Type-IVC Secretion System: A Novel Subclass of Type IV Secretion System (T4SS) Common Existing in Gram-Positive Genus <em>Streptococcus</em>

<div><p>A growing number of pathogens are being found to possess specialized secretion systems which they use in various ways to subvert host defenses. Type IV secretion system (T4SS) is one of versatile secretion systems essential for the virulence and even survival of some bacteria species, and they enable the secretion of protein and DNA substrates across the cell envelope. T4SS was once believed to be present only in Gram-negative bacteria. In this study, we present evidence of a new subclass of T4SS, Type-IVC secretion system and indicate its common existence in the Gram-positive bacterial genus <em>Streptococcus.</em> We further identified that VirB1, VirB4, VirB6 and VirD4 are the minimal key components of this system. Using genome comparisons and evolutionary relationship analysis, we proposed that Type-IVC secretion system is movable via transposon factors and mediates the conjugative transfer of DNA, enhances bacterial pathogenicity, and could cause large-scale outbreaks of infections in humans.</p> </div

List of <i>Streptococcus</i> strains with whole genomes used in the current study.

<p>List of <i>Streptococcus</i> strains with whole genomes used in the current study.</p

Genetic organization of T4SS.

<p>For <i>A. tumefaciens</i>, gene names B = <i>virB</i> and D4 = <i>virD4</i>. For <i>L. pneumophila,</i> upper-case gene names = <i>dot</i> and lower-case gene names = <i>icm</i>. Genes in orange correspondents to periplasmic lytic transglycosylase, in green ATPase, in yellow T pilus, in red channel subunit across inner membrane, in blue channel subunit across outer membrane, in grey no T4SS genes or genes with the unclear function.</p

The phylogenetic tree.

<p>(A) The neighbor-joining (NJ) tree obtained on the basis of the housekeeping gene <i>rpoB</i>. The red solid circles represent GIs with <i>virB/D</i> clusters. (B) NJ tree obtained on the basis of a concatenated sequence of <i>virB4</i>, <i>virB6</i>, and <i>virD4</i> genes in GI.</p

Hypothetical model for Type-IVC secretion system.

<p>The colored parts are the components of the Type-IVC secretion system system. The grey parts are objects present in the canonical T4SS of Gram-negative strains but lost in the Gram-positive Type-IVC secretion system, e.g., the outer membrane, VirB2, and VirB5.</p

Carbohydrate-Functionalized Chitosan Fiber for Influenza Virus Capture

The high transmissibility and genetic variability of the influenza virus have made the design of effective approaches to control the infection particularly challenging. The virus surface hemagglutinin (HA) protein is responsible for the viral attachment to the host cell surface via the binding with its glycoligands, such as sialyllactose (SL), and thereby is an attractive target for antiviral designs. Herein we present the facile construction and development of two SL-incorporated chitosan-based materials, either as a water-soluble polymer or as a functional fiber, to demonstrate their abilities for viral adhesion inhibition and decontamination. The syntheses were accomplished by grafting a lactoside bearing an aldehyde-functionalized aglycone to the amino groups of chitosan or chitosan fiber followed by the enzymatic sialylation with sialyltransferase. The obtained water-soluble SL–chitosan conjugate bound HA with high affinity and inhibited effectively the viral attachment to host erythrocytes. Moreover, the SL-functionalized chitosan fiber efficiently removed the virus from an aqueous medium. The results collectively demonstrate that these potential new materials may function as the virus adsorbents for prevention and control of influenza. Importantly, these materials represent an appealing approach for presenting a protein ligand on a chitosan backbone, which is a versatile molecular platform for biofunctionalization and, thereby, can be used for not only antiviral designs, but also extensive medical development such as diagnosis and drug delivery

Glycosylated Enfuvirtide: A Long-Lasting Glycopeptide with Potent Anti-HIV Activity

Many peptide-based therapeutics have short circulatory half-lives. We report here that the pharmacokinetics of an anti-HIV peptide drug enfuvirtide (ENF) can be dramatically improved by a chemical glycosylation approach. A set of glycosylated ENFs with varying glycosylation sites and glycan structures were synthesized. Among these, a sialic acid-introduced peptide (SL-ENF) demonstrated a 15-fold extended half-life in rats relative to ENF (<i>T</i>_1/2: 23.1 vs 1.5 h), and its antiviral potency was comparable to that of ENF (EC₅₀: 2 vs 3 nM). SL-ENF bound to a functional fragment of the HIV fusogenic protein gp41 and formed complexes with high affinity and α-helicity, revealing the mechanism behind its potent antiviral activity. Because it is widely accepted in biology that glycosylation protects proteins from denaturation and proteases, our approach may be useful for the development of novel protein and peptide drugs with enhanced pharmaceutical properties

Partial contributions of six exploratory variables with confidence bands.

<p>A: Population density; B: Gross Domestic Product (GDP) per capita; C: Road density; D: Normalized Difference Vegetation Index (NDVI); E: Street/town at the prefectural boundary; F: Rural and urban). Smoothed functions (solid line) are bounded by 95% point wise standard errors (dashed lines for curves).</p

Study area.

<p>Study area.</p

Approximate significance of smooth terms of the negative binomial GAM model.

<p>Note: Values in bold font were significant at the 0.001 level</p><p>edf >1 indicate nonlinear relationships</p><p>Approximate significance of smooth terms of the negative binomial GAM model.</p