Staphylococcus aureus alpha toxin can bind to cholesterol-sensitive phosphatidyl choline head group arrangements

Thurnheer, Sarah; Abrami, Laurence; Bischofberger, Mirko; Goot, F. Gisou van der

doi:10.19185/matters.201602000024

“…It is known, the interaction of αHL with membranes occurs at the level of the phosphatidylcholine head group 69,70 and/or the ADAM10 protein receptor in the case of red blood cell highly sensitive to the toxin, such as rabbit erythrocytes 54 .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of interaction between Staphylococcus aureus α-hemolysin and erythrocytes membrane by hydrolysable tannins: structure-related activity study

Olchowik-Grabarek

¹

,

Sękowski

²

,

Bitiucki

³

et al. 2020

Sci Rep

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The objective of the study was a comparative analysis of the antihemolytic activity against two Staphylococcus aureus strains (8325-4 and NCTC 5655) as well as α-hemolysin and of the membrane modifying action of four hydrolysable tannins with different molecular mass and flexibility: 3,6-bis-O-di-O-galloyl-1,2,4-triO -galloyl-β-d-glucose (T1), 1,2,3,4,5-penta-O-galloyl-β-d-glucose (T2), 3-O-galloyl-1,2-valoneoyl-β-d-glucose (T3) and 1,2-di-O-galloyl-4,6-valoneoyl-β-d-glucose (T4). We showed that all the compounds studied manifested antihemolytic effects in the range of 5-50 µM concentrations. However, the degree of the reduction of hemolysis by the investigated tannins was not uniform. A valoneoyl group-containing compounds (T3 and T4) were less active. Inhibition of the hemolysis induced by α-hemolysin was also noticed on preincubated with the tannins and subsequently washed erythrocytes. In this case the efficiency again depended on the tannin structure and could be represented by the following order: T1 > T2 > T4 > T3. We also found a relationship between the degree of antihemolytic activity of the tannins studied and their capacity to increase the ordering parameter of the erythrocyte membrane outer layer and to change zeta potential. Overall, our study showed a potential of the T1 and T2 tannins as anti-virulence agents. The results of this study using tannins with different combinations of molecular mass and flexibility shed additional light on the role of tannin structure in activity manifestation. Over the past few years, a significant increase in bacterial resistance to antibiotics and transference of resistance genes from animal to human strains has become a global medical problem. Therefore, constant search for new antimicrobial agents among them being compounds of plant origin, including polyphenols, is ongoing 1,2. In addition to the antibiotic approaches of combating bacteria, anti-virulence strategies have also been considered recently. An anti-virulent strategy assumes a direct effect of compounds on virulent factors by reducing

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“…Of the other CAP pathogens, Staphylococcus aureus , albeit a relatively uncommon cause of CAP, produces a pore-forming cytolysin, α-hemolysin. This bacterial toxin initiates lethal membrane damage via a complex mechanism following interaction with sphingomyelin/cholesterol [ 65 ], which has been implicated in the pathogenesis of coronary dysfunction in a murine model of experimental cardiotoxicity [ 66 ].…”

Section: Role Of Pneumolysin In Cardiac Dysfunction During Severe Pne...mentioning

confidence: 99%

The Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy

Feldman

¹

2023

IJMS

1

0

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Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.

show abstract

The Global Burden of Community-Acquired Pneumonia, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, With a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy

Feldman¹

2023

Preprint

1

0

View full text Add to dashboard Cite

Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.

show abstract

Staphylococcus aureus alpha toxin can bind to cholesterol-sensitive phosphatidyl choline head group arrangements

Cited by 4 publications

References 11 publications

Inhibition of interaction between Staphylococcus aureus α-hemolysin and erythrocytes membrane by hydrolysable tannins: structure-related activity study

Inhibition of interaction between Staphylococcus aureus α-hemolysin and erythrocytes membrane by hydrolysable tannins: structure-related activity study

The Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy

The Global Burden of Community-Acquired Pneumonia, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, With a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy

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