Adverse Influences of Antimicrobial Strategy against Mature Oral Biofilm

Antimicrobial measures, such as topical antiseptics and local drug delivery, have proven effective as complements to mechanical control. However, recent investigations have reported some adverse influences of antimicrobial strategy

Streptococcus pyogenes Phospholipase A2 Induces the Expression of Adhesion Molecules on Human Umbilical Vein Endothelial Cells and Aorta of Mice

The Streptococcus pyogenes phospholipase A2 (SlaA) gene is highly conserved in the M3 serotype of group A S. pyogenes, which often involves hypervirulent clones. However, the role of SlaA in S. pyogenes pathogenesis is unclear. Herein, we report that SlaA induces the expression of intercellular adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1) via the arachidonic acid signaling cascade. Notably, recombinant SlaA induced ICAM1 and VCAM1 expression in human umbilical vein endothelial cells (HUVECs), resulting in enhanced adhesion of human monocytic leukemia (THP-1) cells. However, C134A, a variant enzyme with no enzymatic activity, did not induce such events. In addition, culture supernatants from S. pyogenes SSI-1 enhanced the adhesion of THP-1 cells to HUVECs, but culture supernatants from the ΔslaA isogenic mutant strain had limited effects. Aspirin, a cyclooxygenase 2 inhibitor, prevented the adhesion of THP-1 cells to HUVECs and did not induce ICAM1 and VCAM1 expression in HUVECs treated with SlaA. However, zileuton, a 5-lipoxygenase inhibitor, did not exhibit such effects. Furthermore, pre-administration of aspirin in mice intravenously injected with SlaA attenuated the transcriptional abundance of ICAM1 and VCAM1 in the aorta. These results suggested that SlaA from S. pyogenes stimulates the expression of adhesion molecules in vascular endothelial cells. Thus, SlaA contributes to the inflammation of vascular endothelial cells upon S. pyogenes infection

Poor survival of Methicillin-resistantStaphylococcus aureuson inanimate objects in the public spaces

Photograph of a scene at the Cherokee Indian Village

Effect of <it>Porphyromonas gingivalis</it> infection on post-transcriptional regulation of the low-density lipoprotein receptor in mice

<p>Abstract</p> <p>Background</p> <p>Periodontal disease is suggested to increase the risk of atherothrombotic disease by inducing dyslipidemia. Recently, we demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9), which is known to play a critical role in the regulation of circulating low-density lipoprotein (LDL) cholesterol levels, is elevated in periodontitis patients. However, the underlying mechanisms of elevation of PCSK9 in periodontitis patients are largely unknown. Here, we explored whether <it>Porphyromonas gingivalis,</it> a representative periodontopathic bacterium, -induced inflammatory response regulates serum PCSK9 and cholesterol levels using animal models.</p> <p>Methods</p> <p>We infected C57BL/6 mice intraperitoneally with <it>Porphyromonas gingivalis</it>, a representative strain of periodontopathic bacteria, and evaluated serum PCSK9 levels and the serum lipid profile. PCSK9 and LDL receptor (LDLR) gene and protein expression, as well as liver X receptors (<it>Lxrs</it>), inducible degrader of the LDLR (<it>Idol</it>), and sterol regulatory element binding transcription factor (<it>Srebf</it>)<it>2</it> gene expression, were examined in the liver.</p> <p>Results</p> <p><it>P. gingivalis</it> infection induced a significant elevation of serum PCSK9 levels and a concomitant elevation of total and LDL cholesterol compared with sham-infected mice. The LDL cholesterol levels were significantly correlated with PCSK9 levels. Expression of the <it>Pcsk9</it>, <it>Ldlr</it>, and <it>Srebf2</it> genes was upregulated in the livers of the <it>P. gingivalis</it>-infected mice compared with the sham-infected mice. Although <it>Pcsk9</it> gene expression is known to be positively regulated by sterol regulatory element binding protein (SREBP)2 (human homologue of Srebf2), whereas <it>Srebf2</it> is negatively regulated by cholesterol, the elevated expression of <it>Srebf2</it> found in the infected mice is thought to be mediated by <it>P. gingivalis</it> infection.</p> <p>Conclusions</p> <p><it>P. gingivalis</it> infection upregulates PCSK9 production via upregulation of <it>Srebf2</it>, independent of cholesterol levels. Further studies are required to elucidate how infection regulates <it>Srebf2</it> expression and subsequently influences lipid metabolism.</p

Neutrophil Elastase Subverts the Immune Response by Cleaving Toll-Like Receptors and Cytokines in Pneumococcal Pneumonia

Excessive activation of neutrophils results in the release of neutrophil elastase (NE), which leads to lung injury in severe pneumonia. Previously, we demonstrated a novel immune subversion mechanism involving microbial exploitation of this NE ability, which eventually promotes disruption of the pulmonary epithelial barrier. In the present study, we investigated the effect of NE on host innate immune response. THP-1-derived macrophages were stimulated with heat-killed Streptococcus pneumoniae or lipopolysaccharide in the presence or absence of NE followed by analysis of toll-like receptor (TLR) and cytokine expression. Additionally, the biological significance of NE was confirmed in an in vivo mouse intratracheal infection model. NE downregulated the gene transcription of multiple cytokines in THP-1-derived macrophages through the cleavage of TLRs and myeloid differentiation factor 2. Additionally, NE cleaved inflammatory cytokines and chemokines. In a mouse model of intratracheal pneumococcal challenge, administration of an NE inhibitor significantly increased proinflammatory cytokine levels in bronchoalveolar lavage fluid, enhanced bacterial clearance, and improved survival rates. Our work indicates that NE subverts the innate immune response and that inhibition of this enzyme may constitute a novel therapeutic option for the treatment of pneumococcal pneumonia

Ozone ultrafine bubble water exhibits bactericidal activity against pathogenic bacteria in the oral cavity and upper airway and disinfects contaminated healthcare equipment

Ozone is strong oxidizing agent that is applied in aqueous form for sanitation. However, ozonated water is unstable and has a short half-life. Ultrafine bubble technology is promising to overcome these issues. Ultrafine bubble is nanoscale bubble and can exist in water for a considerable duration of time. This study aims to investigate the application of ozone ultrafine bubble water (OUFBW) as a disinfectant. We produced an OUFBW generator which generates OUFBW containing 4–6 ppm of ozone. Thereafter, we examined the bactericidal activity of the OUFBW against various pathogenic bacteria in oral cavity and upper airway, including antibiotic-susceptible and antibiotic-resistant Streptococcus pneumoniae, Pseudomonas aeruginosa, Streptococcus mutans, Streptococcus sobrinus, Fusobacterium nucleatum, Prevotella intermedia, and Porphyromonas gingivalis. Exposure of planktonic culture of these bacterial species to OUFBW reduced viable bacteria by > 99% within 30s. Additionally, OUFBW exerted bactericidal activity against S. pneumoniae and P. aeruginosa adhered to toothbrush and gauze, respectively. We also observed disruption of bacterial cell wall of S. pneumoniae exposed to OUFBW by transmission electron microscope. Additionally, OUFB did not show any significant cytotoxicity toward the human gingival epithelial cell line Ca9‐22. These results suggest that OUFBW exhibits bactericidal activity against broad spectrum of bacteria and has low toxicity towards human cells

Osteoimmunology in Periodontitis: Local Proteins and Compounds to Alleviate Periodontitis

Periodontitis is one of the most common oral diseases resulting in gingival inflammation and tooth loss. Growing evidence indicates that it results from dysbiosis of the oral microbiome, which interferes with the host immune system, leading to bone destruction. Immune cells activate periodontal ligament cells to express the receptor activator of nuclear factor kappa-B (NF-&kappa;B) ligand (RANKL) and promote osteoclast activity. Osteocytes have active roles in periodontitis progression in the bone matrix. Local proteins are involved in bone regeneration through functional immunological plasticity. Here, we discuss the current knowledge of cellular and molecular mechanisms in periodontitis, the roles of local proteins, and promising synthetic compounds generating a periodontal regeneration effect. It is anticipated that this may lead to a better perception of periodontitis pathophysiology