Patients with recurrent PVL+-Staphylococcus aureus infections show enhanced sensitivity to PVL-mediated formation of atypical NETs

Panton-Valentine leukocidin (PVL) is a Staphylococcus aureus (S. aureus) toxin that binds to and kills human neutrophils, resulting in the formation of neutrophil extracellular traps (NETs). Some individuals colonized with PVL-positive S. aureus (PVL-SA) suffer from recurring infections whereas others are asymptomatically colonized. We found that neutrophils from affected patients express higher levels of CD45, one of the PVL receptors, and are more susceptible to killing at a low concentration of recombinant PVL than control neutrophils. We verified that PVL induces the formation of NETs and provide genetic and pharmacological evidence that PVL-induced NET formation is independent of NADPH-oxidase and reactive oxygen species (ROS) production. Through NET proteome analysis we identified that the protein content of PVL-induced NETs is different from NETs induced by mitogen or the microbial toxin nigericin. The abundance of the proteins cathelicidin (CAMP), elastase (NE), and proteinase 3 (PRTN3) was lower on PVL-induced NETs, which were inefficient in killing S. aureus. Neutrophils from patients that suffer from recurring PVL-positive infections may be more sensitive to PVL-induced NET formation, which may impair their ability to combat the infection.

Footprints of a microbial toxin from the gut microbiome to mesencephalic mitochondria

ObjectiveIdiopathic Parkinson’s disease (PD) is characterised by alpha-synuclein (aSyn) aggregation and death of dopaminergic neurons in the midbrain. Recent evidence posits that PD may initiate in the gut by microbes or their toxins that promote chronic gut inflammation that will ultimately impact the brain. In this work, we sought to demonstrate that the effects of the microbial toxin β-N-methylamino-L-alanine (BMAA) in the gut may trigger some PD cases, which is especially worrying as this toxin is present in certain foods but not routinely monitored by public health authorities.DesignTo test the hypothesis, we treated wild-type mice, primary neuronal cultures, cell lines and isolated mitochondria with BMAA, and analysed its impact on gut microbiota composition, barrier permeability, inflammation and aSyn aggregation as well as in brain inflammation, dopaminergic neuronal loss and motor behaviour. To further examine the key role of mitochondria, we also determined the specific effects of BMAA on mitochondrial function and on inflammasome activation.ResultsBMAA induced extensive depletion of segmented filamentous bacteria (SFB) that regulate gut immunity, thus triggering gut dysbiosis, immune cell migration, increased intestinal inflammation, loss of barrier integrity and caudo-rostral progression of aSyn. Additionally, BMAA induced in vitro and in vivo mitochondrial dysfunction with cardiolipin exposure and consequent activation of neuronal innate immunity. These events primed neuroinflammation, dopaminergic neuronal loss and motor deficits.ConclusionTaken together, our results demonstrate that chronic exposure to dietary BMAA can trigger a chain of events that recapitulate the evolution of the PD pathology from the gut to the brain, which is consistent with ‘gut-first’ PD.

Modern and Classical Aspects on Infectious Diseases and their Management w.s.r. to Current Pandemic Situation: A Review

The ancient term Sankramaka Roga resembles communicable diseases as per modern science. These diseases mainly arise due to the influence of microbial invasion inside the body. The transmissions of such disease from one person to another take places via various means including Gatra Sansparsha, Prasnaga, sleeping and eating together; sharing objects and sexual contact, etc. The microbial toxin induces pathogenesis of infectious diseases after invasion of microorganism inside the body. Sankramaka Roga turned to Janapadodhwamsa if large numbers of people get affected, this condition can be correlated with resembles situation as per modern science. The modern science described uses of antibiotics and immune-therapy for the management of these diseases. Similarly Ayurveda rely on natural drugs, classical formulations, Panchakarma and Rasayana Chikitsa, etc. to treat Sankramaka Roga. Ayurveda concept of Ahara-Vihara, Dinacharya, Ratricharya, Ritucharya and Sadvritta improves immune system thus helps to prevent pathogenesis of Sankramaka Roga. Present article explores modern and classical aspects on infectious diseases and their management w.s.r. to current pandemic situation.

Botulism, gas gangrene, and clostridial gastrointestinal infections

Human botulism is caused by seven serological types of C. botulinum, which is ubiquitously distributed in the soil. Poisoning usually results from ingestion of preformed toxin in food, although this is rapidly inactivated at ordinary cooking temperatures, but it can also result from contaminated wounds. C. botulinum toxin binds irreversibly to the neuromuscular junction and is the most lethal known microbial toxin. There are five forms of clinical botulism: food-borne botulism; wound botulism; infant botulism; adult enteric infectious botulism; and inhalational botulism. Clinical presentation is with symptoms suggesting gastrointestinal tract illness, followed by neurological symptoms including diplopia, blurred vision, dizziness, and difficulty with speech or swallowing, leading on to generalized flaccid paralysis. The diagnosis can be confirmed by testing for botulinum toxin in the patient’s serum, urine, or stomach contents, or in the suspect food. Treatment requires supportive care, which may continue for many months.

Copper Utilization, Regulation, and Acquisition by Aspergillus fumigatus

Copper is an essential micronutrient for the opportunistic human pathogen, Aspergillus fumigatus. Maintaining copper homeostasis is critical for survival and pathogenesis. Copper-responsive transcription factors, AceA and MacA, coordinate a complex network responsible for responding to copper in the environment and determining which response is necessary to maintain homeostasis. For example, A. fumigatus uses copper exporters to mitigate the toxic effects of copper while simultaneously encoding copper importers and small molecules to ensure proper supply of the metal for copper-dependent processes such a nitrogen acquisition and respiration. Small molecules called isocyanides recently found to be produced by A. fumigatus may bind copper and partake in copper homeostasis similarly to isocyanide copper chelators in bacteria. Considering that the host uses copper as a microbial toxin and copper availability fluctuates in various environmental niches, understanding how A. fumigatus maintains copper homeostasis will give insights into mechanisms that facilitate the development of invasive aspergillosis and its survival in nature.

Selective assembly and functionalization of miniaturized redox capacitor inside microdevices for microbial toxin and mammalian cell cytotoxicity analyses

We report a novel strategy for bridging information transfer between electronics and biological systems within microdevices.