Pore-Forming Toxins During Bacterial Infection: Molecular Mechanisms and Potential Therapeutic Targets

Hu, Hai‐Jie; Liu, Min; Sun, Shuang

doi:10.2147/dddt.s322393

Cited by 8 publications

(5 citation statements)

References 84 publications

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“…Hemolysins are important virulence factors in pathogenic infections since they induce RBC lysis and release of iron, which is an essential nutrient requirement for pathogens. Iron is an important element for life since it is required for making important enzymes in all living cells[ 36 , 59 , 61 , 62 ]. However, iron is never found in a free form in biological tissues or in the extracellular fluids; the ability of most pathogens to survive in an iron-free environment highly depends on its iron acquisition talents including hemolysin and siderophore production[ 63 ].…”

Section: Bacterial Virulence Factors and Their Contribution To Pathog...mentioning

confidence: 99%

What’s old is new again: Insights into diabetic foot microbiome

Rajab¹,

Hegazy²

2023

World J Diabetes

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Diabetes is a chronic disease that is considered one of the most stubborn global health problems that continues to defy the efforts of scientists and physicians. The prevalence of diabetes in the global population continues to grow to alarming levels year after year, causing an increase in the incidence of diabetes complications and health care costs all over the world. One major complication of diabetes is the high susceptibility to infections especially in the lower limbs due to the immunocompromised state of diabetic patients, which is considered a definitive factor in all cases. Diabetic foot infections continue to be one of the most common infections in diabetic patients that are associated with a high risk of serious complications such as bone infection, limb amputations, and life-threatening systemic infections. In this review, we discussed the circumstances associated with the high risk of infection in diabetic patients as well as some of the most commonly isolated pathogens from diabetic foot infections and the related virulence behavior. In addition, we shed light on the different treatment strategies that aim at eradicating the infection.

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Section: Bacterial Virulence Factors and Their Contribution To Pathog...mentioning

confidence: 99%

What’s old is new again: Insights into diabetic foot microbiome

Rajab¹,

Hegazy²

2023

World J Diabetes

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“…LukAB and γ-haemolysin were both reported to target the NLRP3 inflammasome in monocytes and macrophages, by a mechanism that has yet to be fully elucidated. The current model suggests that K + efflux causes NLRP3 inflammasome activation and a pro-inflammatory response, which leads to pyroptosis in a caspase-dependent manner [23, 96, 98]. Similarly, VCC was found to promote apoptosis in a caspase-dependent manner and vacuole formation in different human cell lines [99].…”

Section: Pore Forming Toxins As Virulence Factorsmentioning

confidence: 99%

“…Many PFTs represent virulence factors and play multifaceted roles in pathogen infection, by directly or indirectly contributing to pathogen invasion and dissemination [22,23]. Pore insertion into the eukaryotic plasma membrane causes uncontrolled efflux of nutrients and ions, especially K + , and can also perturb Ca 2+ signalling.…”

Section: Pore Forming Toxins As Virulence Factorsmentioning

confidence: 99%

Bacterial pore-forming toxins

Ulhuq

Mariano

2022

Microbiology

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Pore-forming toxins (PFTs) are widely distributed in both Gram-negative and Gram-positive bacteria. PFTs can act as virulence factors that bacteria utilise in dissemination and host colonisation or, alternatively, they can be employed to compete with rival microbes in polymicrobial niches. PFTs transition from a soluble form to become membrane-embedded by undergoing large conformational changes. Once inserted, they perforate the membrane, causing uncontrolled efflux of ions and/or nutrients and dissipating the protonmotive force (PMF). In some instances, target cells intoxicated by PFTs display additional effects as part of the cellular response to pore formation. Significant progress has been made in the mechanistic description of pore formation for the different PFTs families, but in several cases a complete understanding of pore structure remains lacking. PFTs have evolved recognition mechanisms to bind specific receptors that define their host tropism, although this can be remarkably diverse even within the same family. Here we summarise the salient features of PFTs and highlight where additional research is necessary to fully understand the mechanism of pore formation by members of this diverse group of protein toxins.

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“…One of the key factors of bacterial pathogenicity is hemolytic toxin II (hemolysin II, HlyII), which belongs to the group of β-pore-forming toxins [3,4]. This toxin is secreted by bacteria in the form of water-soluble monomers and oligomerizes in the presence of the plasma membrane of the target cell to form transmembrane pores, leading to a disruption of osmotic pressure inside the cell and ultimately to its destruction, providing bacteria with access to nutrients [5,6]. HlyII of B. cereus is capable of lysing erythrocytes [5] and other eukaryotic cells [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Utilizing Extraepitopic Amino Acid Substitutions to Define Changes in the Accessibility of Conformational Epitopes of the Bacillus cereus HlyII C-Terminal Domain

Rudenko,

Nagel,

Melnik

et al. 2023

IJMS

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Hemolysin II (HlyII)—one of the pathogenic factors of Bacillus cereus, a pore-forming β-barrel toxin—possesses a C-terminal extension of 94 amino acid residues, designated as the C-terminal domain of HlyII (HlyIICTD), which plays an important role in the functioning of the toxin. Our previous work described a monoclonal antibody (HlyIIC-20), capable of strain-specific inhibition of hemolysis caused by HlyII, and demonstrated the dependence of the efficiency of hemolysis on the presence of proline at position 324 in HlyII outside the conformational antigenic determinant. In this work, we studied 16 mutant forms of HlyIICTD. Each of the mutations, obtained via multiple site-directed mutagenesis leading to the replacement of amino acid residues lying on the surface of the 3D structure of HlyIICTD, led to a decrease in the interaction of HlyIIC-20 with the mutant form of the protein. Changes in epitope structure confirm the high conformational mobility of HlyIICTD required for the functioning of HlyII. Comparison of the effect of the introduced mutations on the effectiveness of interactions between HlyIICTD and HlyIIC-20 and a control antibody recognizing a non-overlapping epitope enabled the identification of the amino acid residues N339 and K340, included in the conformational antigenic determinant recognized by HlyIIC-20.

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Pore-Forming Toxins During Bacterial Infection: Molecular Mechanisms and Potential Therapeutic Targets

Cited by 8 publications

References 84 publications

What’s old is new again: Insights into diabetic foot microbiome

What’s old is new again: Insights into diabetic foot microbiome

Bacterial pore-forming toxins

Utilizing Extraepitopic Amino Acid Substitutions to Define Changes in the Accessibility of Conformational Epitopes of the Bacillus cereus HlyII C-Terminal Domain

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