Bacterial pore-forming toxins

Ulhuq, Fatima R.; Mariano, Giuseppina

doi:10.1099/mic.0.001154

Cited by 27 publications

(29 citation statements)

References 249 publications

(537 reference statements)

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“…The fundamental step of pore formation consists of binding of toxin protomers to a receptor (lipids, glycans or proteins) on the surface of the target cell membrane. Receptors increase the local concentration of the toxin and also promote oligomerization [ 76 ]. As was also demonstrated previously, flavonoids could interact with phospholipid and protein components of erythrocyte membranes and protect erythrocytes against hypotonic lysis [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity of Quercetin, Naringenin and Catechin: Flavonoids Inhibit Staphylococcus aureus-Induced Hemolysis and Modify Membranes of Bacteria and Erythrocytes

et al. 2023

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Search for novel antimicrobial agents, including plant-derived flavonoids, and evaluation of the mechanisms of their antibacterial activities are pivotal objectives. The goal of this study was to compare the antihemolytic activity of flavonoids, quercetin, naringenin and catechin against sheep erythrocyte lysis induced by α-hemolysin (αHL) produced by the Staphylococcus aureus strain NCTC 5655. We also sought to investigate the membrane-modifying action of the flavonoids. Lipophilic quercetin, but not naringenin or catechin, effectively inhibited the hemolytic activity of αHL at concentrations (IC50 = 65 ± 5 µM) below minimal inhibitory concentration values for S. aureus growth. Quercetin increased the registered bacterial cell diameter, enhanced the fluidity of the inner and surface regions of bacterial cell membranes and raised the rigidity of the hydrophobic region and the fluidity of the surface region of erythrocyte membranes. Our findings provide evidence that the antibacterial activities of the flavonoids resulted from a disorder in the structural organization of bacterial cell membranes, and the antihemolytic effect of quercetin was related to the effect of the flavonoid on the organization of the erythrocyte membrane, which, in turn, increases the resistance of the target cells (erythrocytes) to αHL and inhibits αHL-induced osmotic hemolysis due to prevention of toxin incorporation into the target membrane. We confirmed that cell membrane disorder could be one of the direct modes of antibacterial action of the flavonoids.

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Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity of Quercetin, Naringenin and Catechin: Flavonoids Inhibit Staphylococcus aureus-Induced Hemolysis and Modify Membranes of Bacteria and Erythrocytes

et al. 2023

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“…Time‐resolved studies of VapA binding and intercalation using a biosensor and film balance revealed a significant decrease in membrane fluidity and limited intercalation of VapA. To spatially visualize the interaction positions of VapA on model membranes and to determine whether VapA, like other bacterial pore formers, organizes into oligomeric structures on or in the membrane (Ulhuq & Mariano, 2022; Yamashita et al., 2014), we use atomic force microscopy (AFM), which allows imaging of surfaces in air and in liquid with nanometer spatial resolution. First, solid‐supported monolayers were prepared by single Langmuir–Blodgett transfer and examined by AFM.…”

Section: Resultsmentioning

confidence: 99%

The mechanistic basis of the membrane‐permeabilizing activities of the virulence‐associated protein A (VapA) from Rhodococcus equi

Nehls,

Schröder,

Haubenthal

et al. 2024

Molecular Microbiology

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Pathogenic Rhodococcus equi release the virulence‐associated protein A (VapA) within macrophage phagosomes. VapA permeabilizes phagosome and lysosome membranes and reduces acidification of both compartments. Using biophysical techniques, we found that VapA interacts with model membranes in four steps: (i) binding, change of mechanical properties, (ii) formation of specific membrane domains, (iii) permeabilization within the domains, and (iv) pH‐specific transformation of domains. Biosensor data revealed that VapA binds to membranes in one step at pH 6.5 and in two steps at pH 4.5 and decreases membrane fluidity. The integration of VapA into lipid monolayers was only significant at lateral pressures <20 mN m−1 indicating preferential incorporation into membrane regions with reduced integrity. Atomic force microscopy of lipid mono‐ and bilayers showed that VapA increased the surface heterogeneity of liquid disordered domains. Furthermore, VapA led to the formation of a new microstructured domain type and, at pH 4.5, to the formation of 5 nm high domains. VapA binding, its integration and lipid domain formation depended on lipid composition, pH, protein concentration and lateral membrane pressure. VapA‐mediated permeabilization is clearly distinct from that caused by classical microbial pore formers and is a key contribution to the multiplication of Rhodococcus equi in phagosomes.

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“…4d ), suggesting potential molecular differences between mechanisms of T6SS induction by polymyxin B versus by PSMs treatment. Polymyxin B can be inserted into the membrane, causing cell lysis by creating pores in the envelope 34 . In contrast, PSMs are cationic, amphipathic small helical peptides with membrane perturbing and cell surface-adhering properties 35 .…”

Section: Resultsmentioning

confidence: 99%

Staphylococcalsecreted cytotoxins are competition sensing signals forPseudomonas aeruginosa

Wang

Warren

Haas

et al. 2023

Preprint

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Coinfection with two notorious opportunistic pathogens, the Gram-negativePseudomonas aeruginosaand Gram-positiveStaphylococcus aureus, dominates chronic pulmonary infections. While coinfection is associated with poor patient outcomes, the interspecies interactions responsible for such decline remain unknown. Here, we dissected molecular mechanisms of interspecies sensing betweenP. aeruginosaandS. aureus. We discovered thatP. aeruginosasensesS. aureussecreted peptides and, counterintuitively, moves towards these toxins.P. aeruginosatolerates such a strategy through competition sensing, whereby it preempts imminent danger/competition by arming cells with type six secretion (T6S) and iron acquisition systems. Intriguingly, while T6S is predominantly described as weaponry targeting Gram-negative and eukaryotic cells, we find that T6S is essential for fullP. aeruginosacompetition withS. aureus, a previously undescribed role for T6S. Importantly, competition sensing was activated during coinfection of bronchial epithelia, including T6S islands targeting human cells. This study reveals critical insight into both interspecies competition and how antagonism may cause collateral damage to the host environment.

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Bacterial pore-forming toxins

Cited by 27 publications

References 249 publications

Antimicrobial Activity of Quercetin, Naringenin and Catechin: Flavonoids Inhibit Staphylococcus aureus-Induced Hemolysis and Modify Membranes of Bacteria and Erythrocytes

Antimicrobial Activity of Quercetin, Naringenin and Catechin: Flavonoids Inhibit Staphylococcus aureus-Induced Hemolysis and Modify Membranes of Bacteria and Erythrocytes

The mechanistic basis of the membrane‐permeabilizing activities of the virulence‐associated protein A (VapA) from Rhodococcus equi

Staphylococcalsecreted cytotoxins are competition sensing signals forPseudomonas aeruginosa

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