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Figure 3. p4 exhibits rapid concentration-dependent lytic activity against E. coli. A, E. coli HB101 was incubated with the indicated concentrations of p4 for 2 h. Cell viability was analyzed by MDA assay. n ϭ 3, mean Ϯ S.D. B, E. coli HB101 was incubated with 100 M p4 or vehicle for the indicated times. Cell viability was analyzed by MDA assay, n ϭ 3; mean Ϯ S.D. C, human erythrocytes were incubated with 1% Triton X-100, the indicated concentration of p4, or vehicle for 2 h. Hemolysis of erythrocytes is shown relative to lysis caused by Triton X-100. n ϭ 3, mean Ϯ S.D. D, E. coli HB101 was incubated with 100 M p4 or vehicle for the indicated times. Bacterial morphology was assessed by TEM. E, E. coli HB101 was incubated with 100 M p4 for 5 min. Alterations in bacterial permeability were visualized by fluorescence imaging. Bacteria were treated with FITC-labeled p4 (green), stained with PI (red), and counterstained with Hoechst to visualize DNA (blue). Arrows point to accumulation of p4 at the cell surface. F, ␤-galexpressing E. coli JM83 was incubated with the indicated concentrations of p4 for 15 min. The ␤-gal activity present in supernatants of p4-treated bacteria is shown as a percentage of the vehicle-treated bacteria. n ϭ 3, mean Ϯ S.D. G, E. coli HB101 was treated with p4 for 45 min, followed by TEM. Arrows and asterisks indicate outer membrane perturbations and the discontinuous inner membrane, respectively. H, intracellular localization of p4 is shown by immunogold labeling. E. coli HB101 was treated with biotin-p4 or p4 as a control, fixed, and stained with mouse anti-biotin Abs, followed by anti-mouse Abs conjugated to gold particles. Arrowheads indicate gold particles. The enlarged image (i) demonstrates interaction of p4 with the cell membrane. ***, p Ͻ 0.001; **, p Ͻ 0.01; *, p Ͻ 0.05 by Kruskal-Wallis one-way ANOVA with post hoc Dunn's test. TEM and fluorescence microscopy images are from one experiment and are representative of at least three experiments.

Periodontal inflammation is one of the most common chronic inflammatory conditions in humans. Despite recent advances in identifying and characterizing oral microbiota dysbiosis in the pathogenesis of gum disease, just how host factors maintain a healthy homeostatic oral microbial community or prevent the development of a pathogenic oral microbiota remains poorly understood. An important determinant of microbiota fate is local antimicrobial proteins. Here, we report that chemoattractant protein chemerin, which we recently identified as a potent endogenous antimicrobial agent in body barriers such as the skin, is present in the oral cavity under homeostatic and inflammatory conditions. Chemerin and a chemerin-derived antimicrobial peptide are bactericidal against select bacteria strategically positioned in dental biofilm. Gingival crevicular samples from patients with gingivitis but not periodontitis contain abundant bioactive chemerin capable of inducing CMKLR1-dependent leukocyte migration. Gingipains secreted by the periodontopathogen P. gingivalis inactivate chemerin. Together, these data suggest that as an antimicrobial agent and leukocyte chemoattractant, chemerin likely contributes to antimicrobial immune defense in the oral cavity.

Chronic inflammatory skin diseases like psoriasis alter the local skin microbiome and lead to complications such as persistent infection with opportunistic/pathogenic bacteria. Disease-associated changes in microbiota may be due to downregulation of epidermal antimicrobial proteins/peptides, such as antimicrobial protein chemerin. Here, we show that chemerin and its bioactive derivatives have differential effects on the viability of different genera of cutaneous bacteria. The lethal effects of chemerin are enhanced by bacterial-derived ROS-induced chemerin peptide oxidation and suppressed by stationary phase sigma factor RpoS. Insight into the mechanisms underlying changes in the composition of cutaneous bacteria during autoreactive skin disease may provide novel ways to mobilize chemerin and its peptide derivatives for maximum antimicrobial efficacy.

Host-microbiota interactions are bidirectional. On one hand, ecological pressures exerted by the host shape the composition and function of the microbiota. On the other, resident microbes trigger multiple pathways that influence the immunity of the host. Bile acids participate in both parts of this interplay. As host-derived compounds, they display bacteriostatic properties and affect the survival and growth of the members of the microbial community. As microbiota-modified metabolites, they further influence the microbiota composition and, in parallel, modulate the immunity of the host. Here, we provide a comprehensive overview of the mechanisms behind this unique dialogue and discuss how we can harness bile acids to treat intestinal inflammation.

Epithelia in the skin, gut and other environmentally exposed organs display a variety of mechanisms to control microbial communities and limit potential pathogenic microbial invasion. Naturally occurring antimicrobial proteins/peptides and their synthetic derivatives (here collectively referred to as AMPs) reinforce the antimicrobial barrier function of epithelial cells. Understanding how these AMPs are functionally regulated may be important for new therapeutic approaches to combat microbial infections. Some AMPs are subject to redox-dependent regulation. This review aims to: (i) explore cysteine-based redox active AMPs in skin and intestine; (ii) discuss casual links between various redox environments of these barrier tissues and the ability of AMPs to control cutaneous and intestinal microbes; (iii) highlight how bacteria, through intrinsic mechanisms, can influence the bactericidal potential of redox-sensitive AMPs.

Next-generation sequencing (NGS) technologies together with an improved access to compute performance led to a cost-effective genome sequencing over the past several years. This allowed researchers to fully unleash the potential of genomic and metagenomic analyses to better elucidate two-way interactions between host cells and microbiome, both in steady-state and in pathological conditions. Experimental research involving metagenomics shows that skin resident microbes can influence the cutaneous pathophysiology. Here, we review metagenome approaches to study microbiota at this barrier site. We also describe the consequences of changes in the skin microbiota burden and composition, mostly revealed by these technologies, in the development of common inflammatory skin diseases.

BackgroundThe O48 group comprises Salmonella bacteria containing sialic acid in the lipopolysaccharide (LPS). Bacteria with sialylated surface structures are described as pathogens that avoid immunological response of the host by making similar their surface antigens to the host’s tissues (molecular mimicry). It is known that the smooth-type LPS of Salmonella enterica and outer membrane proteins (OMP) PgtE, PagC and Rck mediate serum resistant phenotype by affecting complement system (C). The aim of this study was to investigate C3 component activation by Salmonella O48 LPS and OMP.FindingsIn the present study, we examined C3 component deposition on the three Salmonella O48 strains: S. enterica subspecies enterica serovar Ngozi, S. enterica subsp. enterica sv. Isaszeg, and S.enterica subsp. arizonae containing sialic acid in the O-specific part of LPS. The greatest C3 deposition occurred on Salmonella sv. Isaszeg cells (p < 0.005) as well as on their LPS (low content of sialic acid in LPS) (p < 0.05) after 45 min of incubation in 50% human serum. Weaker C3 deposition ratio on the Salmonella sv. Ngozi (high content of sialic acid in LPS) and Salmonella subsp. arizonae (high content of sialic acid in LPS) cells correlated with the lower C3 activation on their LPS. Immunoblotting revealed that OMP isolated from the tested strains also bound C3 protein fragments.ConclusionsWe suggest that activation of C3 serum protein is dependent on the sialic acid contents in the LPS as well as on the presence of OMP in the range of molecular masses of 35–48 kDa.