Future microbiology最新文献

Aims: Anti-tumor vaccines that target the early proteins E6 and E7 of human papillomavirus (HPV) type 16 represent a potential immunotherapy for cervical cancer, although underlying mechanisms remain unclear. Lactococcus lactis (L.L) is generally regarded as safe (GRAS) which has potential as vehicle. Study investigated the immunoregulatory effect of L.L on dendritic cells (DCs) activation. Besides, antigen delivery and anti-tumor effects of DC-based vaccine prepared with recombinant L.L vaccine (L.L-De) carrying prokaryotic-eukaryotic HPV-16 E6E7 fusion antigen were explored.

Methods: Study performed flow cytometry and MTT to analyze the adjuvant efficacy in promoting DC activation and proliferative capacity of T lymphocytes. The anti-tumor effect of DC vaccine prepared with L.L-De was assessed in C57BL6 tumor model.

Results: Recombinant L.L carrying the expression frame for HPV-16 E6E7 fusion protein in prokaryotic-eukaryotic expression systems exhibited antigen-promoting and cross-presenting adjuvant activity successfully. the developed DC-L.L-De vaccine induced antigen-specific Th-1 and cytotoxic T lymphocyte responses, which inhibited TC-1 tumor growth.

Conclusions: This study demonstrated that recombinant L.L which carries a dual-expression antigen frame, is a promising vector for tumor antigen delivery.

Fluconazole resistance in Candida parapsilosis is an increasing global concern, with resistance rates varying widely and reaching up to 80% in some regions. This trend has led to hospital outbreaks, primarily driven by mutations in the ERG11 gene, especially the Y132F substitution. The clinical relevance of fluconazole resistance remains controversial, as studies have yielded conflicting results regarding its impact on mortality. While some studies described an increased mortality associated with resistant strains, others reported no significant difference. Treatment options are limited: echinocandins and liposomal amphotericin B (L-AmB) are commonly used alternatives, but their use is challenged by intrinsic and emerging echinocandin resistance and L-AmB toxicity and cost. These limitations emphasize the need for robust antifungal stewardship and the development of new therapies. Novel agents such as rezafungin, fosmanogepix, and ibrexafungerp have shown promising activity against fluconazole-resistant C. parapsilosis, though further clinical studies are needed to confirm their efficacy. This narrative review aims to summarize current evidence on the epidemiology, clinical implications, and therapeutic approaches for fluconazole-resistant C. parapsilosis infections.

Aim: In this study, we evaluated the antifungal potential of halogenated and nitro thiosemicarbazones and phenoxy-hydrazone-thiazole derivatives against Sporothrix clinical strains.

Methods: Antifungal activity of 10 compounds was assessed by broth microdilution. Cytotoxicity of the compounds was determined. Structure-activity relationship studies were performed.

Results: 2-(3-(3-Bromophenoxi)-2-butanilideno)thiosemicarbazone (named DT 06) and 2-(3-(4-Nitrophenoxi)-2-butanilideno)thiosemicarbazone (named DT 24) showed antifungal activity with MICs from 16 to 128 μg.mL^-1. All compounds showed low toxicity on splenocytes and macrophages cell lines.

Conclusion: Molecular hybrids of halogenated and nitro thiosemicarbazones and phenoxyhydrazone-thiazoles have proved to be promising compounds with low toxicity against Sporothrix clinical isolates, especially derivatives containing the thiosemicarbazone class. Furthermore, this study identified the first Sporothrix mexicana related to human sporotrichosis in Brazil. It is noteworthy that this environmental isolate was transmitted to the patient by zoonotic route.

Helicobacter pylori infects more than half of the world's population. Chronic H. pylori infection is associated with the development of precancerous gastric conditions, including chronic atrophic gastritis and intestinal metaplasia, which may progress to peptic ulcer disease and gastric cancer. In 2020, an estimated 1.09 million new cases of gastric cancer were reported worldwide. Gastric cancer continues to pose a significant health burden and is the fourth leading cause of cancer-related deaths globally, with an estimated 769,000 deaths occurring annually. To decrease gastric cancer-related deaths, international guidelines recommend H. pylori eradication in all infected individuals. Increasing antibiotic resistance of H. pylori has significantly compromised the effectiveness of standard eradication regimens, highlighting the urgent need for alternative and effective treatment strategies. Over the past decade, molecular technologies and genome sequencing have advanced H. pylori diagnosis and treatment. This comprehensive review discusses the latest evidence on H. pylori management to guide the development of effective testing and treatment strategies. It also offers updates for clinicians, including the optimized H. pylori diagnosis, the history of H. pylori treatment and guideline development, updated empirical H. pylori treatment regimens, molecular testing for tailored H. pylori eradication, and next-generation sequencing of the gastric microbiome.

Aim: We evaluated the in vitro activity of isavuconazole against different Candida clinical species from Brazil, with an emphasis on C. auris, using CLSI and EUCAST, and compared the results to expand the literature on this new triazole.

Methods: A total of 102 strains of Candida spp. were isolated from critically ill patients admitted to tertiary hospitals in Recife, Pernambuco, Brazil. All isolates were identified using MALDI-TOF MS and tested using broth microdilutions.

Results: The species identified were C. auris (62), C. albicans (14), C. tropicalis (9), C. parapsilosis (5), C. glabrata (3), C. metapsilosis, C. orthopsilosis (2) each, C. duobushaemulonii, Meyerozyma guilliermondii, Clavispora lusitaniae, C. nivariensis, and Wickerhamomyces anomolus (1). A modal MIC₉₀ of ≤0.008 µg/mL and a wild-type modal upper limit value of <0.03 µg/mL were found. Thus, 99.1% (CLSI) and 95.1% (EUCAST) of the strains were wild-type. The overall essential agreement rate between the methods was 95.1% (±2 log² dilutions) and 89.2% (±1 log² dilution).

Conclusion: Both methodologies were useful for evaluating the antifungal potential of isavuconazole and highlighted the low MICs of this triazole against the Brazilian collection of Candida spp., especially the emerging yeast C. auris.

Aim: Urinary tract infections (UTIs) caused by Proteus mirabilis are common infectious diseases. Currently, no vaccine is available against UTIs, making the development of an effective vaccine a critical goal to reduce the prevalence and antibiotic resistance of UTIs. Hence, we have investigated the immunogenicity and protective potential of a bivalent vaccine candidate comprising the iron scavenger receptors PMI1426 and PMI1945 from P. mirabilis in mice.

Methods: In this study, vaccine candidates composed of PMI1426 and PMI1945 from P. mirabilis were developed, and their immunogenicity, efficacy, and synergistic effects were evaluated in mice.

Results: Serum levels of IgG, IgG isotypes, IgA, and urinary IgA, as well as cytokine levels including IFN-γ, IL-4, and IL-17 were significantly elevated following vaccination with PMI1426 and PMI1945 as compared to the controls. The addition of alum enhanced the immune responses in both single and combined vaccine formulations. Furthermore, bacterial colonization in the bladder of mice challenged with P. mirabilis was significantly reduced in mice received the proteins admixed with alum compared to control groups.

Conclusion: Our results support the development of a promising vaccine candidate against P. mirabilis UTIs. Future human clinical trials are needed to validate the efficacy and safety of the vaccine candidates.

Staphylococcus aureus is a pathogen associated with various diseases, exhibiting biofilm ability and antimicrobial resistance. The search for new antimicrobial agents, especially natural ones, is crucial. This study evaluated the antibacterial and antibiofilm activities of the aqueous leaf extract from Eugenia dysenterica against S. aureus. Healthy leaves were dried, powdered and infused in water to obtain the extract. Reference strains S. aureus ATCC 25,923 and ATCC 29,213 were employed as model organisms. The minimum inhibitory concentration (MIC) was assessed using the microdilution technique in 96-well polystyrene microplates. The minimum bactericidal concentration (MBC) was evaluated by plating on standard count agar. Test surface assays were performed with polystyrene coupons, where the count of viable sessile cells (CVSC) was determined after sonication and agitation. Biofilm resistance was assessed after exposure to a chlorinated compound. The extract showed antimicrobial activity, with MICs values of 156-313 μg/mL and MBC values of 625-1,250 μg/mL. Antibiofilm activity was observed at inhibitory and subinhibitory concentrations. Even when CVSC was similar, the extract increased biofilm sensitivity to chlorinated compounds. The antimicrobial and antibiofilm potential of the aqueous leaf extract of E. dysenterica could aid S. aureus control in various fields, including the food and medical industries.