Infectious disorders drug targets最新文献

Background: The understanding of the antibiotic resistance status of environmental nonO1/nonO139 V. cholerae (NOVC) in relation to other illnesses, which can vary in severity from mild to life-threatening, is limited. However, it is important to note that NOVC-related infections are increasing and serve as a significant illustration of emerging human diseases associated with climate change. The primary objective of the present study was to assess the rates of resistance observed in environmental NOVC isolates across various years, and regions, and their resistance rates.

Methods: We performed a systematic search of Scopus, PubMed, Web of Science, and EMBASE databases (until May 2024) following PRISMA guidelines. All statistical analyses were carried out using the statistical package R.

Results: Our analysis included a total of 34 studies. According to the meta-regression, chloramphenicol, rifampicin, ciprofloxacin, nalidixic acid, cotrimoxazole, kanamycin, trimethoprim, amoxicillin/clavulanic acid, and tetracycline resistance rate increased over time. The lowest resistance rates were observed in Austria (amoxicillin; 0.6%), the United States (kanamycin; 0.1% and tetracycline; 0.1%), Morocco (polymyxin B; 12%), and Spain (trimethoprim; 0.3%). Conversely, the highest resistance rates were found in Spain (amoxicillin; 61%), Indonesia (kanamycin and tetracycline; 94.9%), India (polymyxin B; 97.8%), and Morocco (trimethoprim; 48.9%).

Conclusion: The meta-analysis showed significant variability in antibiotic resistance patterns among environmental NOVC isolates across time and regions, emphasizing the need for targeted, time-specific, and country-specific approaches to address antibiotic resistance globally.

Introduction: Tuberculosis (TB) is a widespread infectious disease caused by Mycobacterium tuberculosis. It predominantly affects the lungs but can involve any organ in the body. Tracheo-oesophageal fistula (TEF) is one of the rare extrapulmonary manifestations of TB.

Case report: A 27-year-old male, otherwise healthy, reported to our outpatient department with complaints of fever, persistent cough, and significant weight loss. Subsequently, he was diagnosed with tuberculous tracheo-oesophageal fistula and pulmonary tuberculosis.

Discussion: The patient had an elevated ESR (52 mm) and underwent multiple imaging studies, including two normal barium swallow tests. Upper gastrointestinal endoscopy (UGIE) revealed two esophageal ulcers, one with a fistulous tract. Biopsy results suggested chronic esophagitis with granulomatous inflammation. Contrast-enhanced CT (CECT) of the thorax showed esophageal irregularities, air foci, and contrast extravasation into the bronchi, along with mediastinal lymphadenopathy and centrilobular nodules. Clinical and investigative findings suggested pulmonary tuberculosis with a tracheoesophageal fistula. The patient was discharged on a six-month antitubercular regimen with nutritional support via a nasogastric tube. Stent installation was planned if follow-up results were unfavorable.

Conclusion: Although tuberculosis is highly prevalent in India, TEF of tuberculous origin has been infrequently documented, particularly in young, healthy, immunocompetent individuals. The patient was successfully cured after initiating antitubercular therapy and subsequent follow-up.

Enteric fever is a multi-systemic illness of major public health concern. Also known as typhoid fever, it is caused due to both Salmonella typhi and Paratyphi species. Salmonella species have the ability to cause acute, latent, or chronic disease apart from biofilm formation. The outcome of infection depends on various factors, such as the growth state of Salmonella, the environmental conditions encountered at the time of infection, as well as the infected host, and the immune response elicited. If properly treated, many of the patients recover from the acute phase of enteric fever; however, only 3-5% of individuals can develop a chronic carrier state and can act as a reservoir of infection by continued shedding of bacteria in urine and faeces. In infected individuals, Salmonella colonizes the gall bladder and remains there long after symptoms subside, acting as a reservoir for the further spread of the disease. Symptomatic urinary tract infection (UTI) due to Salmonella is uncommon and is rarely encountered especially in an immunocompromised patient with some underlying abnormality involving the urinary tract. In this review, we have tried to explore new directions in the field of Salmonella causing UTI in immunocompetent patients, particularly as it relates to chronic infection.

Background: Clostridium difficile is an opportunistic infection that can lead to antibiotic- associated diarrhea and toxic megacolon.

Objective: This systematic review study aimed to investigate polyphenols' antibacterial and antitoxin properties and their effects on reducing complications related to C. difficile Infections (CDI).

Methods: This systematic review was conducted following the PRISMA guideline 2020. Multiple databases, including Web of Science, PubMed, Cochrane Library, EMBASE, and Scopus, were searched thoroughly for existing literature. After considering the inclusion and exclusion criteria for the review, 18 articles were included. Data were collected and registered into an Excel file for further investigations and conclusions.

Results: Polyphenols by reducing Reactive Oxygen Species (ROS) levels, increasing inflammatory factor Interleukin 10 (IL-10), reducing Nuclear Factor kappa B (NF-κB) and Tumour Necrosis Factor- α (TNF-α), IL-6, IL-1α, IL-1β, Granulocyte Colony-stimulating Factor (G-CSF), and Monocyte Chemoattractant Protein-1 (MCP-1) and Macrophage Inflammatory Protein-1 alpha (MIP-1α) levels, and regulating the expression of Bcl-2 and Bax, make the growth and replication conditions of C. difficile more difficult and prevent it from producing toxins. Furthermore, polyphenols can exhibit prebiotic properties, promoting the growth of beneficial Bifidobacterium and Lactobacillus species and consequently regulating gut microbiota, exerting antimicrobial activities against C. difficile. They also induce their beneficial effects by inhibiting the production of C. difficile TcdA and TcdB.

Conclusion: Polyphenols have been reported to inhibit C. difficile growth and toxin production by several mechanisms in preclinical studies. However, more clinical studies are needed to investigate their safety in humans.

Background: A biofilm refers to a community of microbial cells that adhere to surfaces that are surrounded by an extracellular polymeric substance. Bacteria employ various defence mechanisms, including biofilm formation, to enhance their survival and resistance against antibiotics.

Objective: The current study aims to investigate the resistance patterns of Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) in both biofilms and their planktonic forms.

Methods: E. coli and B. subtilis were used to compare resistance patterns in biofilms versus planktonic forms of bacteria. An antibiotic disc diffusion test was performed to check the resistance pattern of biofilm and planktonic bacteria against different antibiotics such as penicillin G, streptomycin, and ampicillin. Biofilm formation and its validation were done by using quantitative (microtiter plate assay) and qualitative analysis (Congo red agar media).

Results: A study of surface-association curves of E. coli and B. subtilis revealed that surface adhesion in biofilms was continuously constant as compared to their planktonic forms, thereby confirming the increased survival of bacteria in biofilms. Also, biofilms have shown high resistance towards the penicillin G, ampicillin and streptomycin as compared to their planktonic form.

Conclusion: It is safely inferred that E. coli and B. subtilis, in their biofilms, become increasingly resistant to penicillin G, ampicillin and streptomycin.

Background: Cuts and wounds are unfortunate yet inevitable events. Traditional remedies have historically harnessed various plants for wound healing, undergoing clinical and pre-clinical scrutiny. Hence, this systematic review focuses on clinically researched herbal formulations for wound healing.

Methodology: Following Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines, databases like Google Scholar, Web of Science, PubMed, Scopus, J-gate, and Ayush Research Portal were meticulously searched for clinical trials involving wound-targeting herbal formulations, alongside a comprehensive hunt for preclinical plant data.

Results: Among 623 screened documents, 26 published clinical trials spotlighting herbal wound healing formulations were identified. All studies showcased significant wound healing progress, with some surpassing standard betadine treatment. Only one study reported an adverse effect. Within the 26 formulations, 45 distinct plant species were employed, with 35 exhibiting wound healing attributes like antimicrobial, anti-inflammatory, and antioxidant activities scientifically. Enhanced collagen content, stabilized fibers, activated fibroblast cells, increased total protein, elevated growth factors, hydroxyproline, hexosamine, and tissue protein demonstrate the efficacy of plants, such as Hypericum perforatum, Centella asiatica, and Calendula officinalis in wound healing.

Conclusion: The findings of the current study indicated that medicinal plants are effective and safe agents for the treatment of wounds, though larger, well-designed trials are needed for definitive role confirmation.

Introduction: Spinal schwannomas are benign intradural extramedullary tumors of Schwann cells, while hemangiomas are common benign vascular tumors found in the vertebral column.

Case representation: This case study presents a 32-year-old male who developed both a spinal schwannoma and multiple thoracic vertebral haemangiomas following a COVID-19 infection and subsequent vaccination. The patient reported intermittent lumbar and thigh pain over 6-8 months. Magnetic resonance imaging (MRI) confirmed an intradural extramedullary schwannoma at the L5 vertebra and multiple thoracic haemangiomas at the T6-T7 levels. The schwannoma was surgically resected, and pathology confirmed the diagnosis. Postoperatively, the patient's symptoms improved significantly, with no complications.

Conclusion: This case raises questions about a possible link between COVID-19 and these spinal conditions. Further research is warranted to explore the potential association between viral infection, vaccination, and tumor development.

Aim: This study was undertaken to compare the proteomic profile of sequential isolates of Beijing lineage Mycobacterium tuberculosis (M. tuberculosis) from a patient who developed drugresistant tuberculosis (TB) in vivo during anti-tuberculosis therapy (ATT).

Introduction: Various studies have found the Beijing lineage of M. tuberculosis strongly associated with multidrug resistance (MDR) development.

Objectives: To identify and characterize the differentially expressed proteins during the in-vivo drug resistance conversion in M. tuberculosis Beijing lineage clinical isolates.

Methods: Drug-susceptible and drug-resistant M. tuberculosis isolates were confirmed as Beijing lineage. The isolates were grown in Middlebrook 7H9 medium for two weeks, and whole-cell lysate was prepared. Two-dimensional gel electrophoresis (2DGE) was used for proteomic analysis, and differentially expressed proteins were identified using MALDI-TOF-MS. Bioinformatics tools were used for molecular docking, phosphorylation, and pupylation site prediction.

Results: Seventeen proteins were found overexpressed in drug-resistant isolates as compared to drugsusceptible isolates, including the six proteins with unknown functions. Molecular docking showed that Isoniazid (INH) and Rifampicin (RIF) interacted with their conserved domains/active sites of these proteins.

Discussion: We characterized two paired clinical isolates from a patient, one being INH and RIF susceptible and other resistant. The comparative analysis of over expressed proteins showed that 5 of 17 proteins belonged to the cell wall and cell processes functional group, 3 to virulence, detoxification, adaptation functional group, and 3 to information pathways functional group, 2 proteins belonged to insertion sequences and phage functional group, and 1 each (Rv0242c, Rv2970c and Rv3208A) to lipid metabolism, intermediary metabolism & respiration and regulatory functional group. We found that the Rv1827, Rv2626c, Rv2714, Rv2970c, Rv3208A, and Rv3881c proteins showed significant interaction in-silico with INH and RIF.

Conclusions: These over-expressed proteins probably play an important role in drug resistance development, and further studies on drug resistance mechanisms could provide more details. We also believe that these over-expressed proteins could be used as biomarkers for early prediction of in-vivo drug-resistance development.

Multicellular surface-attached populations of bacteria embedded in the extracellular matrix are known as biofilms. Bacteria generally preferred to grow as biofilms. Quorum sensing (QS), detection of density of cell population through gene regulation, has been found to play an important role in the production of biofilms. Biofilm formation can increase the severity of infections that can lead to morbidity or mortality. Bacteria living within biofilms have a higher pattern of adaptive resistance to antibiotics. Antibiotic resistance is a barrier in the treatment of biofilmsinduced acute to chronic infections such as post-surgery infections, surgery-associated wound infections, endocarditis, joint infections, burn-related wound infections occurred, ventilator-associated pneumonia, etc. So it is urgent to discover or find out potent new drugs in fight against infectious diseases such as biofilms-associated infections. Medicinal plants or herbs are a rich source for fighting with biofilms-mediated infections. Phytochemicals have exhibited significant effects in the prevention of biofilms formation against different bacteria that are causing infections. Purified compounds such as berberine, tetrandrine, embelin, xanthorrhizol, bakuchiol, etc., exhibited promising biofilm inhibition actions against different pathogenic bacteria. Plant extracts that contain several phytochemicals are evaluated for its biofilm's inhibition property, and have shown significant potential in biofilm formation. Antibiofilm agents act by distinct mechanisms such as inhibiting the adherence of biofilms in a surface, preventing the biofilm formations, disrupting the matured biofilms, etc. This study is intended to reiterate about possibilities of plant extracts and purified compounds in the treatment of the prevention of bacterial biofilms-related infections.