Failure in the treatment of P. aeruginosa, due to its broad spectrum of resistance, has been associated with increased patient mortality. One alternative approach for infection control is quorum quenching which was found to decrease virulence of such pathogen. In this study, the efficiency of a recombinant Ahl-1 lactonase formulated as a hydrogel was investigated to control the infection of multidrug resistant (MDR) P. aeruginosa infected burn using a murine model. The recombinant N-acylhomoserine lactonase (Ahl-1) was formulated as a hydrogel. To test its ability to control the infection of MDR P. aeruginosa, a thermal injury model was used. Survival rate, and systemic spread of the infection were evaluated. Histopathological examination of the animal dorsal skin was also done for monitoring the healing and cellular changes at the site of infection. Survival rate in the treated group was 100% relative to 40% in the control group. A decrease of up to 3 logs of bacterial count in the blood samples of the treated animals relative to the control group and a decrease of up to 4 logs and 2.3 logs of bacteria in lung and liver samples, respectively were observed. Histopathological examination revealed more enhanced healing process in the treated group. Accordingly, by promoting healing of infected MDR P. aeruginosa burn and by reducing systemic spread of the infection as well as decreasing mortality rate, Ahl-1 hydrogel application is a promising strategy that can be used to combat and control P. aeruginosa burn infections.
Amid the COVID-19 outbreak, several bioinformatic analyses have been conducted on SARS-CoV-2 virus genome. Numerous studies rushed to fill the gap about this novel virus. Comparison with other related sequences, structural predictions of the produced proteins, determination of variations in amino acid residues and depiction of possible drug and vaccine targets have been the focus of scientific research from the beginning of this year. In addition to discussing the viral taxonomy, clinical features, life cycle, and genome organization, this review will focus on the recent updates in genome and viral proteins characterization and potential therapeutic and vaccine candidates developed so far. Comparative studies with related genomes and proteins provide understanding for the viral molecular mechanisms and suggest targets for therapeutics and vaccinology trials to stop the escalation of this new virus. This pandemic, with its resulting social and economic afflictions, will definitely have significant marks on our lives in the following years.
Acyl homoserine lactones (AHLs) are the most common class of quorum sensing signal molecules (autoinducers) that have been reported to be essential for virulence of many relevant pathogenic bacteria such as Pseudomonas aeruginosa. New approach for controlling infections of such bacteria is through quorum quenching. In this study, the acyl homoserine lactone inhibitory activity of the crude enzyme from a Bacillus weihenstephanensis-isolate P65 was characterized. The crude enzyme was found to have relatively high thermal stability and was stable in pH range 6 to 9. The crude enzyme extract was found to have lactonase activity of 36.3 U/mg total protein. Maximum enzyme activity was achieved within a range of 28–50°C and pH 6–9. None of the metals used enhanced the activity neither did EDTA inhibit it. However, a concentration of 10 mM Fe+2 reduced the activity to 73.8%. Catalytic activity and kinetic constants were determined using hexanoyl homoserine lactone as a substrate. Studying enzyme substrate specificity using synthetic standard signals displayed broad spectrum of activity. The enzyme was found to be constitutive. Isolation and complete nucleotide sequence of the respective lactonase gene were done and submitted to the Genbank database under accession code KC823046.
The understanding of any disease calls for studying specific biological structures called epitopes. One important tool recently drawing attention and proving efficiency in both diagnosis and vaccine development is epitope mapping. Several techniques have been developed with the urge to provide precise epitope mapping for use in designing sensitive diagnostic tools and developing rpitope-based vaccines (EBVs) as well as therapeutics. In this review, we will discuss the state of the art in epitope mapping with a special emphasis on accomplishments and opportunities in combating COVID-19. These comprise SARS-CoV-2 variant analysis versus the currently available immune-based diagnostic tools and vaccines, immunological profile-based patient stratification, and finally, exploring novel epitope targets for potential prophylactic, therapeutic or diagnostic agents for COVID-19.
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