Can hemolytic streptococci be considered “forefathers” of modern phagocytes? Both cell types freely migrate in tissues and destroy host cells by a “synergistic cross-talk” among their secreted agonists

Gamma globulin, Evan's blue, aprotinin A PLA2inhibitor, tetracycline and antioxidants protect epithelial cells against damage induced by synergism among streptococcal hemolysins, oxidants and proteinases: relation to the prevention of post-streptococcal sequelae and septic shock

“…These studies also showed that the potent antioxidant systems present in a variety of mammalian cells, grown in culture, could be readily overcome if sublytic amounts of oxidants were combined with subtoxic amounts of a variety membrane‐damaging agents and with proteases (a distinct synergistic effect). Our studies have also pointed out that there is a striking similarity between the strategies by which the highly invasive and catalase‐negative microorganisms (hemolytic streptococci, Clostridia) and activated phagocytes (neutrophils, macrophages) injure host cells during infection and inflammation (an evolution phenomenon) [9]. Both bacteria and phagocytes pave their ways in tissues by spreading enzymes and kill targets most efficiently and in a synergistic manner especially after binding to their surfaces (‘a kiss of death’) where they can directly deliver toxic agents.…”

“…Since combinations among oxidants, membrane‐perforating agents and proteinases were found to act synergistically to injure endothelial cells, epithelial cells and beating heart cells [1–10] and since both streptolysins O (SLO) and S (SLS) are potent cytotoxic agents [11–13], we examined the toxic effects of combinations either of EXPA or of EXPC (both containing high SLO activities), with oxidants and proteinases. Fig.…”

“…It has been suggested that the main mechanisms by which mammalian cells are injured in infectious and inflammatory processes might involve a coordinated synergistic ‘cross‐talk’ among reactive oxygen species (ROS), membrane‐perforating enzymes and cationic proteins, microbial hemolysis, fatty acids, proteinases, and cytokines [1–10]. These agents might be elaborated either by microorganisms, or by the hosts own defense systems.…”

Can we learn from the pathogenetic strategies of group A hemolytic streptococci how tissues are injured and organs fail in post-infectious and inflammatory sequelae?

“…What makes streptococci so versatile is still enigmatic. However, the possibility that tissue injury following severe streptococcal infections might be induced not only as a result of synergism among their own metabolites, toxins and cell wall components, but mainly when these agents engage in a deleterious ‘synergistic cross‐talk’ with the host's own defense systems, is paradoxical, but also highly realistic [2,11–14]. It is also important to note that an effective prevention of post‐infectious and inflammatory sequelae, whether caused by Gram‐positive or by Gram‐negative bacteria, might depend on the development of adequate, quick, and inexpensive predictive markers, either in the outpatient clinic or at the bedside, which might herald their invasion of the bloodstream.…”

“…Hemolytic streptococci also share common antigens with the human heart, kidney, connective tissue and brain (molecular mimicry) which might explain some of the autoimmune features of post‐streptococcal sequelae. These observations led us to speculate that these microbial species and perhaps also certain of the Gram‐negative toxigenic bacteria might perhaps be considered some kind of ‘forefathers’ of modern phagocytes (a converging evolutional phenomenon which does not necessarily involve the generation of identical gene products) [12].…”