Cationic peptides from leukocytes might kill bacteria by activating their autolytic enzymes causing bacteriolysis: why are publications proposing this concept never acknowledged?

A large series of publications 1-9 has proposed that cationic peptides from leukocytes kill bacteria primarily by causing a depolarization of their membranes leading to enhanced permeability. One group of cationic peptides from human neutrophils was even coined bacteri-cidal/permeability-increasing proteins. 3 Surprisingly, however, none of a large series of other publications that had proposed a concept that cationic agents from neutrophils might be bactericidal also by virtue of their capacity to activate the bacterial autolytic wall enzymes (muramidases), leading to bacteriolysis and cell death, 10-22 has ever been cited in any of the publications by the leading authors in this field of research. 1-9 For the information of your readers, there exist a series of 16 publications since 1974 entitled " Effect of leukocyte hydrolases on bacteria " and several additional publications on the same subject under different titles, many of them published in journals covered by Medline; the references contain a selected list of these. 10-22,24 These had proposed that many of the highly cationic agents either present in plasma or generated by activated phagocytes (eg, lysozymes, PLA2, elastase, cathepsin G, myeloperoxidase, bactericidal/permeability-increasing proteins, defensins, etc) might kill bacteria not simply by acting on the membranes to cause depolarization and enhanced permeability 1-7 but also by an indirect mechanism. This involves a deregulation, by the cationic agents, of the anionic and amphiphilic regulators of the autolytic wall enzymes (muramidases) (lipoteichoic acid in Gram-positives and Forssman antigens in Gram-negatives) 16,17,23-25 resulting in hydrolysis of the peptidoglycan, in bacteriolysis, and in cell death. It is of great clinical importance that the bacteriolysis-inducing activity of cationic agents mimics that of beta-lactam antibiotics. 26 Furthermore, the observations that a variety of highly negatively charged, sulfated anionic agents can act as potent inhibitors of the cationic agent– and beta-lactam–induced bacteriolysis 11,12,14,16,17,27-30 further stress the importance of the autolytic systems in bacterial killing. This phenomenon might also be of great clinical significance especially in selecting measures to control postin-fectious sequelae that undoubtedly are triggered by the release of bacterial components, especially following bacteriolysis. Regrettably, attempts to bring these issues to the awareness of the leading investigators in the field of cationic proteins 1-9 and of clinicians involved is the clinical aspects of sepsis control have not been successful. If the concept that cationic agents might be bactericidal also because of their bacteriolysis-inducing properties is reasonable and scientifically sound, it is expected that publications describing this …