Journal of Microbiology Immunology and Infection最新文献

Purpose: This retrospective study aimed to investigate demographic characteristics, predisposing factors, and clinical outcomes in patients with parasitic keratitis.

Methods: Medical records of patients with molecularly confirmed Acanthamoeba or microsporidia, identified through corneal scraping specimens (collected between September 21, 2017, and June 27, 2023), were reviewed. Demographic data, clinical profiles, such as symptom duration before confirmed diagnosis, antiviral treatment pre-diagnosis, contact lens use, tap water and soil contamination, ocular trauma, and treatment regimens, were analyzed.

Results: Fifty PCR-confirmed cases included 35 Acanthamoeba keratitis (AK) and 15 microsporidia keratitis (MK). Of these, 23 males and 27 females, aged 8 to 81, showed a significant difference (p = 0.02) in the distribution of farmers between the AK and MK groups. Mean symptom durations pre-diagnosis were 27.6 days (range: 1-180) in AK and 11.47 days (range: 1-60) in MK. AK cases exhibited a higher prevalence of stromal involvement (p < 0.05) and contact lens use (p < 0.001), while more MK patients had a history of soil contamination (p = 0.016). Univariable analysis linked stromal keratitis, symptom duration, and pre-diagnosis antiviral treatment to prolonged time to stability. In the multivariable model, only symptom duration predicted extended time to stability, with an expected increase of 0.65 days for each additional pre-diagnosis day.

Conclusion: This study underscores the significance of parasitic keratitis in Southern Taiwan, emphasizing the necessity of incorporating PCR as an effective diagnostic tool to enhance the routine identification of these rare conditions, moving beyond reliance on standard conventional methods.

Background: Azole antifungals are the first-line choice for treating candidiasis within a limited antifungal option. However, azole-resistant Candida species have increased rapidly, causing severe clinical threats, especially multidrug-resistant (MDR) isolates. The emergence of Candida auris has also caused global concerns recently.

Methods: Herein, we evaluated the antifungal activity of taurine-induced silver ions (Tau-Ag), prepared by the induction from silver-incorporated mesoporous bioactive glass to address this issue.

Results: Our data demonstrated that minimum inhibitory concentrations (MICs) of Tau-Ag ranged from 0.020 to 0.078 mg/mL in 24h and from 0.039 to 0.156 mg/mL in 48h. No hemolysis and cytotoxicity were observed at the MICs. Furthermore, no in vivo toxicity related to Tau-Ag was observed in a Caenorhabditis elegans model. In the investigation of antifungal mechanisms, we observed that the reactive oxygen species (ROS) level significantly increased when Candida spp. treated with Tau-Ag. Biofilm formation inhibition assays found that Tau-Ag may penetrate the biofilm and eliminate biofilm-forming cells. In the time-kill method, Tau-Ag showed a long-lasting fungistatic effect and superior antifungal effect compared to itraconazole alone. Furthermore, Tau-Ag showed synergistic antifungal effects in combination with itraconazole, effectively restoring its activity.

Conclusion: Our results confirmed the potential of Tau-Ag and its combination use with itraconazole to serve as a novel antifungal agent to combat the plight of administration on azole-resistant and MDR Candida spp. and C. auris.

Objectives: The aim of this study was to assess the clinical utility of metagenomic next-generation sequencing (mNGS) and metagenomic third-generation sequencing (mTGS) in diagnosing cervical lymph node tuberculosis through analysis of lymph node tissue.

Methods: This study recruited 101 patients with suspected cervical lymph node tuberculosis and took samples under ultrasound guidance. Parallel culture, X-pert, mNGS and mTGS workflows to each sample were performed. Taking clinical diagnosis as the gold standard, We comparatively compared diagnosis performance of the four methods.

Results: Clinically, 76 cases were diagnosed as lymph node tuberculosis and 20 cases were non-lymph node tuberculosis. Compared with clinical diagnosis, the sensitivities of mNGS and mTGS were 89.47 % and 82.89 %, respectively, significantly higher than those of culture and X-pert which were 43.28 % and 68.42 %, respectively (P < 0.05). The specificity of mNGS and X-pert reached 100 %, while those of culture and mTGS were 93.75 % and 95 %, respectively. And mNGS alone identified 7 species of bacteria, 3 species of viruses, and 5 species of fungi, and identified more mixed infections. Particularly, besides Mycobacterium tuberculosis detection, mNGS may be superior to mTGS for the detection of fungi. Pathogen identification of mNGS and mTGS is less affected by previous anti-tuberculosis drug usage.

Conclusion: mNGS and mTGS play a crucial role in the rapid diagnosis and accurate treatment on Cervical lymph node tuberculosis.

Background: Aeromonas infections pose a significant threat associated with high mortality rates. This study investigates the potential of mitomycin C (MMC), an anticancer drug, as a novel antimicrobial agent against Aeromonas infections.

Methods: We evaluated the minimum inhibitory concentrations (MICs) of MMC and antibiotics against clinical Aeromonas isolates using broth microdilution. Synergistic effects of MMC with antibiotics were determined via time-kill studies. MMC's intracellular killing effects were analyzed using a representative Aeromonas isolate. Efficacy of combined therapies was assessed in a neutropenic mouse model. MMC-induced SOS response was evaluated using cell elongation method, and RNA extraction and quantitative real-time PCR.

Results: Combining 1/8⨯ MIC of mitomycin C (MMC) with either 1⨯ or 1/2⨯ MIC of LVX demonstrated significant synergistic effects over 24 h in vitro. In a neutropenic mouse model, the combination of MMC (2 mg/kg or 1 mg/kg) with LVX achieved survival rates of 100 % and 80 %, respectively, compared to 0 % survival with monotherapy. MMC induced marked cell elongation and division inhibition in response to escalating doses. However, the combination therapy's enhancement did not surpass the effects of individual drug treatments. Notably, combination therapy reduced recA activator levels below those observed with either drug alone, suggesting rapid bacterial cell death curtailed further expression of recA and lexA. Alternatively, extensive DNA damage may have overwhelmed bacterial DNA repair mechanisms, rendering them ineffective.

Conclusions: These findings suggest that MMC may serve as a potential antimicrobial agent, particularly when used in combination with antibiotics. The integration of MMC with antibiotic therapy offers a promising approach for the treatment of Aeromonas infections and holds potential for future clinical applications.

Background: Urinary tract infections (UTIs) are prevalent bacterial infection, with uropathogenic Escherichia coli (UPEC) as the primary causative agent. The outer membrane of UPEC contains a lipopolysaccharide (LPS), which plays crucial roles in the host's immune response to infection. Neutrophils use neutrophil extracellular traps (NETs) are mechanism by which neutrophils defend against bacterial infections. However, the exact mechanism by which a bacterial LPS induces NET formation is not well understood. Therefore, the objective of this study is to identify the possible mechanism of LPS-mediated NETs and dissect the LPS domains of UPEC that predominantly modulate NET formation and NET-mediated killing.

Methods: To investigate the mechanism of bacterial LPS-induced NET formation, we constructed UPEC CFT073 mutants that had rfaD, rfaL and the wzzE deleted with individual LPS biosynthetic genes including the inner core synthase, O-antigen ligase and O-antigen polymerase, respectively. Subsequently, we evaluated the NET/reactive oxygen species (ROS)/IL-1β induction abilities and assessed the activation of toll-like receptor 4 (TLR4)/JNK signaling by CFT073 and its mutants.

Results: The results showed that the O-antigen of CFT073 LPS is essential for inducing NET formation through TLR4/JNK/NOX pathways. Inhibition of either pathway significantly decreased the production of ROS, induction of NETs, and secretion of IL-1β.

Conclusion: Our results demonstrate that CFT073 LPS is essential for inducing ROS-dependent NETs and IL-1β secretion from neutrophils. This study also provides evidence for the crucial roles of O-antigen in the immune response to UPEC infection, as well as its potential as a therapeutic target for the treatment of UTIs.

Background/purpose: Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen with a negative economic impact on the global swine industry. In 2019, a suspected highly pathogenic strain, NPUST-108-929/2019 (108-929), was isolated from a pig farm in Pingtung with an outbreak of high mortality and analyzed. The characteristics of PRRSV 108-929 have barely been studied.

Methods: This study was to evaluate pathogenicity through animal challenge experiments using PRRSV 108-929 and antigenic characterization of this novel PRRSV.

Results: This PRRSV strain is PRRSV 2, belonging to lineage 3 based on open reading frame 5 sequence analysis. Four putative N-linked glycosylation sites (N32, N35, N44 and N51) are located on glycoprotein 5. Experimental results revealed that high fever occurred at 3 days postinoculation (dpi) in the high-titer inoculation (HIN) group (2 × 10⁴ TCID₅₀/mL), 8 dpi in the high-titer contact (HC) group, 4 dpi in the low-titer inoculation (LIN) group (2 × 10³ TCID₅₀/mL) and 9 dpi in the low-titer contact (LC) group. All pigs in each PRRSV 108-929 challenge and contact group showed severe clinical signs, such as high fever (>40.5 °C) and significant weight loss. Deaths occurred only in the HIN group; the survival rate was 60 %. All the piglets except the control group piglets showed high viremia titers (6.04-8.28 log¹⁰ copies/μL).

Conclusion: The pathogenic characteristics of PRRSV 108-929 suggest that it is a highly virulent PRRSV strain at both the farm and laboratory levels.

Background: Previously we identified a complex of non-structural protein (NS) 1 - Thrombin (NST) in dengue infected patients. Here, we investigated how the concentration of NS1 and NST differ in various dengue severity levels as well as their demographic and clinical features. Several comorbid (hypertension, diabetes, and chronic renal failure) often found in dengue patients were also measured and analyzed.

Methods: A total of 86 dengue patients (52 not severe and 34 severe), were enrolled and had their blood taken. Blood samples were further verified for clinical blood parameters, including liver and renal function tests and serologic assays (NS1 and NST). Patients' severity was grouped based on WHO 2009 classification, which separates patients into dengue without warning signs (DNWS), dengue with warning signs (DWWS), and severe dengue (SD). DWWS is explained as DNWS with warning signs (persistent abdominal pain, persistent vomiting, liver enlargement, bleeding (any kind), fatigue, and restlessness). SD are those with severe plasma leakage, severe bleeding, or severe organ impairment. Multivariate regression analysis was used to predict the role of NST on the dengue severity development and receiver operating characteristic (AUROC) test was utilized to evaluate separability.

Results: The analysis revealed that NS1 significantly impacts the disease outcome (p 0.018, OR = 2.467 (1.171-5.197)) but not beyond the effect through NST (p 0.108, OR = 0.085 (0.004-1.719)). We also prove that NST was a better severity biomarker compared to NS1, as it can predict progression from DNWS to DWWS (AUC: NS1 = 0.771∗∗, NST = 0.81∗∗) and SD (AUC: NS1 = 0.607, NST = 0.754∗) significantly.

Conclusions: This finding suggests the importance of NST in mediating the NS1 effect to promote dengue severity progression and its promising capability as an acute stage dengue severity biomarker.