Microbiology and Immunology最新文献

Chromoblastomycosis (CBM) is a chronic skin and subcutaneous infection mainly caused by Fonsecaea pedrosoi, a dematiaceous fungus with various morphotypes. Characteristic sclerotic cells-globe-shaped, multiseptated and pigmented-are found in lesions of infected individuals, though their differentiation in the host remains poorly understood. To evaluate in vitro activity of five antifungal drugs-itraconazole (ITZ), posaconazole (PCZ), voriconazole (VCZ), fluconazole (FCZ), and caspofungin (CAS)-against Fonsecaea spp. conidia or sclerotic cells, assessing their minimum inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) and correlated the ITZ MIC with patients' clinical evolution. Forty-three clinical isolates of Fonsecaea spp. and the F. pedrosoi strain ATCC 46428 were assessed for susceptibility to ITZ, PCZ, VCZ, FCZ, and CAS following Clinical Laboratory Standard Institute guidelines (CLSI) (document M38-A2). MIC values were determined after 5 days of incubation at 30°C, followed by MFC determination, with geometric mean MIC (GMMIC) and MFC (GMMFC) used for comparison. PCZ was the most effective antifungal drug, with geometric mean MICs of 0.3 µg/mL (conidia) and 1 µg/mL (sclerotic), and MFCs of 2.98 and 6.72 µg/mL, respectively. Clinical follow-up revealed that higher ITZ MIC values (0.9 µg/mL) correlated with poor patient outcomes compared to lower values in improved or cured patients. These findings highlight PCZ and VCZ as promising options for CBM treatment, especially for patients not responding to ITZ.

Orthohantaviruses are a genus of zoonotic viruses from the family Hantaviridae, which is primarily known for their ability to cause severe human diseases. The virus is primarily known for causing two major human diseases, hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. However, the frequency of this infection remains largely unknown. Hence, the aim of this study was to diagnose patients infected with Orthohantavirus in India. We tested serum samples from 216 febrile patients, presented at Lisie Hospital, Kochi, for positive anti-orthohantavirus IgM and IgG antibodies. All the participating patients were negative for dengue and scrub typhus IgM antibodies. In total, 16.20% (n = 35) of the febrile patients were positive for anti-orthohantavirus IgM and 11.57% (n = 25) for anti-orthohantavirus IgG antibodies. Anti-orthohantavirus IgM and IgG both were detected in 4.63% (n = 10) of the enrolled subjects. In total, 51.43% of the IgM-positive patients had a final diagnosis of either viral fever or acute febrile disease, with only two patients reported to have contact with rodents, and none of these patients had traveled outside of their place of residence. Orthohantavirus infections may be endemic in India, as their hosts are omnipresent. However, the lack of proper diagnostic tools and limited awareness of these emerging infections amongst doctors in India reduces the diagnosis of the disease. Therefore, there is a pressing need for educating healthcare providers about the circulation of orthohantaviruses in India. There is an urgent need for the development of serotype-specific, affordable, and accurate diagnostic tools for early diagnosis of orthohantavirus infections.

HEV causes chronic infections that are detrimental to immunocompromised patients. Previous studies showed alterations of γδ T cell subsets at the acute phase of HEV infection. To assess a possible role of CMV, we have examined the frequencies and responses to CMV and HEV of blood γδ T cell subsets from control donors and acute-phase HEV patients with or without CMV. CMV DNA was mostly undetectable in the blood of CMV-seropositive HEV patients, and anti-CMV antibodies were only slightly elevated. However, Vγ9^negVδ1^pos cells were enriched in vivo, suggesting an increased CMV burden. In contrast, γ9δ1 cells were depleted in most HEV patients, regardless of CMV status. Culturing with IL-2 and IL-15 led to strong γ9δ1 T cell enrichment in samples from HEV patients. After IL-2/IL-15 sensitization, analysis of IFN-γ responses to CMV-infected fibroblasts or hepatocarcinoma cells (with IL-18) showed innate responsiveness to CMV in γ9δ1, γ9δ2, and γ9^negδ1^pos cells in some control subjects and CMV-seronegative patients. However, these responses were selectively exacerbated in CMV-seropositive HEV patients, who also showed significant αβ T cell responses to CMV. This indicates reactivation of anti-CMV immunity. Responses to HEV-infected HepG2 cells remained undetected. IFN-γ responses were not associated with TCR downmodulation in γ9δ2 or γ9^negδ1^pos cells. However, IFN-γ-producing γ9δ1 from HEV patients were characterized by high TCR expression, which was downmodulated after stimulation with CMV-infected fibroblasts or CMV/HEV-coinfected HepG2 cells. We conclude that γ9δ1 T cells are selectively mobilized in HEV patients and can be activated by CMV.

Orthobornaviruses express X and the phosphoprotein (P) from a bicistronic X/P mRNA, and these proteins regulate polymerase activity. In mammalian orthobornaviruses, the 5′ untranslated region (5′ UTR) of the X/P mRNA controls the translational balance between X and P and thereby promotes efficient replication. Avian bornaviruses (ABVs) belong to two clades, clade-2 and -3, that differ in the structure and length of the 5′ UTR of the X/P mRNA. However, the functional consequences of these differences remain unclear. Using reverse genetics, we generated chimeric viruses by reciprocally exchanging the 5′ UTR of the X/P mRNA among clade 2 parrot bornavirus 5 (PaBV-5) and aquatic bird bornavirus 1 (ABBV-1) and clade 3 PaBV-4. In PaBV-5, a long 5′ UTR with a stem–loop and an upstream ORF was required to maintain the X-to-P translational balance. On the other hand, replacing the 5′ UTR of the X/P mRNA from PaBV-5 with that from PaBV-4 reduced X expression and markedly impaired viral growth. However, PaBV-4 tolerated the 5′ UTR of the X/P mRNA from PaBV-5 without detectable effects on translation or replication, which suggests that translation of PaBV-4 X/P mRNA does not depend on the origin of the 5′ UTR. Furthermore, ABBV-1 replicated efficiently with the 5′ UTR of the X/P mRNA from PaBV-5 but was strongly attenuated with that from PaBV-4. Taken together, these results demonstrate a clade-dependent requirement for the 5′ UTR for translation of the X/P mRNA and provide novel insights into the evolution of translational control in orthobornaviruses.

Bordetella has a type III secretion system that secretes virulence proteins crucial to the establishment of infection. The genes encoding components of the Bordetella type III secretion system are located in the bsc region on the chromosome. This region includes the bcrH1 and bcrH2 genes, which respectively encode the proteins BcrH1 and BcrH2. In this study, we analyzed the functions of BcrH1 and BcrH2 in the Bordetella type III secretion system. First, we created a BcrH1-deficient strain and a BcrH2-deficient strain. We analyzed the amounts of the type III secreted proteins BopB and BopD, which make a complex that forms pores in the host membrane, in bacterial cells of each protein-deficient strain. The results showed that the BopB and BopD signals were weakened in the whole cell fraction of the BcrH1-deficient strain and the BcrH2-deficient strain, respectively. The hemolytic activity and cell toxicity of each BcrH protein-deficient strain were significantly lower than those of the wild-type strain. When anti-BcrH1 and anti-BcrH2 antibodies were used for the immunoprecipitation assay, the BopB and BopD signals were detected in the precipitated fractions, respectively. These results strongly suggest that BcrH1 and BcrH2 are specific chaperones for maintaining the stability of BopB and BopD, respectively.

Cover photograph: METTL3 Regulated Skeletal Muscle Atrophy in CKD-Associated Sarcopenia via the TLR4/NF-κB Signaling Pathway. HE staining of kidney and gastrocnemius muscle tissues to assess histopathological changes. Microbiol Immunol: 69:608-618. Article link here

Influenza A and B viruses cause annual epidemics and continue to pose global public health concerns. The most effective approach to preventing or mitigating the severity of influenza is vaccination. Inactivated split influenza HA vaccines are commonly used worldwide due to their strong safety profile and broad range of target groups; however, their efficacy is suboptimal, especially in the elderly. Adjuvants are used to enhance the effectiveness of some influenza vaccines, but few adjuvants have been approved for human vaccines. Previously, we identified hydroxypropyl cellulose as a promising adjuvant for the split influenza HA vaccine for the 2015–2016 and 2016–2017 influenza seasons. Here, we evaluated whether hydroxypropyl cellulose could enhance the efficacy of the quadrivalent split HA vaccine for the 2023–2024 influenza season, which contains the HA proteins of A/Victoria/4897/2022 (H1N1)pdm09 and three other strains. Using a mouse model, we performed immunogenicity studies and assessed protective efficacy against challenges with homologous and heterologous H1N1pdm09 virus strains. We found that hydroxypropyl cellulose in combination with the HA vaccine generated higher virus-specific IgG antibody titers compared to the vaccine alone. The adjuvanted vaccine provided complete protection against homologous challenge and enhanced viral clearance from respiratory organs. Notably, the adjuvanted vaccine demonstrated cross-protective efficacy against heterologous H1N1pdm09 virus challenge, improving survival rates compared to vaccine alone. Our results demonstrate that hydroxypropyl cellulose has potential as an adjuvant for current seasonal influenza vaccines.