Viral infections are a major threat to the human population due to the lack of selective therapeutic measures. The morbidity and mortality reported worldwide are very alarming against viral pathogens. The proinflammatory environment is required for viral inhibition by initiating the host immune response. The host immune response fights these pathogens by secreting different cytokines. Interleukin‐17 (IL‐17) a proinflammatory cytokine mainly produced by T helper type 17 cells, plays a vital role in the regulation of host immune response against various pathogens, including viruses. However, dysregulated production of IL‐17 induces chronic inflammation, autoimmune disorders, and may lead to cancer. Recent studies suggest that IL‐17 is not only involved in the antiviral immune response but also promotes virus‐mediated illnesses. In this review, we discuss the protective and pathogenic role of IL‐17 against various viral infections. A detailed understanding of IL‐17 during viral infections could contribute to improve therapeutic measures and enable the development of an efficient and safe IL‐17 based immunotherapy.
Bacterial binding to platelets is a key step in the development of infective endocarditis (IE). Sialic acid, a common terminal carbohydrate on host glycans, is the major receptor for streptococci on platelets. So far, all defined interactions between streptococci and sialic acid on platelets are mediated by serine-rich repeat proteins (SRRPs). However, we identified Streptococcus oralis subsp. oralis IE-isolates that bind sialic acid but lack SRRPs. In addition to binding sialic acid, some SRRP- isolates also bind the cryptic receptor β-1,4-linked galactose through a yet unknown mechanism. Using comparative genomics, we identified a novel sialic acid-binding adhesin, here named AsaA (associated with sialic acid adhesion A), present in IE-isolates lacking SRRPs. We demonstrated that S. oralis subsp. oralis AsaA is required for binding to platelets in a sialic acid-dependent manner. AsaA comprises a non-repeat region (NRR), consisting of a FIVAR/CBM and two Siglec-like and Unique domains, followed by 31 DUF1542 domains. When recombinantly expressed, Siglec-like and Unique domains competitively inhibited binding of S. oralis subsp. oralis and directly interacted with sialic acid on platelets. We further demonstrated that AsaA impacts the pathogenesis of S. oralis subsp. oralis in a rabbit model of IE. Additionally, we found AsaA orthologues in other IE-causing species and demonstrated that the NRR of AsaA from Gemella haemolysans blocked binding of S. oralis subsp. oralis, suggesting that AsaA contributes to the pathogenesis of multiple IE-causing species. Finally, our findings provide evidence that sialic acid is a key factor for bacterial-platelets interactions in a broader range of species than previously appreciated, highlighting its potential as a therapeutic target.
The magnitude and pace of global affliction caused by Coronavirus Disease-19 (COVID-19) is unprecedented in the recent past. From starting in a busy seafood market in the Chinese city of Wuhan, the virus has spread across the globe in less than a year, infecting over 76 million people and causing death of close to 1.7 million individuals worldwide. As no specific antiviral treatment is currently available, the major strategy in containing the pandemic is focused on early diagnosis and prompt isolation of the infected individuals. Several diagnostic modalities have emerged within a relatively short period, which can be broadly classified into molecular and immunological assays. While the former category is centered around real-time PCR, which is currently considered the gold standard of diagnosis, the latter aims to detect viral antigens or antibodies specific to the viral antigens and is yet to be recommended as a stand-alone diagnostic tool. This review aims to provide an update on the different diagnostic modalities that are currently being used in diagnostic laboratories across the world as well as the upcoming methods and challenges associated with each of them. In a rapidly evolving diagnostic landscape with several testing platforms going through various phases of development and/or regulatory clearance, it is prudent that the clinical community familiarizes itself with the nuances of different testing modalities currently being employed for this condition.
Quick identification and isolation of SARS-CoV-2 infected individuals is central to managing the COVID-19 pandemic. Real time reverse transcriptase PCR (rRT-PCR) is the gold standard for COVID-19 diagnosis. However, this resource-intensive and relatively lengthy technique is not ideally suited for mass testing. While pooled testing offers substantial savings in cost and time, the size of the optimum pool that offers complete concordance with results of individualized testing remains elusive. To determine the optimum pool size, we first evaluated the utility of pool testing using simulated 5-sample pools with varying proportions of positive and negative samples. We observed that 5-sample pool testing resulted in false negativity rate of 5% when the pools contained one positive sample. We then examined the diagnostic performance of 4-sample pools in the operational setting of a diagnostic laboratory using 500 consecutive samples in 125 pools. With background prevalence of 2.4%, this 4-sample pool testing showed 100% concordance with individualized testing and resulted in 66% and 59% reduction in resource and turnaround time, respectively. Since the negative predictive value of a diagnostic test varies inversely with prevalence, we re-tested the 4-sample pooling strategy using a fresh batch of 500 samples in 125 pools when the prevalence rose to 12.7% and recorded 100% concordance and reduction in cost and turnaround time by 36% and 30%, respectively. These observations led us to conclude that 4-sample pool testing offers the optimal blend of resource optimization and diagnostic performance across difference disease prevalence settings.
12 June 2024 in Journal of Ayurveda and Integrative Medicine
World health organization (WHO) recognizes antimicrobial resistance as a silent pandemic. It is estimated that 10 million deaths will occur annually due to antimicrobial resistant infections by 2050. Phytochemicals exhibit activity against drug resistant bacteria, offering potential for developing novel antibacterial agents. Garlic organosulphur compounds exhibit potent activity against a variety of drug-resistant bacteria. Identifying their mechanism of action is critical to assess their potential to be developed as novel antibacterial agents. Diallyl sulfide (DAS) is a component of garlic essential oil with antibacterial activity. In this study antibacterial activity of DAS was investigated against Bacillus cereus, a common foodborne pathogen. DAS exhibited activity against B. cereus with a minimum inhibitory concentration (MIC) of 54.75 mM. The presence of DAS significantly reduced the growth of B. cereus. The study also investigated the mechanism of antibacterial activity of DAS against B. cereus. Treating B. cereus with sub-MIC and MIC concentration of DAS resulted in a dose and time-dependent leakage of intracellular proteins. The protein leakage was enhanced at acidic pH. Scanning electron microscopy (SEM) of B. cereus treated with DAS showed deformation in the cell membrane. Thus, the data indicate that DAS exerts its antibacterial activity by compromising the membrane integrity of B. cereus. The study demonstrates DAS could be used to control B. cereus infections. The findings indicate that DAS has a membrane altering activity, suggesting that development of resistance to this mechanism is less likely and the compound could be novel antibacterial or a good adjuvant for antibiotics.