Antibody therapy against antibiotic-resistant diarrheagenic Escherichia coli: a systematic review.

Over four billion episodes of diarrhea occur annually in developing countries with diarrheagenic Escherichia coli (DEC) outbreaks also being reported, until now bacterial diarrhea is conventionally addressed by the antibiotic treatment regimes. In recent decades, the emergence of antimicrobial-resistant strains has become a major obstacle in diarrheal treatment; hence, novel and ideal therapeutics are needed. Notably, 80% of DEC is resistant to first-class antibiotics. Among the existing strategies, passive immunization is considered as an alternative to combat drug-resistant bacteria. Antibodies specific to an antigen can be used for prophylactic and therapeutic purposes. In this review, we have systematically discussed the effect of passive immunotherapy to combat DEC and explored the types and advancements in antibodies used against antibiotic-resistant DEC.

Targeting AgrA quorum sensing regulator by bumetanide attenuates virulence in Staphylococcus aureus - A drug repurposing approach.

AIMS: The present study aims to target the quorum sensing (QS) accessory gene regulator A (AgrA) of Staphylococcus aureus to curtail bacterial virulence through drug repurposing approach. MAIN METHODS: In silico screening of chemical ligands that bind specifically to the S. aureus C-LytTR domain of AgrA (AgrAC) was carried out. AgrA inhibition and downregulation of virulence genes linked to QS system of S. aureus were determined. Efficacy, dermal toxicity and drug tolerance induction were tested in Balb/C mice dermonecrosis model. KEY FINDINGS: Bumetanide bound to the conserved amino acid Tyr-229 of AgrA and showed 70% AgrA inhibition at 0.1 µM. Highly significant reduction in the expression of representative virulence genes such as alpha-hemolysin (~5 log2-fold), phenol-soluble modulins (~4 log2-fold) and panton-valentine leukocidin (~3 log2-fold) was noted in vitro. In vivo studies signified bumetanide to be highly effective in controlling the ulcer development and promoted wound healing. Also, the tested substance did not have dermal toxicity and no tolerance induction as well. SIGNIFICANCE: Targeting the QS regulators could be a possible alternative approach to curtail virulence in S. aureus. In addition, if the QS inhibitors are repurposed it could accelerate the drug development process and reduce the cost. The identified drug bumetanide inhibited AgrA and the results were in comparable to that of a known virulence inhibitor, diflunisal. The newly reported results of bumetanide in this study are expected to mark the drug's visibility for antibiotic adjunctive therapy and topical drug formulations for skin infections research.

Role of tau protein in Alzheimer's disease: The prime pathological player.

Alzheimer's disease (AD) is a prevalently found tauopathy characterized by memory loss and cognitive insufficiency. AD is an age-related neurodegenerative disease with two major hallmarks which includes extracellular amyloid plaques made of amyloid-ß (Aß) and intracellular neurofibrillary tangles of hyperphosphorylated tau. With population aging worldwide, there is an indispensable need for treatment strategies that can potentially manage this developing dementia. Despite broad researches on targeting Aß in the past two decades, research findings on Aß targeted therapeutics failed to prove efficacy in the treatment of AD. Tau protein with its extensive pathological role in several neurodegenerative diseases can be considered as a promising target candidate for developing therapeutic interventions. The abnormal hyperphosphorylation of tau plays detrimental pathological functions which ultimately lead to neurodegeneration. This review will divulge the importance of tau in AD pathogenesis, the interplay of Aß and tau, the pathological functions of tau, and potential therapeutic strategies for an effective management of neuronal disorders.

Inflammation in myocardial injury- Stem cells as potential immunomodulators for myocardial regeneration and restoration.

The ineffective immunosuppressant's and targeted strategies to neutralize inflammatory mediators have worsened the scenario of heart failure and have opened many questions for debate. Stem cell therapy has proven to be a promising approach for treating heart following myocardial infarction (MI). Adult stem cells, induced pluripotent stem cells and embryonic stem cells are possible cell types and have successfully shown to regenerate damaged myocardial tissue in pre-clinical and clinical studies. Current implications of using mesenchymal stem cells (MSCs) owing to their immunomodulatory functions and paracrine effects could serve as an effective alternative treatment option for rejuvenating the heart post MI. The major setback associated with the use of MSCs is reduced cell retention, engraftment and decreased effectiveness. With a few reports on understanding the role of inflammation and its dual effects on the structure and function of heart, this review focuses on these missing insights and further exemplifies the role of MSCs as an alternative therapy in treating the pathological consequences in myocardial infarction (MI).

Characterization of microfouling and corrosive bacterial community of a firewater distribution system.

This investigation provides generic information on the culturable corrosive and the microfouling bacterial community in a firewater distribution system that uses freshwater. Conventional microbiological methods were used for the selective isolation of the major microfouling bacteria. The isolates were characterized by 16S rRNA gene sequencing and the biofilm as well as the corrosion characteristics of the isolates were evaluated. Pseudomonas aeruginosa and Bacillus cereus were predominantly observed in all the samples analysed. Denaturing gradient gel electrophoresis (DGGE) was carried out for the various samples of firewater system (FWS) and the high intensity bands were sequenced to identify the predominant bacteria. Bacterial groups such as Cyanobacteria, Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes were identified. Biofilm thickness was recorded using confocal scanning laser microscopy (CSLM). This was the first study to report Lysinibacillus fusiformis in a firewater system and its role in iron corrosion. Sulphidogenic bacteria Tissierella sp. and Clostridium bifermentans generated sulphides in the range of 400-900 ppm. Significant corrosion rates of carbon steel (CS) coupons were observed up to 4.3 mpy. C. bifermentans induced more localized corrosion in CS with a pit diameter of 50 µm. Overall, the data on the characterization of the fouling bacteria, their biofilm forming potential and subsequent metal deterioration studies supported in designing an effective water treatment program.