scholarly journals Octominin: A Novel Synthetic Anticandidal Peptide Derived from Defense Protein of Octopus minor

Marine Drugs ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 56 ◽  
Author(s):  
Chamilani Nikapitiya ◽  
S.H.S. Dananjaya ◽  
H.P.S.U. Chandrarathna ◽  
Mahanama De Zoysa ◽  
Ilson Whang
Keyword(s):  
Cell Wall ◽  
Cell Membrane ◽  
Antimicrobial Agents ◽  
Membrane Integrity ◽  
Alpha Helix ◽  
Infection Model ◽  
Dependent Manner ◽  
Cell Membrane Integrity ◽  
Defense Protein ◽  
Octopus Minor

The rapid emergence of multidrug-resistant pathogens makes an urgent need for discovering novel antimicrobial agents as alternatives to conventional antibiotics. Towards this end, we designed and synthesized a synthetic peptide of 23 amino acids (AAs) (1GWLIRGAIHAGKAIHGLIHRRRH23) from a defense protein 3 cDNA sequence of Octopus minor. The sequence of the peptide, which was named Octominin, had characteristic features of known antimicrobial peptides (AMPs) such as a positive charge (+5), high hydrophobic residue ratio (43%), and 1.86 kcal/mol of Boman index. Octominin was predicted to have an alpha-helix secondary structure. The synthesized Octominin was 2625.2 Da with 92.5% purity. The peptide showed a minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of 50 and 200 μg/mL, respectively, against Candida albicans. Field emission scanning electron microscopy observation confirmed that Octominin caused ultrastructural cell wall deformities in C. albicans. In addition, propidium iodide penetrated the Octominin-treated C. albicans cells, further demonstrating loss of cell membrane integrity that caused cell death at both MIC and MFC. Octominin treatment increased the production of intracellular reactive oxygen species and decreased cell viability in a concentration dependent manner. Cytotoxicity assays revealed no significant influence of Octominin on the viability of human embryonic kidney 293T cell line, with over 95% live cells in the Octominin-treated group observed up to 100 µg/mL. Moreover, we confirmed the antifungal action of Octominin in vivo using a zebrafish experimental infection model. Overall, our results demonstrate the Octominin is a lead compound for further studies, which exerts its effects by inducing cell wall damage, causing loss of cell membrane integrity, and elevating oxidative stress.

scholarly journals Antimicrobial Peptide AMP-17 Affects Candida albicans by Disrupting Its Cell Wall and Cell Membrane Integrity

2020 ◽  
Vol Volume 13 ◽  
pp. 2509-2520
Author(s):  
Huiling Ma ◽  
Xinyu Zhao ◽  
Longbing Yang ◽  
Peipei Su ◽  
Ping Fu ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Cell Membrane ◽  
Antimicrobial Peptide ◽  
Membrane Integrity ◽  
Cell Membrane Integrity

scholarly journals Molecular Toxicological Mechanisms of Synthetic Cathinones on C2C12 Myoblasts

2019 ◽  
Vol 20 (7) ◽  
pp. 1561 ◽  
Author(s):  
Xun Zhou ◽  
Dino Luethi ◽  
Gerda Sanvee ◽  
Jamal Bouitbir ◽  
Matthias Liechti ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Membrane ◽  
Complex I ◽  
Membrane Integrity ◽  
Synthetic Cathinones ◽  
Cellular Respiration ◽  
Dependent Manner ◽  
C2c12 Myoblasts ◽  
Cell Membrane Integrity ◽  
Mitochondrial Superoxide

Synthetic cathinones are popular psychoactive substances that may cause skeletal muscle damage. In addition to indirect sympathomimetic myotoxicity, these substances could be directly myotoxic. Since studies in myocytes are currently lacking, the aim of the present study was to investigate potential toxicological effects by synthetic cathinones on C2C12 myoblasts (mouse skeletal muscle cell line). We exposed C2C12 myoblasts to 3-methylmethcathinone, 4-methylmethcathinone (mephedrone), 3,4-methylenedioxymethcathinone (methylone), 3,4-methylenedioxypyrovalerone (MDPV), alpha-pyrrolidinovalerophenone (α-PVP), and naphthylpyrovalerone (naphyrone) for 1 or 24 h before cell membrane integrity, ATP content, mitochondrial oxygen consumption, and mitochondrial superoxide production was measured. 3,4-Methylenedioxymethamphetamine (MDMA) was included as a reference compound. All investigated synthetic cathinones, as well as MDMA, impaired cell membrane integrity, depleted ATP levels, and increased mitochondrial superoxide concentrations in a concentration-dependent manner in the range of 50–2000 μM. The two pyrovalerone derivatives α-PVP and naphyrone, and MDMA, additionally impaired basal and maximal cellular respiration, suggesting mitochondrial dysfunction. Alpha-PVP inhibited complex I, naphyrone complex II, and MDMA complex I and III, whereas complex IV was not affected. We conclude that, in addition to sympathetic nervous system effects and strenuous muscle exercise, direct effects of some cathinones on skeletal muscle mitochondria may contribute to myotoxicity in susceptible synthetic cathinone drugs users.

scholarly journals Altering the Proclivity towards Daptomycin Resistance in Methicillin-Resistant Staphylococcus aureus Using Combinations with Other Antibiotics

2012 ◽  
Vol 56 (10) ◽  
pp. 5046-5053 ◽  
Author(s):  
Andrew D. Berti ◽  
Justine E. Wergin ◽  
Gary G. Girdaukas ◽  
Scott J. Hetzel ◽  
George Sakoulas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Membrane ◽  
Membrane Integrity ◽  
Wall Thickening ◽  
Methicillin Resistant ◽  
Content Type ◽  
Cell Membrane Integrity ◽  
Cell Membrane Fluidity

ABSTRACTDaptomycin (DAP) is increasingly used as a part of combination therapy, particularly in complex methicillin-resistantStaphylococcus aureus(MRSA) infections. While multiple studies have reported the potential for synergy between DAP and adjunctive anti-infectives, few have examined the influence of adjunctive therapy on the emergence of DAP resistance. This study examined eight adjunctive antimicrobial combinations with DAPin vitroand the emergence of DAP resistance over time (up to 4 weeks) using clinical isolates of DAP-susceptible MRSA (MIC, 0.5 μg/ml) in which DAP resistance subsequently developed during patient therapy (MIC, 3 μg/ml). In addition to DAP susceptibility testing, selected strains were examined for phenotypic changes associated with DAP resistance, including changes to cell wall thickness (CWT) and cell membrane alterations. The addition of either oxacillin or clarithromycin in medium containing DAP significantly inhibited the development of DAP resistance through the entirety of the 4-week exposure (10- to 32-fold MIC reduction from that of DAP alone). Combinations with rifampin or fosfomycin were effective in delaying the emergence of DAP resistance through the end of week one only (week one MIC, 0.5 μg/ml; week four MIC, 24 μg/ml). Cell wall thickening was observed for all antibiotic combinations regardless of their effect on the DAP MIC (14 to 70% increase in CWT), while changes in cell membrane fluidity were variable and treatment dependent. DAP showed reduced activity against strains with DAP MICs of 1 to 12 μg/ml, but cell membrane integrity was still disrupted at concentrations achieved with doses greater than 10 mg/kg of body weight. The emergence of DAP resistance in MRSA is strongly influenced by the presence of subinhibitory concentrations of adjunctive antimicrobials. These data suggest that combining DAP with oxacillin or clarithromycin may delay the development of DAP resistance in cases requiring prolonged antibiotic therapy.

scholarly journals New Functionalized Macroparticles for Environmentally Sustainable Biofilm Control in Water Systems

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 399
Author(s):  
Ana C. Barros ◽  
Ana Pereira ◽  
Luis F. Melo ◽  
Juliana P. S. Sousa
Keyword(s):  
Cell Membrane ◽  
Antimicrobial Agents ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Membrane System ◽  
Bacterial Cells ◽  
Cell Membrane Integrity ◽  
Cell Membrane Damage ◽  
Environmentally Sustainable ◽  
Partial Blocking

Reverse osmosis (RO) depends on biocidal agents to control the operating costs associated to biofouling, although this implies the discharge of undesired chemicals into the aquatic environment. Therefore, a system providing pre-treated water free of biocides arises as an interesting solution to minimize the discharge of chemicals while enhancing RO filtration performance by inactivating bacteria that could form biofilms on the membrane system. This work proposes a pretreatment approach based on the immobilization of an industrially used antimicrobial agent (benzalkonium chloride—BAC) into millimetric aluminum oxide particles with prior surface activation with DA—dopamine. The antimicrobial efficacy of the functionalized particles was assessed against Escherichia coli planktonic cells through culturability and cell membrane integrity analysis. The results showed total inactivation of bacterial cells within five min for the highest particle concentration and 100% of cell membrane damage after 15 min for all concentrations. When reusing the same particles, a higher contact time was needed to reach the total inactivation, possibly due to partial blocking of immobilized biocide by dead bacteria adhering to the particles and to the residual leaching of biocide. The overall results support the use of Al2O3-DA-BAC particles as antimicrobial agents for sustainable biocidal applications in continuous water treatment systems.

Quercetin in attenuation of ischemic/reperfusion injury: A review

2020 ◽  
Vol 13 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Saeed Samarghandian ◽  
Kiavash Hushmandi ◽  
Amirhossein Zabolian ◽  
Md Shahinozzaman ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Blood Supply ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Membrane Integrity ◽  
Therapeutic Effects ◽  
Molecular Pathways ◽  
Cell Membrane Integrity ◽  
Cell Membrane Disruption

Background: Ischemia/reperfusion (I/R) injury is a serious pathologic event that occurs due to restriction in blood supply to an organ, followed by hypoxia. This condition leads to enhanced levels of pro-inflammatory cytokines such as IL-6 and TNF-, and stimulation of oxidative stress via enhancing reactive oxygen species (ROS) levels. Upon reperfusion, blood supply increases, but it deteriorates condition, and leads to generation of ROS, cell membrane disruption and finally, cell death. Plant derived-natural compounds are well-known due to their excellent antioxidant and anti-inflammatory activities. Quercetin is a flavonoid exclusively found in different vegetables, herbs, and fruits. This naturally occurring compound possesses different pharmacological activities making it appropriate option in disease therapy. Quercetin can also demonstrate therapeutic effects via affecting molecular pathways such as NF-B, PI3K/Akt and so on. Methods: In the present review, we demonstrate that quercetin administration is beneficial in ameliorating I/R injury via reducing ROS levels, inhibition of inflammation, and affecting molecular pathways such as TLR4/NF-B, MAPK and so on. Results and conclusion: Quercetin can improve cell membrane integrity via decreasing lipid peroxidation. Apoptotic cell death is inhibited by quercetin via down-regulation of Bax, and caspases, and upregulation of Bcl-2. Quercetin is able to modulate autophagy (inhibition/induction) in decreasing I/R injury. Nanoparticles have been applied for delivery of quercetin, enhancing its bioavailability and efficacy in alleviation of I/R injury. Noteworthy, clinical trials have also confirmed the capability of quercetin in reducing I/R injury.

scholarly journals The importance of extracellular speciation and corrosion of copper nanoparticles on lung cell membrane integrity

2016 ◽  
Vol 141 ◽  
pp. 291-300 ◽  
Author(s):  
Jonas Hedberg ◽  
Hanna L. Karlsson ◽  
Yolanda Hedberg ◽  
Eva Blomberg ◽  
Inger Odnevall Wallinder
Keyword(s):  
Cell Membrane ◽  
Copper Nanoparticles ◽  
Membrane Integrity ◽  
Cell Membrane Integrity
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