Development of innovative multi-epitope mRNA vaccine against Pseudomonas aeruginosa using in silico approaches.

The rising issue of antibiotic resistance has made treating Pseudomonas aeruginosa infections increasingly challenging. Therefore, vaccines have emerged as a viable alternative to antibiotics for preventing P. aeruginosa infections in susceptible individuals. With its superior accuracy, high efficiency in stimulating cellular and humoral immune responses, and low cost, mRNA vaccine technology is quickly replacing traditional methods. This study aimed to design a novel mRNA vaccine by using in silico approaches against P. aeruginosa. The research team identified five surface and antigenic proteins and selected their appropriate epitopes with immunoinformatic tools. These epitopes were then examined for toxicity, allergenicity and homology. The researchers also checked their presentation and identification by major histocompatibility complex cells and other immune cells through valuable tools like molecular docking. They subsequently modeled a multi-epitope protein and optimized it. The mRNA was analyzed in terms of structure and stability, after which the immune system's response against the new vaccine was simulated. The results indicated that the designed mRNA construct could be an effective and promising vaccine that requires laboratory and clinical trials.

Molecular characterization of Staphylococcus aureus isolated from hospital-acquired infections in Ilam, Iran.

OBJECTIVE: This research study was undertaken to investigate antimicrobial resistance patterns and the prevalence of hospital-acquired infections (HAIs). The study focuses on common microorganisms responsible for HAIs and explores emerging challenges posed by antimicrobial drug-resistant isolates. METHODS: A comprehensive analysis of 123 patients with HAIs, hospitalized in surgical department and intensive care unit (ICU) at Imam Khomeini Hospital, Ilam, Iran, was conducted over a six-month period. Pathogenic bacterial isolates, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA), were isolated and subjected to antibiotic susceptibility testing. RESULTS: The study findings revealed a significant prevalence of multidrug-resistant (MDR) isolates, of which 73.3% were MRSA. Notably, 6.7% of S. aureus isolates exhibited resistance to vancomycin, indicating the emergence of VRSA. Respiratory infections were identified as the most prevalent HAI, constituting 34.67% of cases, often arising from extended ICU stays and invasive surgical procedures. Furthermore, patients aged 60 and above, particularly those associated with MDR, exhibited higher vulnerability to HAI. CONCLUSIONS: This research sheds light on the intricate interplay between drug resistance and HAI, highlighting the imperative role of rational antibiotic use and infection control in addressing this critical healthcare challenge.

Clinical symptoms, pathogenesis and postoperative course of non-specific constrictive pericarditis with dumbbell-shaped heart.

Non-specific chronic constrictive pericarditis is a rare and debilitating chronic infection in developed countries and its rapid diagnosis and treatment has not affected its outcome and complication. A 15-year-old male, well nourished, negative HIV test, and without a history of previous pulmonary tuberculosis, was admitted to our hospital for exertional dyspnea (New York Heart Association, NYHA, functional class II). Our patient had had no pulmonary tuberculosis during childhood, had received anti-tuberculosis treatment, and was referred to our center for further surgical pericardiectomy.

Antimicrobial combination effects against multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa strains: A cross-sectional study.

Background and Aims: Emergence of multidrug resistance in non-fermenting Gram-negative bacilli is a threat to public health. Combination therapy is a strategy for the treatment of antibiotic-resistant infections. Methods: In this cross-sectional study, a total of 63 nonduplicate clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa were collected from various specimens. Identification of bacterial isolates was performed by phenotypic and molecular tests. Antibiotic susceptibility patterns and detection of ß-lactamase genes were determined using the broth microdilution and polymerase chain reaction (PCR) techniques, respectively. Then, the combined effects analysis was determined by the checkerboard method. Based on the status of resistance to carbapenems (imipenem and meropenem), 25 isolates of each genus were selected for further investigation. Results: For A. baumannii, bla OXA-23, bla OXA-58, and bla OXA-48 genes were positive in 21 (84%), 17 (68%), and 11 (44%) of isolates, respectively. In P. aeruginosa isolates, bla VIM was the most common gene (44%) and other genes including bla IMP, bla NDM, and bla OXA-23 were found in nine (36%), six (24%), and three (12%) isolates, respectively. Meropenem (MER)-tigecycline (TIG) had a significant synergistic effect against 20 (80%) A. baumannii (p value < 0.001). This combination was also efficient against 5 (20%) P. aeruginosa isolates. Moreover, the other combination, tigecycline-amikacin (TIG-AMK) was effective against 10 (40%) A. baumannii isolates. The combination of colistin (COL) and MER showed a significant synergistic effect against 21 (84%) A. baumannii (p value < 0.001) and 17 (68%) P. aeruginosa isolates (p value < 0.001). Conclusion: The MER-TIG and COL-MER combinations are promising options against resistant bacteria. Our study could be helpful for the development of a new treatment recommendation.

Effects of non-tuberculous mycobacteria on BCG vaccine efficacy: A narrative review.

The Mycobacterium tuberculosis bacterial pathogen is responsible for the ongoing global tuberculosis (TB) epidemic. Bacille Calmette-Guérin (BCG), the only currently approved TB vaccine, is successful in preventing disseminated disease in newborns. However, it has a variable efficacy against pulmonary TB in adults. This protective effect of the vaccine varies greatly among different populations and geographical areas, which the increased exposure of particular populations to non-tuberculous mycobacteria (NTM) is considered as one of the reasons for this issue. Numerous studies have shown that exposure to NTM species causes the host immune system to be improperly primed. It has also been suggested that NTM species may be blamed for reduction in BCG vaccine effectiveness against M. tuberculosis. The increased exposure of certain populations to NTM has diverse effects on BCG efficacy. Moreover, the exposure to NTM can induce opposite effects on BCG efficacy depending on the NTM exposure route and survivability. A detailed understanding of the impact of NTM exposure on the efficacy of the BCG vaccine is essential for ongoing efforts to develop new TB vaccines as it may ultimately be a crucial success factor. The aim of this study was to review the findings of the studies focusing on the effects of NTM on BCG vaccine efficacy in animal models.

Antibacterial and Immunoregulatory Effects of Metformin against Helicobacter pylori Infection in Rat Model.

Introduction: Helicobacter pylori (H. pylori) induces gastritis by stimulating Th17 cells and related cytokines. The aim of our study was to investigate the synergistic effect of metformin with amoxicillin as an antibiotic in inhibiting H. pylori and modulating the immune response in a rat model. Methods: Forty-five male Sprague-Dawley rats were divided into seven groups and infected with H. pylori. Over the course of 14 days, all animals were treated with metformin and amoxicillin alone and in combination. The antibacterial activity of metformin was evaluated by growth curves and colony counts. The immunoregulatory effect on Treg/Th17 balance was assessed by flow cytometry, and the cytokine profile of IL-17A, IL-1ß, IL-6, IL-8, TGF-ß, and IL-10 was determined by ELISA. The effect of metformin on gene expression of cagA and IL-8 was investigated by RT-PCR. Pathological changes were assessed by hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining. Results: Metformin showed weak antibacterial activity against clinically isolated H. pylori. However, the combination of metformin and amoxicillin (AMX) showed strong synergistic antibacterial activity (ΣFIC = 0.24). Compared with AMX, metformin reduced inflammation and tissue damage but resulted in increased bacterial growth. During metformin administration, both TGF-ß levels and Treg cells increased dramatically (P = 0.002). In synergy with AMX, metformin decreased the effective dose of antibiotic to eradicate H. pylori. Conclusions: The combination of metformin with potential antibiotics such as AMX had a positive effect on the relief of H. pylori-related inflammation by inducing Treg cells while successfully eliminating H. pylori.