Autophagy in Staphylococcus aureus Infection

Wang, Mengyao; Fan, Ziyao; Han, Hongbing

doi:10.3389/fcimb.2021.750222

Cited by 20 publications

(24 citation statements)

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“…The intracellular survival mechanism of S. aureus contributes to pathogen dissemination among organ tissues, resulting in disease progression or recurrence (Löffler et al, 2014 ; Horn et al, 2018 ; Wang et al, 2021 ) and even being at a chronic situation. Plectasin, NZ2114, and MP1102 can kill intracellular S. aureus in human THP-1 macrophages and RAW 264.7 cells, respectively (Brinch et al, 2009 , 2010 ; Wang et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…One of the major causes of recurrent peritonitis is from the emergence of antibacterial resistance during antibiotic treatment, especially from methicillin-resistant and multiple resistant strains (Li et al, 2020a ; Camargo et al, 2021 ). In addition, S. aureus can invade and replicate in various host cells, complicating the usage of antibiotics (Zhou et al, 2018 ; Wang et al, 2021 ); therapeutic effects were impeded by poor penetration or inferior intracellular stability. Therefore, there is an urgent need to develop new intracellular antibacterial drugs with low resistance and high cellular permeability for the treatment or prevention of S. aureus -related peritonitis diseases.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics and Pharmacodynamics of Fungal Defensin NZX Against Staphylococcus aureus-Induced Mouse Peritonitis Model

et al. 2022

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Staphylococcus aureus (S. aureus) is one of the most common pathogenic bacteria responsible for causing a life-threatening peritonitis disease. NZX, as a variant of fungal defensin plectasin, displayed potent antibacterial activity against S. aureus. In this study, the antibacterial and resistance characteristics, pharmacokinetics, and pharmacodynamics of NZX against the S. aureus E48 and S. aureus E48-induced mouse peritonitis model were studied, respectively. NZX exhibited a more rapid killing activity to S. aureus (minimal inhibitory concentration, 1 μg/ml) compared with linezolid, ampicillin and daptomycin, and serial passaging of S. aureus E48 for 30 days at 1/2 × MIC, NZX had a lower risk of resistance compared with ampicillin and daptomycin. Also, it displayed a high biocompatibility and tolerance to physiological salt, serum environment, and phagolysosome proteinase environment, except for acid environment in phagolysosome. The murine serum protein-binding rate of NZX was 89.25% measured by ultrafiltration method. Based on the free NZX concentration in serum after tail vein administration, the main pharmacokinetic parameters for T1/2, Cmax, Vd, MRT, and AUC ranged from 0.32 to 0.45 h, 2.85 to 20.55 μg/ml, 1469.10 to 2073.90 ml/kg, 0.32 to 0.56 h, and 1.11 to 8.89 μg.h/ml, respectively. Additionally, the in vivo pharmacodynamics against S. aureus demonstrated that NZX administrated two times by tail vein at 20 mg/kg could rescue all infected mice in the lethal mouse peritonitis model. And NZX treatment (20 mg/kg) significantly reduced CFU counts in the liver, lung, and spleen, especially for intracellular bacteria in the peritoneal fluid, which were similar or superior to those of daptomycin. In vivo efficacies of NZX against total bacteria and intracellular bacteria were significantly correlated with three PK/PD indices of ƒAUC/MIC, ƒCmax/MIC, and ƒT% > MIC analyzed by a sigmoid maximum-effect model. These results showed that NZX may be a potential candidate for treating peritonitis disease caused by intracellular S. aureus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Fungal Defensin NZX Against Staphylococcus aureus-Induced Mouse Peritonitis Model

et al. 2022

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“…S. aureus is recruited to the autophagosome membrane by early phagosomes bearing Rab5 and Rab22b to LC3 labeled by Rab7 and LAMP-1 in the presence of Hla. S. aureus can inhibit the fusion of autophagosomes with lysosomes to form autolysosomes and thus replicate within the autophagosome without being killed [ 264 , 265 ]. However, S. aureus can inhibit autophagosome maturation and fusion with lysosomes, escape from autophagosomes into the cytoplasm, and lead to host cell death, which does not rely on caspase [ 266 ].…”

Section: Types Of Host Cell Death Caused By S Aureusmentioning

confidence: 99%

Exploring the Role of Staphylococcus aureus in Inflammatory Diseases

Chen

Zhang

et al. 2022

Toxins

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Staphylococcus aureus is a very common Gram-positive bacterium, and S. aureus infections play an extremely important role in a variety of diseases. This paper describes the types of virulence factors involved, the inflammatory cells activated, the process of host cell death, and the associated diseases caused by S. aureus. S. aureus can secrete a variety of enterotoxins and other toxins to trigger inflammatory responses and activate inflammatory cells, such as keratinocytes, helper T cells, innate lymphoid cells, macrophages, dendritic cells, mast cells, neutrophils, eosinophils, and basophils. Activated inflammatory cells can express various cytokines and induce an inflammatory response. S. aureus can also induce host cell death through pyroptosis, apoptosis, necroptosis, autophagy, etc. This article discusses S. aureus and MRSA (methicillin-resistant S. aureus) in atopic dermatitis, psoriasis, pulmonary cystic fibrosis, allergic asthma, food poisoning, sarcoidosis, multiple sclerosis, and osteomyelitis. Summarizing the pathogenic mechanism of Staphylococcus aureus provides a basis for the targeted treatment of Staphylococcus aureus infection.

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“…Consequently, it has been observed that genetic mutations affecting autophagic genes promote cellular degeneration [ 103 , 104 ], promote early-age-related phenotypes [ 105 , 106 ], tumor development [ 107 , 108 ], and susceptibility to infections in animals [ 109 , 110 ]. Similarly, mutations of genes related to autophagy are present in several Mendelian diseases in humans such as Rett’s syndrome, Parkinson’s disease, cataracts, several forms of cardiomyopathies, among others [ 111 ].…”

Section: Autophagy and Animal Healthmentioning

confidence: 99%

Antimicrobial peptides with cell-penetrating activity as prophylactic and treatment drugs

2022

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Health is fundamental for the development of individuals and evolution of species. In that sense, for human societies is relevant to understand how the human body has developed molecular strategies to maintain health. In the present review, we summarize diverse evidence that support the role of peptides in this endeavor. Of particular interest to this review are antimicrobial (AMP) and cell-penetrating peptides (CPP). Different experimental evidence indicates that AMP/CPP are able to regulate autophagy, which in turn regulates the immune system response. AMP also assists in the establishment of the microbiota, which in turn is critical for different behavioral and health aspects of humans. Thus, AMP and CPP are multifunctional peptides that regulate two aspects of our bodies that are fundamental to our health: autophagy and microbiota. While it is now clear the multifunctional nature of these peptides, we are still in the early stages of the development of computational strategies aimed to assist experimentalists in identifying selective multifunctional AMP/CPP to control non-healthy conditions. For instance, both AMP and CPP are computationally characterized as amphipatic and cationic, yet none of these features are relevant to differentiate these peptides from non-AMP or non-CPP. This review aims to highlight current knowledge that may facilitate the development of AMP’s design tools for preventing or treating illness.

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Autophagy in Staphylococcus aureus Infection

Cited by 20 publications

References 72 publications

Pharmacokinetics and Pharmacodynamics of Fungal Defensin NZX Against Staphylococcus aureus-Induced Mouse Peritonitis Model

Pharmacokinetics and Pharmacodynamics of Fungal Defensin NZX Against Staphylococcus aureus-Induced Mouse Peritonitis Model

Exploring the Role of Staphylococcus aureus in Inflammatory Diseases

Antimicrobial peptides with cell-penetrating activity as prophylactic and treatment drugs

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