Journal of Microbiology Immunology and Infection最新文献

Background: The conserved CCAAT-binding complex (CBC) specifically recognizes and binds to the CCAAT motif present in eukaryotic promoters, thereby controlling gene transcription. In Candida albicans, the CBC cooperates with another transcription factor, Hap43, to regulate iron homeostasis. Moreover, several Hap43-independent functions have also been uncovered. However, the functions of CBC have not been extensively characterized.

Methods: Deletion mutants lacking each component of the CBC were independently compared to the wild-type strain with regard to cell wall properties, composition, and structure. The effects of CBC deletion on biofilm formation were also investigated. Finally, RNA-seq analysis was performed to reveal functional divergence between the two Hap3 paralogs, Hap31 and Hap32.

Results: CBC deletion significantly impacts cell wall properties, composition, exposure of glucan and chitin, as well as cell wall remodeling. These effects appear to be associated with the small GTPase Rhb1 and the Mkc1 signaling pathway. Moreover, we showed that CBC deletion affects biofilm formation, which appears to be independent of Rhb1. RNA-seq analysis further revealed the broad roles of the Hap3 paralogs within the CBC.

Conclusion: Notably, this work provides new insights into the relationship among CBC, cell wall maintenance, and biofilm formation in C. albicans.

Purpose: Short-term dexamethasone has been used in patients with chronic hepatitis B flares to reduce inflammation in the liver. We aim to identify the potential population that may benefit from dexamethasone treatment.

Methods: A retrospective cohort study was conducted involving 856 hospitalized hepatitis B e antigen-positive patients with chronic hepatitis B flares. The primary endpoint was the 1-year incidence of hepatitis B surface antigen (HBsAg) sero-clearance after the hospital admission. The hazard ratio (HR) and 95 % confidence interval (CI) were calculated using the Cox proportional hazards regression model.

Results: Dexamethasone treatment was associated with a higher incidence of HBsAg sero-clearance (adjusted HR: 3.561, 95 % CI: 1.281-9.902, P = 0.015). These results were further confirmed using the propensity score matching method (HR: 13.115, 95 % CI: 1.705-100.886, P = 0.013). In addition, a faster total bilirubin decrease was observed under dexamethasone treatment (0.57 × upper limit of normal [ULN] per day vs. 0.11 × ULN per day, P < 0.001). Importantly, patients with alanine aminotransferase (ALT) ≥ 30 × ULN and platelet counts ≥ 110 × 10⁹/L were identified as the beneficial population for dexamethasone treatment. These patients showed a higher incidence of HBsAg sero-clearance (39.3 % vs. 11.3 %, P < 0.001; HR: 5.524, 95 % CI: 1.192-25.607, P = 0.029), and faster total bilirubin decline.

Conclusion: Our study confirmed the beneficial role of low-dose and short-term dexamethasone treatment in flare patients, particularly in patients with ALT ≥ 30 × ULN and platelet counts ≥ 110 × 10⁹/L.

Background: Mycobacterium kansasii complex (MKC) is the second common slowly growing mycobacterium associated with pulmonary diseases, typically presenting as chronic, progressive respiratory symptoms with structural lung damage. This study aimed to identify the prognostic factors, genotypes, antimicrobial susceptibility, and treatment outcomes in patients with MKC pulmonary disease (MKC-PD).

Methods: This retrospective cohort study of patients with MKC-PD from January 2016 to August 2021 was conducted at Linkou Chang Gung Memorial Hospital in Taiwan. Diagnosis was based on the 2020 American Thoracic Society/European Respiratory Society/European Society of Clinical Microbiology and Infectious Diseases/and Infectious Diseases Society of America criteria. Medical records were reviewed for demographic data, antimycobacterial agents, and treatment outcomes. Speciation was based on heat-shock protein 65 (hsp65) or Tu elongation factor (tuf) gene sequencing for MKC. Antimicrobial susceptibility was determined using Sensititre RAPMYCO2 broth microdilution.

Results: A total of 202 isolates, one from each patient, were included in the analysis. Sixty-six patients did not meet the diagnostic criteria for MKC-PD, and 71 underwent clinical monitoring without antimycobacterial therapy. Of 65 treated patients, 30 (46.2 %) achieved treatment success, whereas 35 (53.8 %) were categorized as treatment failure. Logistic regression analysis identified age, body mass index (BMI), and treatment duration as significant predictors of treatment outcomes. Of 33 rifampin-resistant strains, 21(63 %) were identified as Mycobacterium persicum.

Conclusions: In this cohort of patients with MKC-PD, treatment outcomes were significantly associated with age, BMI, and treatment duration. These findings underscored the importance of early individualized risk stratification to improve treatment outcomes in MKC-PD.

Background: Although high-dose daptomycin (≥8 mg/kg) and linezolid are recommended treatments for vancomycin-resistant Enterococci (VRE) bloodstream infection (BSI), direct comparisons and the impact of achieving prespecified pharmacokinetic/pharmacodynamic (PK/PD) target on outcomes remain unclear.

Methods: We conducted a retrospective observational study in a single health system (January 2010-December 2021). Patients receiving daptomycin ≥8 mg/kg or linezolid for VRE BSI were included. The primary outcome was in-hospital mortality. The free area under the concentration-time curve to minimum inhibitory concentration ratio (fAUC/MIC) was estimated to assess its association with outcomes.

Results: Overall, 795 patients met the inclusion criteria. The overall mortality was 59.2 %. The linezolid group (n = 170) had a mortality of 44 %, and the daptomycin group (n = 625) mortality was 63 % (P < 0.001). Among daptomycin-treated patients, 528 had fAUC/MIC data and 114 achieved the PK/PD target. Mortality was 66 % for fAUC/MIC ≤75.07 (P < 0.001) and 49 % for fAUC/MIC >75.07 (P = 0.41), compared with linezolid group. In multivariable analysis, daptomycin was associated with higher mortality than linezolid (adjusted odds ratio [aOR], 2.00; P < 0.001). However, failing to achieve PK/PD target conferred significantly higher mortality than linezolid (aOR, 2.51; P < 0.001), whereas achieving the PK/PD target showed no difference (aOR, 0.97; P = 0.91).

Conclusions: Even at doses ≥8 mg/kg, the efficacy for daptomycin is comparable to linezolid only when the PK/PD target is reached. Failing to achieve PK/PD target leads to worse outcomes, underscoring the importance of dose optimization and therapeutic drug monitoring.

Background: Mycobacterium abscessus (MABS) is a clinically significant nontuberculous mycobacterium, and its drug resistance poses substantial therapeutic challenges. Comprehensive genomic and phenotypic analyses are essential for elucidating the mechanisms underlying this resistance and enhancing understanding of its epidemiology.

Methods: Whole-genome sequencing (WGS) using the Illumina platform was conducted on 61 clinical MABS isolates obtained from patients in Thailand. MABS subspecies classification was performed using FastANI, TYGS, and NTM-Profiler. Phenotypic drug susceptibility testing (pDST) was determined using a broth microdilution method. Resistance mutations were identified through NTM-Profiler and Snippy pipelines.

Results: The analysis classified MABS isolates into three subspecies: subsp. abscessus (40/61, 65.57 %), subsp. massiliense (15/61, 24.59 %), and subsp. bolletii (6/61, 9.83 %). Phylogenetic analysis revealed genetic diversity among the majority of the MABS clinical isolates. These isolates clustered into distinct clades, separate from globally recognized clinical strains and dominant circulating clones. Inducible clarithromycin resistance was detected in 60.66 % of MABS isolates, associated with the T28 variant in erm(41). The Ile80Val mutation in erm(41) was significantly associated with inducible clarithromycin resistance (χ² = 12.61, p < 0.001). Acquired clarithromycin resistance associated with rrl mutations (A2270C, A2270G, A2271C) and amikacin resistance linked to the rrs mutation A1375G were detected in 11.48 % and 4.92 % of isolates, respectively. The categorical agreement between WGS-based DST and pDST was 95.08 %, 88.33 %, and 96.43 % for inducible clarithromycin, clarithromycin, and amikacin, respectively.

Conclusion: This study provides valuable insights into the genomic diversity and antimicrobial resistance of MABS isolates in Thailand, emphasizing regional variations in dominant clones and resistance mechanisms.

Background: The new nomenclature of steatotic liver disease (SLD) was proposed in June 2023. The effects of cardiometabolic risk factors (CMRFs) on liver-related events (LREs) in patients achieving chronic hepatitis C (CHC) eradication are unknown.

Methods: This study recruited 1185 patients cured of CHC. CMRFs and alcohol consumption were clearly defined. Variables obtained at 12 or 24 weeks after direct-acting antiviral therapy (PW12) were used to identify the predictors of LREs.

Results: A total of 562 patients (47.4 %) had metabolic dysfunction-associated SLD (MASLD), 96 (8.1 %) had MASLD with increased alcohol intake, 14 (1.2 %) had alcohol-related liver disease, 78 (6.6 %) had cryptogenic SLD, and 435 (36.7 %) had no SLD. Multivariable Cox regression analysis indicated that age, alcohol consumption, per CMRF (hazard ratio: 1.332, 95 % confidence interval: 1.094-1.621), posttreatment albumin level, alpha-fetoprotein level, and fibrosis-4 index >3.25 were independent predictors of LREs. Another multivariable analysis revealed that prediabetes and diabetes mellitus were predictors of LREs.

Conclusions: The new fatty liver disease nomenclature of SLD was used to stratify the risk of LREs in patients achieving CHC eradication. The risk of LREs increased by 33 % per CMRF, and prediabetes or DM was a predictor of LREs.

Background: Persistent chronic hepatitis B virus (HBV) infection leads to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The immunosuppressive tissue microenvironment in the liver restricts the immune response, potentially facilitating persistent HBV infection. This study examined the expression of immunity-related factors in the liver in response to HBV.

Methods: We performed gene expression profiling on mice subjected to HBV DNA hydrodynamic transfection to identify transcriptomic changes. The expression of IL-27 was validated through Western blotting, ELISA, and immunohistochemical staining. Liver macrophages in mice were depleted using clodronate-liposomes to evaluate their role in IL-27 production. IL-27 knockout mice were generated to examine the effects of IL-27 deficiency on CD8 T cell dysfunction and HBV persistence.

Results: Transcriptomic analysis demonstrated that IL-27 is significantly induced in the liver in response to HBV DNA. The elevated levels of IL-27 are strongly correlated with HBV persistence and are linked to CD8 T cell dysfunction, characterized by increased expression of PD-1 and Tim-3, along with reduced IFN-γ production in liver-infiltrating T cells. Furthermore, depleting macrophage-lineage cells using clodronate-liposomes significantly reduces IL-27 production in the liver and promotes viral clearance. Additionally, mice with IL-27 deficiency exhibit enhanced HBV clearance and restored CD8 T cell function.

Conclusions: Collectively, IL-27 is significantly induced by HBV in the liver, and its production is strongly associated with HBV persistence and CD8 T cell dysfunction. This highlights the immunosuppressive role of IL-27 in the liver microenvironment and suggests that IL-27 could serve as a potential therapeutic target for HBV infection.

Background: Coronavirus disease 2019 (COVID-19) remains a public health concern even after its pandemic status officially ended on May 5, 2023, when XBB became the globally predominant SARS-CoV-2 variant. Amid population immunity, the benefit of the monovalent XBB.1.5 vaccines remains uncertain.

Methods: This systematic review searched PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials through November 30, 2024, for studies evaluating the effectiveness of XBB.1.5 vaccines in adults during the 2023-2024 season. Meta-analyses were conducted using a random-effects model (PROSPERO registration: CRD42024513730).

Results: Twenty-one eligible studies, with a total of 53,396,781 participants, were included. Vaccine effectiveness (VE) in the first month post-vaccination was 52.9 % (95 % CI: 47.6 %-57.6 %) against SARS-CoV-2 infection, 64.4 % (95 % CI: 59.3 %-68.9 %) against COVID-19-related hospitalization, and 77.3 % (95 % CI: 67.1 %-84.3 %) against COVID-19-related death. However, by the fifth month, VE declined to 26.7 %, 52.3 %, and 69.4 %, respectively. Notably, against the JN.1 variant that replaced XBB in December 2023, VE against infection, hospitalization, and death dropped significantly by 47 % (from 53.7 % to 28.3 %), 32 % (from 67.8 % to 46.2 %), and 26 % (from 77.3 % to 57.1 %), respectively. VE against hospitalization in individuals aged >60 years was not inferior to that in those aged <60 years (57.2 % versus 49.2 %; subgroup difference, p = 0.24).

Conclusion: XBB.1.5 vaccines provided substantial protection against severe COVID-19 outcomes in the 2023-2024 season prior to the emergence of the JN.1 variant. These findings underscore the need for updated COVID-19 vaccinations to maintain protection against evolving SARS-CoV-2 variants.

Chikungunya virus (CHIKV) infection is the second most widespread arboviral disease after dengue, and a significant number of patients suffer from a spectrum of chronic symptoms. Our objective was to estimate the prevalence of chronic CHIKV infection and its impact on the quality of life of patients. This cross-sectional study was carried out during the CHIKV epidemic in Colombia. For the diagnosis of CHIKV infection, clinical and laboratory criteria were used. Chronic CHIKV infection was defined as a persistence of symptoms after 3 months of the acute episode and health-related quality of life was measured using the Short Form- 36 Health Survey. We selected 290 patients with clinical criteria for CHIKV infection, 172 had positive IgG test anti-CHIKV and were analyzed in the study. The mean age of patients was 43.2 years (SD = 15.4), 128 (74.4 %) were female. Chronic CHIKV infection was documented in 149 (86.6 %, 95 %CI 80.9-91.1). The most frequent symptom was persistent join pain in 94.0 % and affected more frequently knees (67.8 %) and ankles (65.1 %). The SF-36 showed lower values in physical and mental summaries in chronic CHIKV infection compared with non-chronic disease (p value < 0.001). These results show that chronic CHIKV infection is common after an acute episode of CHIKV infection and has a significant impact on the physical and mental health of patients. Health systems must be prepared to adequately identify and care for this population.