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Bacitracin and Gramicidin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Recent surveys of bacterial resistance to gramicidin are not available, but development of resistance is still thought to be very low despite its wide use in over-the-counter products. One of the postulated explanations for this is that gramicidin targets multiple crucial pathways in the cell (Marr et al., 2006). Resistance of S. aureus to gramicidin S has been reported (Orlova et al., 2003).
Electron Spin Resonance Spectroscopy
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
George C. Yang, Adorjan Aszalos
The interaction of antibiotics plymixin B, gramicidin S, and chlorothricin was initially studied by Packe et al. [40,41] using artificial and bacterial membranes. In the ESR experiments, the fluidity of egg yolk lecithin and the phospholipids of Bacillus subtilis was investigated in the presence and absence of chlorothricin with two spin probes, 12-nitroxylmethylstearate and distearoylglycerophosphate, derivatized on the phosphate with tetramethyl-3-hydroxymethylpyrrolidin-l-oxyl. The rotational correlation times (τc) obtained with different mole percent chlorothricin and the 12-nitroxylmethylstearate probe were calculated. Results indicated that increasing the concentration of the antibiotic increases the rigidity (immobilization) of inner areas of the membrane. However, using the distearoylglycerophosphate spin label, very few changes in the rotational freedom and correlation time were observed with increasing amounts of antibiotic added to the membrane preparation. The 12-nitroxylmethylstearate probe inserts deep into the membrane and senses fluidity changes; the phospholipid spin probe resides near the membrane surface and senses no fluidity change. It could be concluded that chlorothricin also penetrates deep inside the membrane near the position where the 12-nitroxylmethylstearate probe resides. In contrast to chlorothricin, polymixin B and gramicidin S remain at the outside of membranes. Experimentally, the addition of these two antibiotics to egg yolk lecithin does not alter position of the 12-nitroxylmethylstearate. The mode of action of various antibiotics may depend on their depth of membrane penetration. This can be determined by ESR spectroscopy with different spin probes.
Mitochondria in Huntington’s Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
MitoC, a mitochondria-targeted version of the hydrophilic antioxidant ascorbate, can be taken up by mitochondria and reacts with a range of reactive species. Because of its accumulation and recycling, MitoC is an effective antioxidant against mitochondrial lipid peroxidation and decreases aconitase inactivation by superoxide (Finichiu et al., 2015). Mitochondrially targeted glutathione or glutathione inducers preferentially enter mitochondria where they neutralize free radicals, decrease oxidative damage, and protect neurons against protein oxidation, loss of mitochondrial function, and DNA fragmentation induced by Aβ (Pocernich et al., 2001; Boyd-Kimball et al., 2005a, 2005b). Mitochondria-targeted curcumin (MTC) exerted neuroprotective effects against rotenone-induced oxidative damage in the cerebellum of mice, and MTC is more effective than curcumin alone (Hasan et al., 2020). The transgenic MitoPark mice that are selective knockout of Tfam in dopaminergic neurons recapitulate many signature features of PD, including progressive motor deficits, neuronal loss, and protein inclusions. Mito-apocynin showed excellent central nervous system bioavailability, significantly improved locomotor activity and coordination in MitoPark mice, and partially attenuated severe nigrostriatal degeneration in MitoPark mice. Mechanistic studies revealed that Mito-apocynin improves mitochondrial function and inhibits NOX2 activation, oxidative damage, and neuroinflammation (Langley et al., 2017). Neuronal mitochondria-targeted micelles (CT-NM) were prepared through codecoration with neural cell adhesion molecule mimetic peptide C3 for brain neuron-specific binding and the triphenylphosphonium for mitochondrial targeting (Yang et al., 2020). CT-NM significantly increased the encapsulated resveratrol’s concentration in the neuronal mitochondria compared to the micelles modified with C3 only or the resveratrol solution. The resveratrol-loaded CT-NM alleviated the oxidative stress in the neuronal cells, resulting in the stabilization of the dynamic balance of mitochondrial fission and fusion. The targeted micelles restored the cognitive performance in APP/PS1 transgenic mice by upregulation of sirtuin 1 expression, reduction of amyloid deposition and tau hyperphosphorylation, protection of synapses, and inhibition of microglial proliferation (Yang et al., 2020). Another mitochondrial-targeted antioxidant is called XJB-5-131 which is a bifunctional antioxidant comprising a radical scavenger, 4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl nitroxide, conjugated to a mitochondrial targeting moiety (Xun et al., 2012). The targeting portion of the molecule is an alkene peptide isostere modification of the Leu-D-Phe-Pro-Val-Orn segment of the antibiotic gramicidin S (Hoye et al., 2008; Wipf et al., 2005) that localizes to the mitochondrial membrane. XJB-5-131 reduces oxidative damage to mitochondrial DNA, maintains mitochondrial DNA copy number, suppresses motor decline and weight loss, enhances neuronal survival, and improves mitochondrial function in a knock-in model of HD, as well as shows beneficial effects in R6/2 HD mice (Xun et al., 2012; Polyzos et al., 2016, 2018).
Gramicidin inhibits cholangiocarcinoma cell growth by suppressing EGR4
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Xiaoli Gong, Liming Zou, Miaomiao Wang, Yingheng Zhang, Shuxian Peng, Mingtian Zhong, Jiankui Zhou, Xun Li, Xiaodong Ma
Gramicidin are a class of polypeptide substances, which are extracted from the culture of bacillus brevis and the family members include gramicidin A, gramicidin B, gramicidin C, gramicidin D and gramicidin S [8,9]. The gramicidin A is the best characterised channel forming ionophore and two monomers dimerise to form a functional nanopore within the lipid bilayer [10]. The formation of gramicidin A channel renders biological membranes permeable to specific cations which disrupts cellular ionic homeostasis and then changes the permeability of cells, so that cells can not normally carry out metabolic activities and be inhibited or even died [11]. For quite a long time, the research on gramicidin A is more about making full use of its cationic channel characteristics as a carrier of related substances or modifying it to make it a better intramembrane transport. Recently in renal cell carcinoma, gramicidin A was found to block tumour growth and tumour cell metabolic dysfunction [10,12,13]. However, use of gramicidin A as an antitumor agent has not been widely evaluated on other solid tumours.
The purification and functional study of new compounds produced by Escherichia coli that influence the growth of sulfate reducing bacteria
Published in Egyptian Journal of Basic and Applied Sciences, 2020
Oluwafemi Adebayo Oyewole, Julian Mitchell, Sarah Thresh, Vitaly Zinkevich
Several studies have described some inhibitors of SRB growth that are derived from bacteria; for example, Jayaraman et al. [69] and Zuo [29] reported that indolicidin, bactenecin, and polymyxin produced by Paenibacillus polymyxa are capable of inhibiting SRB growth. Bacillus brevis produces a compound referred to as gramicidin-S that inhibits the growth of Desulfovibrio orientis, D. vulgaris and D. gigas [29,31,70] and thereby reduced corrosion caused by the SRB. In addition, Bacillus licheniformis secretes γ-polyglutamate and polyaspartate that reduce SRB growth [29,71,72]. The mechanism of SRB growth prevention by these organisms has been suggested and include either the production of antimicrobial agents [29,73] or attack on the adenosine 5ʹ- phosphosulphate (APS) and bisulfate reductase (DSR) responsible for hydrogen sulfide production in SRBs [14]. Similarly, the SGE may function in SRB induction by increasing their growth rate while the SGI may function by causing damage in the cells as observed in this study. The MALDI-TOF spectra showed the presence of low molecular weight compounds in the range of 1700 Da for SGE and 2400 Da for SGI. The spectra showed equal and repeating units of ~213 m/z between the peaks. According to Wallace and Guttman [74], the equal and repeating units are characteristic spectra of condensation homopolymers. MALDI-TOF spectra revealed that the compounds are small molecular weight biomolecules and that the two molecules are very closely related.
Developments with investigating descriptors for antimicrobial AApeptides and their derivatives
Published in Expert Opinion on Drug Discovery, 2018
Olapeju Bolarinwa, Jianfeng Cai
Motivated by the antimicrobial activity of linear γ-AApeptides, we investigated the effects of cyclization on their antimicrobial activity. Macrocyclic peptide antibiotics including gramicidin S, protegrin I, tyrocidine, and Polymyxin B are products of nature [36]. These class of peptide antibiotics generally possess semi-rigid backbones that favor the proper positioning of substituents due to reduced rotational freedom.