The development of thymol-isatin hybrids as broad-spectrum antibacterial agents with potent anti-MRSA activity.

Bacterial resistance toward available therapeutic agents has become a nightmare for the healthcare system, causing significant mortality as well as prolonged hospitalization, thereby needing the urgent attention of research groups working on antimicrobial drug development worldwide. Molecular hybridization is a well-established tool for developing multifunctional compounds to tackle drug resistance. Inspired by the antibacterial profiles of isatin and thymol, along with the efficiency of a triazole linker in molecular hybridization, herein, we report the design, synthesis and antibacterial activity of a novel series of triazole tethered thymol-isatin hybrids. Most of the hybrids exhibited a broad-spectrum antibacterial efficacy against standard human pathogenic as well as clinically isolated multidrug-resistant bacterial strains listed in the WHO's 'priority pathogen' list and also in the ESKAPE group. Among them, hybrid compound AS8 was the most effective against methicillin-resistant Staphylococcus aureus (MIC = 1.9 µM and MBC = 3.9 µM), exhibiting biofilm inhibitory potential. AS8 exhibited dehydrosqualene synthase (CrtM) inhibitory potential in MRSA and decreased the production of virulence factor staphyloxanthin, which is one of the key mechanisms of its anti-MRSA efficacy, which was further supported by molecular docking and simulation studies. Moreover, AS8 was found to be non-toxic and showed a potent in vivo antibacterial efficacy (90% survival at 10 mg kg-1) as well as a modulated immune response in the larva-based (Galleria mellonella) model of systemic infections. Overall findings confirmed that AS8 can be a promising candidate or take the lead in the treatment and further drug development against drug-resistant infectious diseases, especially against MRSA infections.

In silico molecular modelling studies and antibiofilm efficacy of shikonin against Candida albicans: mechanistic insight.

In the recent past, the occurrence of fungal infections has increased drastically and candidiasis, caused prominently by Candida albicans, is foremost among them which has caused significant mortality and morbidity majorly in immune-compromised patients. Shikonin is a well-known natural naphthazarin derivative with promising antifungal efficacy, but it's mechanism of action is still unclear. Keeping this in view, present work was designed to get a mechanistic insight of anti-candida efficacy of shikonin via in vitro experiments and in situ molecular modelling studies. The current exploratory study is based on research that uses both qualitative and quantitative techniques, including minimum inhibitory concentration, minimum biofilm inhibitory concentration, time kill assay, cell cycle analysis and apoptotic assays, static biofilm formation assays, microscopic biofilm assessment assays, ergosterol content estimation and molecular docking/simulation studies. The study revealed a notable effect of shikonin against Candida albicans, including retardation of biofilms. Shikonin, with its increasing concentration leads to candidal cell apoptosis and necrosis establishing its dose-dependent effect. Additionally, it exhibited fungicidal activity via a mechanism of action likely related to ergosterol complexation which was further corroborated by molecular docking and simulation studies.

Microplastic Pollution: An Emerging Threat to Terrestrial Plants and Insights into Its Remediation Strategies.

Microplastics (MPs) are ubiquitous and constitute a global hazard to the environment because of their robustness, resilience, and long-term presence in the ecosystem. For now, the majority of research has primarily focused on marine and freshwater ecosystems, with just a small amount of attention towards the terrestrial ecosystems. Although terrestrial ecosystems are recognized as the origins and routes for MPs to reach the sea, there is a paucity of knowledge about these ecological compartments, which is necessary for conducting effective ecological risk assessments. Moreover, because of their high persistence and widespread usage in agriculture, agribusiness, and allied sectors, the presence of MPs in arable soils is undoubtedly an undeniable and severe concern. Consequently, in the recent decade, the potential risk of MPs in food production, as well as their impact on plant growth and development, has received a great deal of interest. Thus, a thorough understanding of the fate and risks MPs, as well as prospective removal procedures for safe and viable agricultural operations in real-world circumstances, are urgently needed. Therefore, the current review is proposed to highlight the potential sources and interactions of MPs with agroecosystems and plants, along with their remediation strategies.

Symptoms, risk factors, diagnosis and treatment of urinary tract infections.

Urinary tract infection (UTI) is a common microbial infection found in all ages and sexes which involves inflammation of the urinary tract. These infections can range from simple bladder inflammation, that is, cystitis, to severe cases of uroseptic shock. UTI ranks as the number 1 infection that leads to a prescription of antibiotics after a doctor's visit. These infections are sometimes distressing and even life threatening, and both males (12%) and females (40%) have at least one symptomatic UTI throughout their lives. Diagnostic failures in case of bacterial infections are the main contributing factor in improper use of antibiotics, delay in treatment and low survival rate in septic conditions. So, early diagnosis and appropriate therapy with antibiotics are the most significant requirements for preventing complicated UTI conditions such as urosepsis. This review article summarises the symptoms of the UTIs and the associated risk factors to it. The various conventional and recent diagnostic methods were also discussed in this review, along with treatment therapies with or without antibiotics.

Molecular characterization and antimicrobial susceptibility of bacterial isolates present in tap water of public toilets.

BACKGROUND: The present study was carried out to investigate the tap water quality of public toilets in Amritsar, Punjab, India. METHODS: Water samples from the taps of the public toilets were collected in sterile containers and physicochemical and bacteriological analysis was performed using standard methods. Also, genotypic and phenotypic characterization of the bacterial isolates was performed using different biochemical tests and 16S ribosomal RNA analysis. An antibiotic susceptibility test was performed using antibiotics based on their mode of action. A biofilm assay was performed to assess the adhesion potential of the isolates. RESULTS: A total of 25 bacterial isolates were identified from the water samples, including Acinetobacter junii, Acinetobacter pittii, Acinetobacter haemolyticus, Bacillus pumilus, Bacillus megaterium, Bacillus marisflavi, Bacillus flexus, Bacillus oceanisediminis, Pseudomonas otitidis, Pseudomonas sp. RR013, Pseudomonas sp. RR021, Pseudomonas sp. RR022, Escherichia coli and Enterobacter cloacae. The results of the antimicrobial susceptibility test revealed that the antibiotics cefodroxil, aztreonam, nitrofurantoin, cefepime, ceftazidime and amoxyclav were found to be mostly ineffective against various isolates. The biofilm assay revealed the weak, moderate and strong biofilm producers among them. CONCLUSIONS: The tap water in the public toilets was microbially contaminated and needs to be monitored carefully. The antibiotic susceptibility profile showed that of 25 bacterial isolates, 5 were multidrug resistant. Bacterial isolates exhibited strong to weak adhesion potential in the biofilm assay.

Menstrual Hygiene, Management, and Waste Disposal: Practices and Challenges Faced by Girls/Women of Developing Countries.

Menstruation and menstrual practices still face many social, cultural, and religious restrictions which are a big barrier in the path of menstrual hygiene management. In many parts of the country especially in rural areas girls are not prepared and aware about menstruation so they face many difficulties and challenges at home, schools, and work places. While reviewing literature, we found that little, inaccurate, or incomplete knowledge about menstruation is a great hindrance in the path of personal and menstrual hygiene management. Girls and women have very less or no knowledge about reproductive tract infections caused due to ignorance of personal hygiene during menstruation time. In rural areas, women do not have access to sanitary products or they know very little about the types and method of using them or are unable to afford such products due to high cost. So, they mostly rely on reusable cloth pads which they wash and use again. Needs and requirements of the adolescent girls and women are ignored despite the fact that there are major developments in the area of water and sanitation. Women manage menstruation differently when they are at home or outside; at homes, they dispose of menstrual products in domestic wastes and in public toilets and they flush them in the toilets without knowing the consequences of choking. So, there should be a need to educate and make them aware about the environmental pollution and health hazards associated with them. Implementation of modern techniques like incineration can help to reduce the waste. Also, awareness should be created to emphasize the use of reusable sanitary products or the natural sanitary products made from materials like banana fibre, bamboo fibre, sea sponges, water hyacinth, and so on.