Control of cytoskeletal dynamics during cellular responses to pore forming toxins

Mesquita, Francisco; Brito, Cláudia; Cabanes, Didier; Sousa, Sandra

doi:10.1080/19420889.2017.1349582

Cited by 11 publications

(19 citation statements)

References 40 publications

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“…Furthermore, NM IIA might have multiple roles in the reaction of intracellular L. monocytogenes infection. For instance, Mesquita et al (2017) found that listeriolysin O (LLO) induces the reorganization of the NM II A network into cortical bundles for the formation of plasma membrane blebs, whereas NM IIA protects plasma membrane integrity against LLO intoxication during L . monocytogenes infection (Mesquita et al, 2017).…”

Section: Nm II In Microbial-triggered Discordsmentioning

confidence: 99%

Non-muscle Myosin II: Role in Microbial Infection and Its Potential as a Therapeutic Target

et al. 2019

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Currently, the major measures of preventing and controlling microbial infection are vaccinations and drugs. However, the appearance of drug resistance microbial mounts is main obstacle in current anti-microbial therapy. One of the most ubiquitous actin-binding proteins, non-muscle myosin II (NM II) plays a crucial role in a wide range of cellular physiological activities in mammals, including cell adhesion, migration, and division. Nowadays, growing evidence indicates that aberrant expression or activity of NM II can be detected in many diseases caused by microbes, including viruses and bacteria. Furthermore, an important role for NM II in the infection of some microbes is verified. Importantly, modulating the expression of NM II with small hairpin RNA (shRNA) or the activity of it by inhibitors can affect microbial-triggered phenotypes. Therefore, NM II holds the promise to be a potential target for inhibiting the infection of microbes and even treating microbial-triggered discords. In spite of these, a comprehensive view on the functions of NM II in microbial infection and the regulators which have an impact on the roles of NM II in this context, is still lacking. In this review, we summarize our current knowledge on the roles of NM II in microbial-triggered discords and provide broad insights into its regulators. In addition, the existing challenge of investigating the multiple roles of NM II in microbial infection and developing NM II inhibitors for treating these microbial-triggered discords, are also discussed.

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Section: Nm II In Microbial-triggered Discordsmentioning

confidence: 99%

Non-muscle Myosin II: Role in Microbial Infection and Its Potential as a Therapeutic Target

et al. 2019

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“…Interestingly, calcium chelators inhibit blebbing [ 145 ], suggesting that calcium is required for NM2 contraction and subsequent bleb formation and retraction. Indeed, blebbing is triggered by a variety of calcium-dependent mechanisms known to activate NM2 and/or induce cytoskeleton rearrangements such as plasma membrane repair upon bacterial-induced pore formation [ 146 , 162 , 163 , 164 , 165 , 166 ].…”

Section: Nm2a In Membrane Blebbingmentioning

confidence: 99%

“…Infection studies demonstrated that pathogens such as Kaposi’s sarcoma-associated herpesvirus and Listeria monocytogenes target NM2A, inducing its phosphorylation, which is detrimental for cellular invasion [ 75 , 211 ]. Listeriolysin O (LLO), a pore-forming toxin produced by L. monocytogenes , induces the redistribution and remodeling of NM2A into cortical bundles that promote plasma membrane (PM) repair after LLO-induced PM disruption [ 162 , 163 ]. This mechanism is shared by other pore-forming toxins, such as PFO that is expressed by Clostridium perfringens [ 166 ], suggesting a protective role for NM2A during infection by bacterial pathogens.…”

Section: Nm2a In Diseasementioning

confidence: 99%

Non-Muscle Myosin 2A (NM2A): Structure, Regulation and Function

Brito

Sousa

2020

Cells

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Non-muscle myosin 2A (NM2A) is a motor cytoskeletal enzyme with crucial importance from the early stages of development until adulthood. Due to its capacity to convert chemical energy into force, NM2A powers the contraction of the actomyosin cytoskeleton, required for proper cell division, adhesion and migration, among other cellular functions. Although NM2A has been extensively studied, new findings revealed that a lot remains to be discovered concerning its spatiotemporal regulation in the intracellular environment. In recent years, new functions were attributed to NM2A and its activity was associated to a plethora of illnesses, including neurological disorders and infectious diseases. Here, we provide a concise overview on the current knowledge regarding the structure, the function and the regulation of NM2A. In addition, we recapitulate NM2A-associated diseases and discuss its potential as a therapeutic target.

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“…Resealing of the membrane pore through regulation of membrane lipids, control of cytoskeletal dynamics, enhancement of blebbing and microvesicle shedding are some of the attractive options for further investigation [128,129,130,131]. For example, the decrease in cytoplasmic potassium after pore formation promotes inflammasome activation through caspase-1, leading to maturation of the important pro-immune and pro-inflammatory cytokine IL-1β to combat infection.…”

Section: Increasing Host Cell Resiliency Against Pore-forming Toximentioning

confidence: 99%

Pharmacological Targeting of Pore-Forming Toxins as Adjunctive Therapy for Invasive Bacterial Infection

Escajadillo

Nizet

2018

Toxins

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For many of the most important human bacterial infections, invasive disease severity is fueled by the cell damaging and pro-inflammatory effects of secreted pore-forming toxins (PFTs). Isogenic PFT-knockout mutants, e.g., Staphylococcus aureus lacking α-toxin or Streptococcus pneumoniae deficient in pneumolysin, show attenuation in animal infection models. This knowledge has inspired multi-model investigations of strategies to neutralize PFTs or counteract their toxicity as a novel pharmacological approach to ameliorate disease pathogenesis in clinical disease. Promising examples of small molecule, antibody or nanotherapeutic drug candidates that directly bind and neutralize PFTs, block their oligomerization or membrane receptor interactions, plug establishment membrane pores, or boost host cell resiliency to withstand PFT action have emerged. The present review highlights these new concepts, with a special focus on β-PFTs produced by leading invasive human Gram-positive bacterial pathogens. Such anti-virulence therapies could be applied as an adjunctive therapy to antibiotic-sensitive and -resistant strains alike, and further could be free of deleterious effects that deplete the normal microflora.

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Control of cytoskeletal dynamics during cellular responses to pore forming toxins

Cited by 11 publications

References 40 publications

Non-muscle Myosin II: Role in Microbial Infection and Its Potential as a Therapeutic Target

Non-muscle Myosin II: Role in Microbial Infection and Its Potential as a Therapeutic Target

Non-Muscle Myosin 2A (NM2A): Structure, Regulation and Function

Pharmacological Targeting of Pore-Forming Toxins as Adjunctive Therapy for Invasive Bacterial Infection

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