.3389/fgene.2023.1217414

Development. 2023 Jul 31:dev.201562. doi: 10.1242/dev.201562. Online ahead of print.

ABSTRACT

Changes in gene expression represent an important source of phenotypic innovation. Yet, how such changes emerge and impact the evolution of traits remains elusive. Here, we explore the molecular mechanisms associated with the development of masculinizing ovotestes in female moles. By performing integrative analyses of epigenetic and transcriptional data in mole and mouse, we identified the co-option of SALL1 expression in mole ovotestes formation. Chromosome conformation capture analyses highlight a striking conservation of the 3D organization at the SALL1 locus, but an evolutionary divergence of enhancer activity. Interspecies reporter assays support the capability of mole-specific enhancers to activate transcription in urogenital tissues. Through overexpression experiments in transgenic mice, we further demonstrate the capability of SALL1 to induce kidney-related gene programs, which are a signature of mole ovotestes. Our results highlight the co-option of gene expression, through changes in enhancer activity, as a plausible mechanism for the evolution of traits.

PMID:37519269 | DOI:10.1242/dev.201562

J Cell Sci. 2023 Jul 31:jcs.261416. doi: 10.1242/jcs.261416. Online ahead of print.

ABSTRACT

Accurate genome segregation in mitosis requires that all chromosomes are bioriented on the spindle. Cells monitor biorientation by sensing tension across sister centromeres. Chromosomes that are not bioriented have low centromere tension, which allows Aurora B (yeast Ipl1) to perform error correction that locally loosens kinetochore-microtubule attachments to allow detachment of microtubules and fresh attempts at achieving biorientation. However, it is not known if low tension recruits Aurora B to centromeres or, alternatively, if low tension directly activates Aurora B already localized at centromeres. In this work, we experimentally induced low tension in metaphase yeast cells, then monitored Ipl1 localization. We find low tension recruits Ipl1 to centromeres. Further, low tension induced Ipl1 recruitment depended on Bub1, which is known to provide a binding site for Ipl1. In contrast, Top2, which can also recruit Ipl1 to centromeres, was not required. Our results demonstrate cells are sensitive to low tension at centromeres and respond by actively recruiting Ip1l for error correction.

PMID:37519149 | DOI:10.1242/jcs.261416

Proteins. 2023 Jul 30. doi: 10.1002/prot.26558. Online ahead of print.

ABSTRACT

Amyloid-based prions have simple structures, a wide phylogenetic distribution, and a plethora of functions in contemporary organisms, suggesting they may be an ancient phenomenon. However, this hypothesis has yet to be addressed with a systematic, computational, and experimental approach. Here we present a framework to help guide future experimental verification of candidate prions with conserved functions to understand their role in the early stages of evolution and potentially in the origins of life. We identified candidate prions in all high-quality proteomes available in UniProt computationally, assessed their phylogenomic distributions, and analyzed candidate-prion functional annotations. Of the 27 980 560 proteins scanned, 228 561 were identified as candidate prions (~0.82%). Among these candidates, there were 84 Gene Ontology (GO) terms conserved across the three domains of life. We found that candidate prions with a possible role in adaptation were particularly well-represented within this group. We discuss unifying features of candidate prions to elucidate the primeval roles of prions and their associated functions. Candidate prions annotated as transcription factors, DNA binding, and kinases are particularly well suited to generating diverse responses to changes in their environment and could allow for adaptation and population expansion into more diverse environments. We hypothesized that a relationship between these functions and candidate prions could be evolutionarily ancient, even if individual prion domains themselves are not evolutionarily conserved. Candidate prions annotated with these universally occurring functions potentially represent the oldest extant prions on Earth and are therefore excellent experimental targets.

PMID:37519023 | DOI:10.1002/prot.26558

Plant Genome. 2023 Jul 30:e20372. doi: 10.1002/tpg2.20372. Online ahead of print.

ABSTRACT

Date palm (Phoenix dactylifera L.) is able to grow and complete its life cycle while being rooted in highly saline soils. Which of the many well-known salt-tolerance strategies are combined to fine-tune this remarkable resilience is unknown. The precise location, whether in the shoot or the root, where these strategies are employed remains uncertain, leaving us unaware of how the various known salt-tolerance mechanisms are integrated to fine-tune this remarkable resilience. To address this shortcoming, we exposed date palm to a salt stress dose equivalent to seawater for up to 4 weeks and applied integrative multi-omics analyses followed by targeted metabolomics, hormone, and ion analyses. Integration of proteomic into transcriptomic data allowed a view beyond simple correlation, revealing a remarkably high degree of convergence between gene expression and protein abundance. This sheds a clear light on the acclimatization mechanisms employed, which depend on reprogramming of protein biosynthesis. For growth in highly saline habitats, date palm effectively combines various salt-tolerance mechanisms found in both halophytes and glycophytes: "avoidance" by efficient sodium and chloride exclusion at the roots, and "acclimation" by osmotic adjustment, reactive oxygen species scavenging in leaves, and remodeling of the ribosome-associated proteome in salt-exposed root cells. Combined efficiently as in P. dactylifera L., these sets of mechanisms seem to explain the palm's excellent salt stress tolerance.

PMID:37518859 | DOI:10.1002/tpg2.20372

Zootaxa. 2023 Jun 8;5301(1):51-74. doi: 10.11646/zootaxa.5301.1.2.

ABSTRACT

Carpophilus truncatus Murray 1864, is a species of sap beetle which has been recorded from many countries worldwide, and has become recognised as an important pest of nuts. In this study, we present a re-description of C. truncatus including diagnostic photographic images of the adults and larvae, and demonstrate that Carpophilus jarijari Powell & Hamilton, 2019 is a junior subjective synonym of C. truncatus. Information about the species' distribution in Australia is updated. DNA barcode sequence data for C. truncatus is reviewed and augmented to enable differentiation from other morphologically similar Carpophilus species that are associated with nuts as hosts, including the cosmopolitan Carpophilus dimidiatus (Fabricius, 1792), for which C. truncatus has sometimes been misidentified. This analysis revealed that existing reference DNA sequences of "C. dimidiatus" consist of three highly genetically divergent lineages, representing three species: the cosmopolitan C. dimidiatus, the widespread C. truncatus, and a newly described species, Carpophilus imitatus sp. nov., known from south-eastern Asia and Australia.

PMID:37518573 | DOI:10.11646/zootaxa.5301.1.2

Zootaxa. 2023 May 4;5278(1):143-154. doi: 10.11646/zootaxa.5278.1.7.

ABSTRACT

Himantariella scutellaris Brolemann, 1926 has previously been considered a French endemic species from the eastern Pyrenees. New collecting data from the Spanish Pre-Pyrenees, the Prelitoral Mountain Range and the Cantabric Region, make it possible to expand its known distribution to the northern Iberian Peninsula. Intraspecific variability, habitat preferences and ethology are assessed for the first time. New figures on the morphology of H. scutellaris and identification keys for the European Himantariidae with terminal pore-fields are provided. Results showed a wider range of morphological variability than previously reported and allowed to update the diagnostic characters needed for identification. Additionally, results showed monticolous, synanthropic and nocturnal habits for the Iberian populations and suggest that H. scutellaris is a common species at a local scale. Finally, morphology and ecology of H. scutellaris from the Iberian Peninsula and the Pyrenees are discussed in depth.

PMID:37518292 | DOI:10.11646/zootaxa.5278.1.7

Trends Microbiol. 2023 Jul 28:S0966-842X(23)00225-1. doi: 10.1016/j.tim.2023.07.013. Online ahead of print.

ABSTRACT

A recent study (Johansen et al., 2023) shows how the ecological composition of the human gut virome changes with age, showing a decline in core taxa and an enrichment of subdominant taxa, similar to what has been observed in the gut bacteriomes of centenarians.

PMID:37517959 | DOI:10.1016/j.tim.2023.07.013

Adv Drug Deliv Rev. 2023 Jul 28:115027. doi: 10.1016/j.addr.2023.115027. Online ahead of print.

ABSTRACT

The rising incidence and persistent thrombosis in multiple cancers including those that are immunosuppressive highlight the need for understanding the tumor coagulome system and its role beyond hemostatic complications. Immunotherapy has shown significant benefits in solid organ tumors but has been disappointing in the treatment of hypercoagulable cancers, such as glioblastoma and pancreatic ductal adenocarcinomas. Thus, targeting thrombosis to prevent immunosuppression seems a clinically viable approach in cancer treatment. Hypercoagulable tumors often develop fibrin clots within the tumor microenvironment (TME) that dictates the biophysical characteristics of the tumor tissue. The application of systems biology and single-cell approaches highlight the potential role of coagulome or thrombocytosis in shaping the tumor immune microenvironment (TIME). In-depth knowledge of the tumor coagulome would provide unprecedented opportunities to better predict the hemostatic complications, explore how thrombotic stroma modulates tumor immunity, reexamine the significance of clinical biomarkers, and enable steering the stromal versus systemic immune response for boosting the effectiveness of immune checkpoint inhibitors in cancer treatment. We focus on the role of coagulation factors in priming a suppressive TIME and the huge potential of existing anticoagulant drugs in the clinical settings of cancer immunotherapy.

PMID:37517779 | DOI:10.1016/j.addr.2023.115027

J Biol Chem. 2023 Jul 28:105107. doi: 10.1016/j.jbc.2023.105107. Online ahead of print.

ABSTRACT

Protein-protein interactions (PPIs) form the foundation of any cell signaling network. Considering that PPIs are highly dynamic processes, cellular assays are often essential for their study because they closely mimic the biological complexities of cellular environments. However, incongruity may be observed across different PPI assays when investigating a protein partner of interest; these discrepancies can be partially attributed to the fusion of different large functional moieties, such as fluorescent proteins or enzymes, which can yield disparate perturbations to the protein's stability, subcellular localization, and interaction partners depending on the given cellular assay. Owing to their smaller size, epitope tags may exhibit a diminished susceptibility to instigate such perturbations. However, while they have been widely used for detecting or manipulating proteins in vitro, epitope tags lack the in vivo traceability and functionality needed for intracellular biosensors. Herein, we develop NbV5, an intracellular nanobody binding the V5-tag, which is suitable for use in cellular assays commonly used to study PPIs such as BRET, NanoBiT, and Tango. The NbV5:V5 tag system has been applied to interrogate G protein-coupled receptor signaling, specifically by replacing larger functional moieties attached to the protein interactors, such as fluorescent or luminescent proteins (∼30kDa), by the significantly smaller V5-tag peptide (1.4kDa), and for microscopy imaging which is successfully detected by NbV5-based biosensors. Therefore, the NbV5:V5 tag system presents itself as a versatile tool for live-cell imaging and a befitting adaptation to existing cellular assays dedicated to probing PPIs.

PMID:37517699 | DOI:10.1016/j.jbc.2023.105107

J Biol Chem. 2023 Jul 28:105111. doi: 10.1016/j.jbc.2023.105111. Online ahead of print.

ABSTRACT

Upon infection by the malaria parasite Plasmodium falciparum, the glycolytic rate of a red blood cell increases up to 100-fold, possibly contributing to lactic acidosis and hypoglycaemia in patients with severe malaria. This dramatic increase in glucose uptake and metabolism was correctly predicted by a newly constructed detailed enzyme kinetic model of glucose metabolism in the trophozoite-infected red blood cell. Subsequently, we expanded the model to simulate an infected red blood cell culture, including the different asexual blood-stage forms of the malaria parasite. The model simulations were in good agreement with experimental data, for which the measured parasitic volume was an important parameter. Upon further analysis of the model, we identified glucose transport as a drug target that would specifically affect infected red blood cells, which was confirmed experimentally with inhibitor titrations. This model can be a first step in constructing a whole-body model for glucose metabolism in malaria patients to evaluate the contribution of the parasite's metabolism to the disease state.

PMID:37517694 | DOI:10.1016/j.jbc.2023.105111

J Cell Biol. 2023 Sep 4;222(9):e202304106. doi: 10.1083/jcb.202304106. Epub 2023 Jul 26.

ABSTRACT

Herpes simplex virus (HSV-1) progeny form in the nucleus and exit to successfully infect other cells. Newly formed capsids navigate complex chromatin architecture to reach the inner nuclear membrane (INM) and egress. Here, we demonstrate by transmission electron microscopy (TEM) that HSV-1 capsids traverse heterochromatin associated with trimethylation on histone H3 lysine 27 (H3K27me3) and the histone variant macroH2A1. Through chromatin profiling during infection, we revealed global redistribution of these marks whereby massive host genomic regions bound by macroH2A1 and H3K27me3 correlate with decreased host transcription in active compartments. We found that the loss of these markers resulted in significantly lower viral titers but did not impact viral genome or protein accumulation. Strikingly, we discovered that loss of macroH2A1 or H3K27me3 resulted in nuclear trapping of capsids. Finally, by live-capsid tracking, we quantified this decreased capsid movement. Thus, our work demonstrates that HSV-1 takes advantage of the dynamic nature of host heterochromatin formation during infection for efficient nuclear egress.

PMID:37516914 | DOI:10.1083/jcb.202304106

Diagn Pathol. 2023 Jul 29;18(1):85. doi: 10.1186/s13000-023-01360-6.

ABSTRACT

A pediatric patient suffered from renal and hepatic abscesses (through hepatorenal space) and recovered by antibiotics and other therapies. By clinical analysis, the multi-organ abscesses might be caused by bloodstream-disseminated infection. In order to identify the pathogen, we collected kidney biopsy tissue, swabs, and plasma samples, and used metagenomics next-generation sequencing (mNGS) and some traditional methods. The results revealed that polymicrobial especially anaerobic bacteremia (Bacteroides fragilis, et al.) contributed to the abscess formation. What is more, systematic human adenovirus C (HAdV-C) infection was shown, and the virus was isolated. The titer of HAdV-2 neutralizing antibodies was 1/4 in the plasma after symptoms onset. Although the exact mechanism of HAdV-2 infection in multiple abscess formation has not been clarified, the case of multi-organ abscesses in the context of polymicrobial especially anaerobic bacteremia and HAdV infection in healthy children is infrequent.

PMID:37516858 | DOI:10.1186/s13000-023-01360-6