Penicillin-binding protein inactivation by human neutrophil myeloperoxidase.

Rakita, Robert M.; Rosen, Henry

doi:10.1172/jci115372

Cited by 12 publications

(8 citation statements)

References 27 publications

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“…A variety of putative inhibitors (dashed arrows) against the various pro‐inflammatory agonists, might be beneficial to attenuate the deleterious sequelae of severe microbial infections (see refs. 1, 2, 15, 20, 21, 37–39, 52, 55, 63, 69, 73, 131–134).…”

Section: B What Triggers Bacteriolysis?mentioning

confidence: 99%

The role of bacteriolysis in the pathophysiology of inflammation, infection and post‐infectious sequelae

Ginsburg

2002

APMIS

114

102

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The literature dealing with the biochemical basis of bacteriolysis and its role in inflammation, infection and in post-infectious sequelae is reviewed and discussed. Bacteriolysis is an event that may occur when normal microbial multiplication is altered due to an uncontrolled activation of a series of autolytic cell-wall breaking enzymes (muramidases). While a low-level bacteriolysis sometimes occurs physiologically, due to "mistakes" in cell separation, a pronounced cell wall breakdown may occur following bacteriolysis induced either by beta-lactam antibiotics or by a large variety of bacteriolysis-inducing cationic peptides. These include spermine, spermidine, bactericidal peptides defensins, bacterial permeability increasing peptides from neutrophils, cationic proteins from eosinophils, lysozyme, myeloperoxidase, lactoferrin, the highly cationic proteinases elastase and cathepsins, PLA2, and certain synthetic polyamino acids. The cationic agents probably function by deregulating lipoteichoic acid (LTA) in Gram-positive bacteria and phospholipids in Gram-negative bacteria, the presumed regulators of the autolytic enzyme systems (muramidases). When bacteriolysis occurs in vivo, cell-wall- and -membrane-associated lipopolysaccharide (LPS (endotoxin)), lipoteichoic acid (LTA) and peptidoglycan (PPG), are released. These highly phlogistic agents can act on macrophages, either individually or in synergy, to induce the generation and release of reactive oxygen and nitrogen species, cytotoxic cytokines, hydrolases, proteinases, and also to activate the coagulation and complement cascades. All these agents and processes are involved in the pathophysiology of septic shock and multiple organ failure resulting from severe microbial infections. Bacteriolysis induced in in vitro models, either by polycations or by beta-lactams, could be effectively inhibited by sulfated polysaccharides, by D-amino acids as well as by certain anti-bacteriolytic antibiotics. However, within phagocytic cells in inflammatory sites, bacteriolysis tends to be strongly inhibited presumably due to the inactivation by oxidants and proteinases of the bacterial muramidases. This might results in a long persistence of non-biodegradable cell-wall components causing granulomatous inflammation. However, persistence of microbial cell walls in vivo may also boost innate immunity against infections and against tumor-cell proliferation. Therapeutic strategies to cope with the deleterious effects of bacteriolysis in vivo include combinations of autolysin inhibitors with combinations of certain anti-inflammatory agents. These might inhibit the synergistic tissue- and- organ-damaging "cross talks" which lead to septic shock and to additional post-infectious sequelae.

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Section: B What Triggers Bacteriolysis?mentioning

confidence: 99%

The role of bacteriolysis in the pathophysiology of inflammation, infection and post‐infectious sequelae

Ginsburg

2002

APMIS

114

102

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“…HOCl-induced lysis was only slightly delayed by adding glucose to the medium, indicating that lytic injury is not ameliorated by GSH. enzymes and membrane transporters were inactivated by HOCl [12,19,24,25]. In cultured tumour cells, HOCl caused disturbance of various plasma-membrane functions and this was attributed to membrane protein thiol oxidation [18].…”

Section: Introductionmentioning

confidence: 99%

Oxidation of intracellular glutathione after exposure of human red blood cells to hypochlorous acid

Vissers

Winterbourn

1995

Biochemical Journal

123

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Exposure of human red blood cells to low doses of hypochlorous acid (HOCl) resulted in the loss of intracellular GSH. Oxidation occurred less than 2 min after the addition of HOCl, and required approx. 2.5 mol of HOCl per mol of GSH lost. Loss of GSH preceded oxidation of membrane thiols, the formation of chloramines and haemoglobin oxidation. The susceptibility of intracellular GSH to oxidation by HOCl was two-thirds that of GSH in cell lysates. These results indicate that HOCl can penetrate the red cell membrane, which provides little barrier protection for cytoplasmic components, and that GSH oxidation by HOCl may be a highly selective process. Virtually all of the GSH lost was converted into GSSG. If glucose was added to the medium, most of the GSH oxidized by low doses of HOCl was rapidly regenerated. At higher doses, recovery was less efficient. However, when HOCl was added as a slow infusion rather than in a single bolus, there was increased recovery at higher doses. This indicates that in metabolically active cells regeneration is rapid and GSH may protect cell components from damage by HOCl. HOCl-induced lysis was only slightly delayed by adding glucose to the medium, indicating that lytic injury is not ameliorated by GSH.

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“…This contributed to the persistence of nondegraded microbial components, leading to unbalanced bacterial growth and cell death. 42 , 43 …”

Section: Polycations and Lysozyme As Activators Of Autolytic Wall Enzmentioning

confidence: 99%

From amino acids polymers, antimicrobial peptides, and histones, to their possible role in the pathogenesis of septic shock: a historical perspective

Ginsburg

Heerden

Koren

2017

JIR

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This paper describes the evolution of our understanding of the biological role played by synthetic and natural antimicrobial cationic peptides and by the highly basic nuclear histones as modulators of infection, postinfectious sequelae, trauma, and coagulation phenomena. The authors discuss the effects of the synthetic polymers of basic poly α amino acids, poly l-lysine, and poly l-arginine on blood coagulation, fibrinolysis, bacterial killing, and blood vessels; the properties of natural and synthetic antimicrobial cationic peptides as potential replacements or adjuncts to antibiotics; polycations as opsonizing agents promoting endocytosis/phagocytosis; polycations and muramidases as activators of autolytic wall enzymes in bacteria, causing bacteriolysis and tissue damage; and polycations and nuclear histones as potential virulence factors and as markers of sepsis, septic shock, disseminated intravasclar coagulopathy, acute lung injury, pancreatitis, trauma, and other additional clinical disorders

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Penicillin-binding protein inactivation by human neutrophil myeloperoxidase.

Cited by 12 publications

References 27 publications

The role of bacteriolysis in the pathophysiology of inflammation, infection and post‐infectious sequelae

The role of bacteriolysis in the pathophysiology of inflammation, infection and post‐infectious sequelae

Oxidation of intracellular glutathione after exposure of human red blood cells to hypochlorous acid

From amino acids polymers, antimicrobial peptides, and histones, to their possible role in the pathogenesis of septic shock: a historical perspective

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