Cover photograph: Cover photograph: Radial SUCRA plot of studied adhesion and biofilm-related genes. The size of nodes represents number of isolates used in the network meta-analysis. Microbiol Immunol: 69:104–113. Article link here
Cover photograph: Cover photograph: Radial SUCRA plot of studied adhesion and biofilm-related genes. The size of nodes represents number of isolates used in the network meta-analysis. Microbiol Immunol: 69:104–113. Article link here
COVID-19 severely impacts children in India, with many developing severe pneumonia or multisystem inflammatory syndrome (MIS-C). Concurrently, non-COVID-19 respiratory viruses causing community-acquired pneumonia (CAP) have resurged. These conditions present similarly, challenging accurate diagnosis. This study aims to compare inflammatory markers and clinical parameters in children with severe COVID-19 pneumonia, non-COVID-19 CAP, and COVID-associated MIS-C. We assessed 12 mediators in serum from 14 children with severe COVID-19 pneumonia, 16 with severe non-COVID-19 CAP, and 9 with MIS-C. Clinical characteristics and routine laboratory findings at admission were recorded. Children with MIS-C had significantly higher levels of IL-1RA, IL-8, and TNF compared with those with severe COVID-19 pneumonia; and higher levels of CCL2, HGF, M-CSF, and IL-8 compared with severe non-COVID-19 CAP. GROα levels tended to be higher in severe COVID-19 pneumonia. Clinical presentations were similar, but MIS-C patients had distinct laboratory findings, including lower platelet counts and albumin levels, and higher creatinine and liver enzyme levels. MIS-C exhibited a unique inflammatory profile. IL-8 emerged as a potential biomarker for MIS-C, while increased GROα levels in severe COVID-19 pneumonia merit further exploration. Combining inflammatory markers with routine laboratory parameters may improve the diagnosis and differentiation of these conditions, enhancing patient management.
Yersinia pseudotuberculosis (Ypt) is a gram-negative bacterium that infects both humans and animals primarily through fecal‒oral transmission. While Ypt causes acute gastroenteritis in humans, an association with Kawasaki disease (KD), a disease that primarily affects infants and young children and causes multisystemic vasculitis, has also been suspected. Although KD represents a significant health concern worldwide, the highest annual incidence rate is reported in Japan. Previously, a geographical origin-dependent population structure of Ypt comprising the Asian, transitional, and European clades was proposed. However, genomic data on KD-associated Ypt strains is currently unavailable. In this study, to analyze the phylogenetic and genomic features of KD-associated strains, we determined the whole-genome sequences of 35 Japanese Ypt strains, including 11 KD-associated strains, and constructed a genome set (n = 204) representing the global population of Ypt by adding publicly available Ypt genomes. In a phylogenetic analysis, all sequenced Japanese strains, including the KD-associated strains, belonged to the Asian clade, which appeared to be the ancestral clade of Ypt, and the KD-associated strains belonged to multiple lineages in this clade. Strains from patients with Far East scarlet-like fever (FESLF), a KD-related disease, also belonged to the Asian clade. Moreover, no KD strain-specific genes were identified in pan-genome-wide association study analyses. Notably, however, the gene encoding a superantigen called Yersinia pseudotuberculosis-derived mitogen (YPM) showed a distribution pattern highly biased to the Asian clade. Although further studies are needed, our results suggest that Asian clade strains may have a greater potential to trigger KD.
Infectious mononucleosis (IM) is mainly triggered by Epstein-Barr virus (EBV) infection. There are few studies on the role of the gut microbiota in IM and EBV-associated liver dysfunction. The aim of this study was to investigate the characteristics of the gut microbiota in the EBV-associated liver dysfunction and to evaluate the relationship between the severity of gut microbiota dysbiosis and cytokine levels. A case-control study was performed. Individuals meeting the inclusion and exclusion criteria for EBV-induced IM were enrolled and their fecal and blood samples were collected. The V3-V4 region of the 16s rDNA gene of fecal microbiota was sequenced; bioinformatics analysis including α-diversity, β-diversity, and linear discriminant analysis (LDA) effect size (LEfSe) was performed; and the correlation between bacteria and clinical indices was analysed. A total of 48 participants completed fecal and blood tests, including 18 IM, 11 EBV-associated liver dysfunction, 12 healthy children and 7 EBV-negative liver dysfunction. The α-diversity and β-diversity of the gut microbiota in the EBV-associated liver dysfunction was more than that in IM. The abundance of Granulicatella, Enterococcus, Atopobium and Acinetobacter increased, while the abundance of Prevotella, Sutterella, Collinsella, Desulfovibrio decreased in the EBV-associated liver dysfunction compared with the IM. The abundance of Enterococcus, Atopobium and Acinetobacter correlated positively with the levels of IL-1β, IL-6, TNF-α and CD8+ cytotoxic T lymphocytes%. Gut microbiota of EBV-associated liver dysfunction was significantly disturbed and associated with systemic immune response.
Cover photograph: Retron-Vmi1 is inserted into the dusA gene. Microbiol Immunol: 69:1-9. Article link here
Osteoarthritis (OA) is the most common joint disease and its pathogenic mechanism remains to be ensured. This study focused on the regulatory relation between B-cell lymphoma 6 (BCL6) and G-protein-coupled receptor 61 (GPR61) underlying IL-1β in OA. Real-time quantitative polymerase chain reaction and western blot were performed for mRNA and protein detection. Oxidative injury was assessed by reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) via kits. Fe2+ level was measured via an iron assay kit. Relation analysis between BCL6 and GPR61 was implemented employing ChIP assay and dual-luciferase reporter assay. GPR61 was downregulated in OA samples and IL-1β-induced C28/I2 cells. IL-1β-induced cell inflammation, extracellular matrix (ECM) degradation, oxidative stress, and ferroptosis were all returned by overexpression of GPR61. BCL6 downregulation was detected in OA patients and IL-1β-exposed C28/I2 cells. BCL6 could promote the transcription of GPR61. BCL6 suppressed IL-1β-induced OA progression by upregulating GPR61. The BCL6/GPR61 axis activated the PKA/CREB pathway in IL-1β-treated C28/I2 cells. The above results suggested that BCL6 mitigated OA progression induced by IL-1β by enhancing transcription of GPR61. BCL6/GPR61/PKA/CREB axis may be considered as a novel regulatory mechanism in OA, and BCL6 has the potential to act as a novel target for OA.
Antibiotic-resistant pathogens in public settings present a growing risk to human health. Staphylococcus aureus often asymptomatically colonizes human skin, while virulent strains cause soft tissue infections, osteomyelitis, endocarditis, and are associated with cystic fibrosis. Here we investigated the presence and distribution of multidrug-resistant S. aureus on exercise equipment in university recreation facilities. Equipment sampled included barbells (n = 10), dumbbell handles (n = 15), kettle bell handles (n = 5), ellipticals (n = 5), treadmills (n = 5), cable attachments (n = 5). Mannitol salt agar, CHROMagar-MRSA, Gram staining and latex agglutination testing were useds to isolate and identify S. aureus, including methicillin-resistant S. aureus. Kirby-Bauer disc-diffusion assay was utilized to determine antibiotic susceptibility profiles. Results show 42% of 456 S. aureus isolates from 45 different equipment surfaces were ampicillin resistant. Of 60 representative ampicillin-resistant isolates, 92% were resistant to additional antibiotics with the majority resistant to erythromycin (40%) and sulfisoxazole (75%). Multidrug resistance to three or more drugs was observed in 73% of the ampicillin-resistant subpopulation. These results indicate recreational facilities may serve as reservoirs for multi-drug resistant S. aureus including methicillin-resistant S. aureus (MRSA) and regular disinfection of equipment is warranted for safeguarding public health.
The oral microbiome is closely involved in the maintenance of host health and the development of systemic diseases. The salivary glands play an essential role in homeostasis in the oral cavity. Here, we investigated the effects of periodontal inflammation on salivary gland function and the oral microbiome. In experimental periodontitis model mice, an increase in IgA⁺ cells in the salivary glands were observed 1 week after treatment. Alteration of the oral microbiome was also induced in this model. Gene expression analysis of the salivary glands showed changes in the expression of genes related to B-cell maturation and plasma cell differentiation and an increase in the expression of genes related to macrophage activation upon experimental periodontitis induction. Furthermore, the relationship between disruption of oral microflora and salivary gland function was examined using a cohousing model in which experimental periodontitis model mice and untreated mice were reared in the same cage. We found that cohoused normal mice underwent alteration of the oral microbiome, with increases in IgA⁺ cells and macrophages in the salivary glands. In summary, our results suggest that, in the oral cavity, there is a close link between oral bacterial flora and immune cells in the salivary glands. Our results also show that localized inflammation disrupts the homeostasis in the oral cavity, inducing pathological conditions such as dysbiosis. Our study suggests the importance of the interaction among local oral inflammation, salivary gland function, and oral microflora, and provides new insights into the mechanisms by which oral health is maintained.
Upon infection with the virus, cells increase the expression of cytidine deaminase APOBEC3 family genes. This leads to the accumulation of C-to-T mutations in the replicating viral genome and suppresses viral propagation. In contrast, herpesviruses, including Epstein–Barr virus (EBV), express genes that counteract APOBEC3 during lytic infection. However, because viral resistance factors are not expressed during EBV latent infection, it is unknown how APOBEC3 functions during latent infection. We observed that in gastric epithelial cells persistently infected with EBV, the expression of APOBEC3 family genes increased, C-to-T mutations in the D-loop genome of mitochondrial DNA (mtDNA) increased, and mtDNA copy number decreased. By introducing and expressing individual APOBEC3 family genes, APOBEC3C was particularly expressed in the cytoplasm, increasing C-to-T mutations in mtDNA and decreasing mtDNA copy number. Furthermore, we confirmed that APOBEC3C co-localized with mitochondria in EBV-infected cells. Expression of the EBV latent gene LMP2A increased APOBEC3C expression. Conversely, APOBEC3C expression was reduced in LMP2A-deficient EBV-infected cells compared to wild-type EBV-infected cells. These results indicate that persistent infection of EBV in gastric epithelial cells reduces the number of mitochondria through mtDNA mutations induced by APOBEC3C expression.
The Gram-negative bacteria Bordetella pertussis, B. parapertussis, and B. bronchiseptica cause respiratory diseases in various mammals. They share the BvgAS two-component system, which regulates the phenotypic conversion between the virulent Bvg+ and avirulent Bvg– phases. In the BvgAS system, the sensor kinase BvgS senses environmental cues and transduces a phosphorelay signal to the response regulator BvgA, which leads to the expression of Bvg+ phase-specific genes, including virulence factor genes. Bacteria grown at 37°C exhibit the Bvg+ phenotype. In contrast, at lower than 26°C or in the presence of modulators, such as MgSO4 and nicotinic acid, the BvgAS system is inactivated, leading bacteria to the avirulent Bvg– phase. Therefore, effective modulators are expected to provide a therapeutic measure for Bordetella infection; however, no such modulators are currently available, and the mechanism by which modulators inactivate the BvgAS system is poorly understood. In the present study, we identified lonidamine as a novel modulator after screening an FDA-approved drug library using bacterial reporter systems with the Bvg+-specific and Bvg–-specific promoters. Lonidamine directly bound to the VFT2 domain of BvgS and inactivated the BvgAS system at concentrations as low as 50 nM, which was at least 2000- to 20,000-fold lower than the effective concentrations of known modulators. Lonidamine significantly reduced the adherence of B. pertussis to cultured cells but unexpectedly exacerbated bacterial colonization of the mouse nasal septum. These results provide insights into the structural requirements for BvgAS modulators and the role of Bvg phenotypes in the establishment of infection.
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