ARS-CoV-2 was first detected in December 2019, leading to a pandemic with an estimated 5-6% mortality rate 1. Akin to SARS-CoV-1, the causative agent of the 2003 SARS outbreak, this is an enveloped betacoronavirus with protrusions of large trimeric 'spike' proteins. Receptor binding domains (RBDs) located at the tips of these spikes facilitate host cell entry via interaction with angiotensin-converting enzyme 2 (ACE2) 2. Spikes are type I transmembrane glycoproteins, formed from a single polypeptide, which transitions into a post-fusion state via cleavage into S1 (N-terminal) and S2 (C-terminal) chains following receptor binding or trypsin treatment 3. In the pre-fusion state, the apical RBD (~22 kDa) is folded down, enshrouded by the N-terminal domain (NTD) of the spike so that the receptor binding site is inaccessible until, it is assumed, an RBD stochastically swings upwards to present the ACE2 binding site 4-7. ACE2 interaction locks the RBD in the 'up' conformation, which drives conversion to the post-fusion form where the S2 subunit engages the host membrane while dispensing with S1 4,5. Neutralizing human monoclonal antibodies (mAbs) that recognize the ACE2 receptor binding site for SARS-CoV-1 and SARS-CoV-2 are generally not cross-reactive between the two viruses and are susceptible to escape mutation 8-12. Indeed, a natural mutation (Y495N) has already been identified at this site (GISAID 13 : accession ID: EPI_ISL_429783 Wienecke-Baldacchino et al.). By contrast, the CR3022 antibody (derived from a SARS-CoV-1-infected patient) cross-reacts strongly with SARS-CoV-2 (see Methods and Fig. 1) and has been shown to recognize a cryptic, conserved footprint on the RBD distinct from the binding epitope of

To infect an animal host, Salmonella enterica serovar Typhimurium must penetrate the intestinal epithelial barrier. This process of invasion requires a type III secretion system encoded within Salmonella pathogenicity island I (SPI1). We found that a mutant with deletions of the acetate kinase and phosphotransacetylase genes (ackA-pta) was deficient in invasion and SPI1 expression but that invasion gene expression was completely restored by supplying medium conditioned by growth of the wild-type strain, suggesting that a signal produced by the wild type, but not by the ackA-pta mutant, was required for invasion. This mutant also excreted 68-fold-less formate into the culture medium, and the addition of sodium formate to cultures restored both the expression of SPI1 and the invasion of cultured epithelial cells by the mutant. The effect of formate was pH dependent, requiring a pH below neutrality, and studies in mice showed that the distal ileum, the preferred site of Salmonella invasion in this species, had the appropriate formate concentration and pH to elicit invasion, while the cecum contained no detectable formate. Furthermore, we found that formate affected the major regulators of SPI1, hilA and hilD, but that the primary routes of formate metabolism played no role in its activity as a signal.

This study tested the feasibility of a high throughput metagenomic approach to analyze the pre- and posttreatment of subgingival plaque in two subjects with aggressive periodontitis. DNA was extracted from subgingival samples and subjected to PCR amplification of the c2-c4 regions of the 16S rDNA using primers with bar codes to identify individual samples. The PCR products were pooled and sequenced for the v4 region of the 16S rDNA using the 454 FLX standard platform. The results were analyzed for species/phylotypes in the Human Oral Microbiome Database (HOMD) and Ribosomal Database Project (RDP) database. The sequencing of the amplicons resulted in 24,673 reads and identified 208 species/phylotypes. Of those, 129 species/phylotypes were identified in both patients but their proportions varied. While >120 species/phylotypes were identified in all samples, 28-42 species/phylotypes cumulatively represent 90% of all subgingival bacteria in each sample. The remaining species/phylotypes each constituted ≤0.2% of the total subgingival bacteria. In conclusion, the subgingival microbiota are characterized by high species richness dominated by a few species/ phylotypes. The microbiota changed after periodontal therapy. High throughput metagenomic analysis is applicable to assess the complexity and changes of the subgingival microbiota.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that was traditionally thought to be closely related to genetic and environmental risk factors. Although treatment options for SLE with hormones, immunosuppressants, and biologic drugs are now available, the rates of clinical response and functional remission of these drugs are still not satisfactory. Currently, emerging evidence suggests that gut microbiota dysbiosis may play crucial roles in the occurrence and development of SLE, and manipulation of targeting the gut microbiota holds great promises for the successful treatment of SLE. The possible mechanisms of gut microbiota dysbiosis in SLE have not yet been well identified to date, although they may include molecular mimicry, impaired intestinal barrier function and leaky gut, bacterial biofilms, intestinal specific pathogen infection, gender bias, intestinal epithelial cells autophagy, and extracellular vesicles and microRNAs. Potential therapies for modulating gut microbiota in SLE include oral antibiotic therapy, fecal microbiota transplantation, glucocorticoid therapy, regulation of intestinal epithelial cells autophagy, extracellular vesicle-derived miRNA therapy, mesenchymal stem cell therapy, and vaccination. This review summarizes novel insights into the mechanisms of microbiota dysbiosis in SLE and promising therapeutic strategies, which may help improve our understanding of the pathogenesis of SLE and provide novel therapies for SLE.