The aim of the present short communication is to shed a novel light on the auto immune disorder atopic dermatitis by discussing the possible role played by the plethora of toxic agents released by  Staphylococcus aureus which can act in a tight synergism with neutrophils derived cationic polyelectrolytes  as related to the pathogenesis of atopic dermatitis (AD) [1,2]. This disorder results in  inflammation of the  skin characterized by itchiness,  red  skin,  a  rash,  by   the  accumulations  of  large numbers of Staphylococcus  aureus  their toxins [2] and pro- inflammatory agents secreted by migrating neutrophiles [3], are considered the main cause of AD pathogenicity.

Catalase-negative penicillin-sensitive group A hemolytic streptococci (GAS) are multifactorial microorganisms, which do not produce a unique damage-associated molecular patterns which if effectively neutralized might effectively stop their pathogenicity. GAS is involved in the pathogenicity of pharangitis, tonsillitis, rheumatic fever, arthritis, necrotizing fasciitis (NF), toxic shock syndrome and also in sepsis. GAS-induced NF is quite a rare but dangerous and deadly infection, which most commonly occurs in the arms, legs and abdominal wall and is fatal in 30%-40% of cases. GAS, which possess surface capsular polysaccharide and antigenic M and T proteins, arrive at the inflammatory areas by generating spreading factors such as hyaluronidase, DNase and streptokinaseactivated plasmin. GAS can spread in tissues and avidly adhere to membranes of target cells to deliver a nonimmunogenic cell bound hemolysin (CBH) upon cells’ membrane phospholipids to induce a penetrating membrane damage (“a kiss of Death”). Two additional potent extracellular hemolysins, Streptolysin O (SLO) and a nonimmunogenic streptolysin S (SLS) produced can injure neutrophils (PMNs), which are recruited to the infected sites in large numbers. However, PMNs can engage in phagocytosis and also undergo activation to release various proinflammatory agents including NADPH-generated superoxide which dismutates to H2 O2 and with myeloperoxidase (MPO) which forms toxic HOCl upon interaction with halides. Activated PMNs also deliver highly cationic peptides such as LL37, cationic elastase, cathepsins and nuclear histone, which interact electrostatically with negatively-charged membrane sites forming membrane lesions. PMNs also secrete many acid hydrolases, several Th1 cytokines and chemokines, which recruit more PMNs. Similarly, to beta-lactams antibiotics, cationic peptides can also activate bacteriolysis and trigger the release of the pro-inflammatory agents lipoteichoic acid (LTA) and peptidoglycan (PPG). We hereby propose that in infectious and inflammatory sites GAS and PMNs exo-products and also microbial cellwall structures might all act synergistically to cause cell and tissue damage. Cell damage might be ameliorated by appropriate cocktails of anti-inflammatory agents. also, containing highly negatively charged heparin 23.

Abstract: We postulate that the extensive cell and tissue damage inflicted by many infectious, inflammatory and post-inflammatory episodes is an enled result of a synergism among the invading microbial agents, host neutrophils and dead and dying cells in the nidus. Microbial toxins and other metabolites along with the plethora of pro-inflammatory agents released from activated neutrophils massively recruited to the infectious sites and high levels of cationic histones, other cationic peptides, proteinases and Th1 cytokines released from activated polymorphonuclear neutrophils (PMNs) and from necrotized tissues may act in concert (synergism) to bring about cell killing and tissue destruction. Multiple, diverse interactions among the many potential pro-inflammatory moieties have been described in these complex lesions. Such infections are often seen in the skin and aerodigestive tract where the tissue is exposed to the environment, but can occur in any tissue. Commonly, the tissue-destructive infections are caused by group A streptococci, pneumococci, Staphylococcus aureus, meningococci, Escherichia coli and Shigella, although many other microbial species are seen on occasion. All these microbial agents are characterized by their ability to recruit large numbers of PMNs. Given the complex nature of the disease process, it is proposed that, to treat these multifactorial disorders, a “cocktail” of anti-inflammatory agents combined with non-bacteriolytic antibiotics and measures to counteract the critical toxic role of cationic moieties might prove more effective than a strategy based on attacking the bacteria alone.

Background:Streptococcus mutans (S. mutans) and Candida albicans (C. albicans) are two major contributors to dental caries. They have a symbiotic relationship, allowing them to create an enhanced biofilm. Our goal was to examine whether two natural polyphenols (Padma hepaten (PH) and a polyphenol extraction from green tea (PPFGT)) could inhibit the caries-inducing properties of S. mutans and C. albicans. Methods: Co-species biofilms of S. mutans and C. albicans were grown in the presence of PH and PPFGT. Biofilm formation was tested spectrophotometrically. Exopolysaccharides (EPS) secretion was quantified using confocal scanning laser microscopy. Biofilm development was also tested on orthodontic surfaces (Essix) to assess biofilm inhibition ability on such an orthodontic appliance. Results: PPFGT and PH dose-dependently inhibited biofilm formation without affecting the planktonic growth. We found a significant reduction in biofilm total biomass using 0.625 mg/mL PPFGT and 0.16 mg/mL PH. A concentration of 0.31 mg/mL PPFGT and 0.16 mg/mL PH inhibited the total cell growth by 54% and EPS secretion by 81%. A reduction in biofilm formation and EPS secretion was also observed on orthodontic PVC surfaces. Conclusions: The polyphenolic extractions PPFGT and PH have an inhibitory effect on S. mutans and C. albicans biofilm formation and EPS secretion.