A Model for SARS-CoV-2 Infection with Treatment

The current emergence of coronavirus (SARS-CoV-2) puts the world in threat. The structural research on the receptor recognition by SARS-CoV-2 has identified the key interactions between SARS-CoV-2 spike protein and its host (epithelial cell) receptor, also known as angiotensin-converting enzyme 2 (ACE2). It controls both the cross-species and human-to-human transmissions of SARS-CoV-2. In view of this, we propose and analyze a mathematical model for investigating the effect of CTL responses over the viral mutation to control the viral infection when a postinfection immunostimulant drug (pidotimod) is administered at regular intervals. Dynamics of the system with and without impulses have been analyzed using the basic reproduction number. This study shows that the proper dosing interval and drug dose both are important to eradicate the viral infection.

Reduced Susceptibility of Coronavirus SARS Development After Earthing Due to Increased pH Values in the Respiratory Tract

Background: Low pH is an important factor facilitating entry of enveloped viruses including coronaviruses and further fusion with the host epithelial cell membrane. pH in the pulmonary environment can be maintained by supplying a negative electric charge. The main objective was to check if earthing (direct or indirect connection to Earth) changes the pH of the respiratory tract.Methods: Nine participants were evaluated and pH measurements were taken on the mucous membrane of the throat before and after 15 minutes of earthing.Results: Mean pH before earthing was 5.83±0.43 and after earthing was 6.33± 0.43 (p=0.000323). Conclusions: Earthing is able to supply a negative charge resulting in alkalization of the pulmonary environment. The increased pH value in the respiratory tract reduces the pH-dependent entry of coronaviruses into epithelial cells. Earthing can have an impact on the course of respiratory tract infection both viral and bacterial decreasing the susceptibility of the development of fatal forms of SARS (Severe Acute Respiratory Syndrome).

Molecular evolution of the VacA p55 binding domain of Helicobacter pylori in mestizos from a high gastric cancer region of Colombia

The stomach bacterium Helicobacter pylori is one of the most prevalent pathogens in humans, closely linked with serious diseases such as gastric cancer. The microbe has been associated with its host for more than 100,000 years and escorted modern humans out of Africa. H. pylori is predominantly transmitted within families and dispersed globally, resulting in distinct phylogeographic patterns, which can be utilized to investigate migrations and bioturbation events in human history. Latin America was affected by several human migratory waves due to the Spanish colonisation that drastically changed the genetic load and composition of the bacteria and its host. Genetic evidence indicates that independent evolutionary lines of H. pylori have evolved in mestizos from Colombia and other countries in the region during more than 500 years since colonisation. The vacuolating cytotoxin VacA represents a major virulence factor of the pathogen comprising two domains, p33 and p55, the latter of which is essential for binding to the host epithelial cell. The evolution of the VacA toxin in Colombia has been strongly biased due to the effects of Spanish colonization. However, the variation patterns and microevolution of the p55 domain have not yet been described for this population. In the present study, we determined the genetic polymorphisms and deviations in the neutral model of molecular evolution in the p55 domain of 101 clinical H. pylori isolates collected in Bogotá, a city located in Andean mountains characterized by its high gastric cancer risk and its dominant mestizo population. The microevolutionary patterns of the p55 domain were shaped by recombination, purifying and episodic diversifying positive selection. Furthermore, amino acid positions 261 and 321 in the p55 domain of VacA show a high variability among mestizos clinical subsets, suggesting that natural selection in H. pylori may operate differentially in patients with different gastric diseases.

A phylogenomic view of ecological specialization in the Lachnospiraceae, a family of digestive tract-associated bacteria

Several bacterial families are known to be highly abundant within the human microbiome, but their ecological roles and evolutionary histories have yet to be investigated in depth. One such family, Lachnospiraceae (phylum Firmicutes, class Clostridia) is abundant in the digestive tracts of many mammals and relatively rare elsewhere. Members of this family have been linked to obesity and protection from colon cancer in humans, mainly due to the association of this group with the production of butyric acid, a substance that is important for both microbial and host epithelial cell growth. We examined the genomes of 30 Lachnospiraceae isolates to better understand the phylogenetic relationships and basis of ecological differentiation within this group. Although this family is often used as an indicator of butyric acid production, fewer than half of the examined genomes contained genes from either of the known pathways that produce butyrate, with the distribution of this function likely arising in part from lateral gene transfer. An investigation of environment-specific functional signatures indicated that human gut-associated Lachnospiraceae possessed genes for endospore formation while other members of this family lacked key sporulation-associated genes, an observation supported by analysis of metagenomes from the human gut, oral cavity and bovine rumen. Our analysis demonstrates that despite a lack of agreement between Lachnospiraceae phylogeny and assigned habitat there are several examples of genetic signatures of habitat preference derived from both lateral gene transfer and gene loss.

A phylogenomic view of ecological specialization in the Lachnospiraceae, a family of digestive tract-associated bacteria

Several bacterial families are known to be highly abundant within the human microbiome, but their ecological roles and evolutionary histories have yet to be investigated in depth. One such family, Lachnospiraceae (phylum Firmicutes, class Clostridia) is abundant in the digestive tracts of many mammals and relatively rare elsewhere. Members of this family have been linked to obesity and protection from colon cancer in humans, mainly due to the association of this group with the production of butyric acid, a substance that is important for both microbial and host epithelial cell growth. We examined the genomes of 30 Lachnospiraceae isolates to better understand the phylogenetic relationships and basis of ecological differentiation within this group. Although this family is often used as an indicator of butyric acid production, fewer than half of the examined genomes contained genes from either of the known pathways that produce butyrate, with the distribution of this function likely arising in part from lateral gene transfer. An investigation of environment-specific functional signatures indicated that human gut-associated Lachnospiraceae possessed genes for endospore formation while other members of this family lacked key sporulation-associated genes, an observation supported by analysis of metagenomes from the human gut, oral cavity and bovine rumen. Our analysis demonstrates that despite a lack of agreement between Lachnospiraceae phylogeny and assigned habitat there are several examples of genetic signatures of habitat preference derived from both lateral gene transfer and gene loss.

Prebiotic Galactooligosaccharides Reduce Adherence of Enteropathogenic Escherichia coli to Tissue Culture Cells

ABSTRACT Prebiotic oligosaccharides are thought to provide beneficial effects in the gastrointestinal tract of humans and animals by stimulating growth of selected members of the intestinal microflora. Another means by which prebiotic oligosaccharides may confer health benefits is via their antiadhesive activity. Specifically, these oligosaccharides may directly inhibit infections by enteric pathogens due to their ability to act as structural mimics of the pathogen binding sites that coat the surface of gastrointestinal epithelial cells. In this study, the ability of commercial prebiotics to inhibit attachment of microcolony-forming enteropathogenic Escherichia coli (EPEC) was investigated. The adherence of EPEC strain E2348/69 on HEp-2 and Caco-2 cells, in the presence of fructooligosaccharides, inulin, galactooligosaccharides (GOS), lactulose, and raffinose was determined by cultural enumeration and microscopy. Purified GOS exhibited the greatest adherence inhibition on both HEp-2 and Caco-2 cells, reducing the adherence of EPEC by 65 and 70%, respectively. In addition, the average number of bacteria per microcolony was significantly reduced from 14 to 4 when GOS was present. Adherence inhibition by GOS was dose dependent, reaching a maximum at 16 mg/ml. When GOS was added to adhered EPEC cells, no displacement was observed. The expression of BfpA, a bundle-forming-pilus protein involved in localized adherence, was not affected by GOS, indicating that adherence inhibition was not due to the absence of this adherence factor. In addition, GOS did not affect autoaggregation. These observations suggest that some prebiotic oligosaccharides may have antiadhesive activity and directly inhibit the adherence of pathogens to the host epithelial cell surface.