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Lactic Acid Bacteria Bacteriocins and their Impact on Human Health
Published in Marcela Albuquerque Cavalcanti de Albuquerque, Alejandra de Moreno de LeBlanc, Jean Guy LeBlanc, Raquel Bedani, Lactic Acid Bacteria, 2020
Svetoslav D Todorov, Michael L Chikindas
Recently, Naimi et al. (2018) evaluated stability and bacteriocin activity of microcin J25 produced by E. coli in TIM-1 model, simulating human GIT conditions. Microcin J25 is the bacteriocin active against Salmonella, Shigella, and pathogenic E. coli strains. Microcin J25 is a 21 amino acid peptide, with remarkable stability to heat and extreme pH values. It is also resistant to several proteases, resistance related to bacteriocins specific lasso structure (Naimi et al. 2018). Authors have used LC-MS/MS analysis and subsequent molecular networking analysis on the Global Natural Products Social Molecular Networking platform (GNPS), and analysis of the peptide degradation in the presence of proteolytic enzymes mimicking the GIT conditions with the aim to delineate the fate of microcin J25 through identification of the main degradation products. Microcin J25 was relatively stable under studied gastric conditions, but degraded rapidly in the compartment mimicking the duodenum, notably in the presence of pancreatin. Based on Naimi et al. (2018), among pancreatin components, elastase I appeared primarily responsible for microcin J25 breakdown while α-chymotrypsin was less effective. Authors have provided detailed analysis of the breakdown of microcin J25 in different parts of the GIT and predicted levels of activity during the passage through the GIT.
Bacteria and Bioactive Peptides
Published in Prakash Srinivasan Timiri Shanmugam, Understanding Cancer Therapies, 2018
Ameer Khusro, Chirom Aarti, Paul Agastian
Microcins are small sized (<10 kDa) bacteriocins secreted by Enterobacteria (mostly E. coli) under conditions of nutrient depletion. To date, 14 microcins have been reported, out of which only seven have been isolated and characterized. The toxicity of microcin E492 has been demonstrated against various human malignant cell lines such as HeLa (human cervical adenocarcinoma), Jurkat (T-cell derived from acute T-cell leukemia), RJ2.25 (a variant of Burkitt's lymphoma), and colorectal carcinoma cells. The peptide showed no effect against normal bone marrow cells, splenocytes, KG-1, and nontumor macrophage-derived cells (Hetz et al. 2002). It was also observed that M-E492 caused apoptosis and necrosis at lower and higher concentrations, respectively, showing cell shrinkage, DNA fragmentation and extracellular exposure of phosphatidylserine, loss of mitochondrial membrane potential, and release of calcium ions from intracellular stores (Hetz et al. 2002). The in vivo effects of M-E492 on human tumor cells were studied in a preclinical model using mice, showing that M-E492 fibrils administered had anticancer activity (Lagos et al. 2009).
Prospective Therapeutic Applications of Bacteriocins as Anticancer Agents
Published in Ananda M. Chakrabarty, Arsénio M. Fialho, Microbial Infections and Cancer Therapy, 2019
Lígia F. Coelho, Nuno Bernardes, Arsénio M. Fialho
Microcins are produced by Enterobacteriaceae, and just like colicins they are secreted under conditions of lack of nutrients compelling antibacterial activity against closely related species. Microcin E492 (Table 10.1), expressed by Klebsiella pneumoniae RYC492, was suggested in 2002 by Hetz et al., to exert toxicity against solid and hematological malignant cell lines, such as human cervix adenocarcinoma, T cell leukemia, lymphoma, and colorectal carcinoma cell [29]. The effects appeared to be typical of apoptosis in HeLa cells, although in higher concentrations microcin caused necrosis. Indeed, regulatory apoptosis proteins, such as the Bcl-2 family, are controlled by mitochondrial permeability. ACPs that are able to enter malignant cells and cause membrane pores in the mitochondria trigger the release of its components and liberate Bcl-2. Usually, the recently released cytochrome c forms a complex with caspase-9, initiating a cascade of signals related to apoptosis intrinsic pathway, leading to cell death [17, 70, 71]. In situations where the plasmatic and/or mitochondrial membrane is too disrupted, the necrosis mechanism is triggered. Dual-action ACPs are very valuable, given the fact that apoptosis is a preferred mode of cell death in comparison with necrosis because it is not known to induce an inflammatory response. Also, in this study other effects, including cell shrinkage, DNA fragmentation, and extracellular exposure of PS, were observed in cancer cells treated with microcin E492. Finally, microcin did not appear to be cytotoxic against nonmalignant bone marrow cells and mice [29, 72]. Lastly, there is also registration of antitumoral activity of microcin E492 fibrils administered in a human colorectal carcinoma xenograft in nude mice [30].
Non-antibiotic antibacterial peptides and proteins of Escherichia coli: efficacy and potency of bacteriocins
Published in Expert Review of Anti-infective Therapy, 2021
Juraj Bosák, Matěj Hrala, Lenka Micenková, David Šmajs
To date, over 30 different bacteriocin types have been characterized as products of E. coli and related bacteria; having different spectra of antibacterial activities. Several microcin types have already been found to be promising molecules for medical applications and for food preservation, being active against important human foodborne infectious agents, such as pathogenic E. coli and Salmonella isolates. Several colicin types show a relatively broad spectrum of activity on E. coli isolates and are, therefore, suitable for treatment of infections caused by uropathogenic, enterohaemorrhagic, and shiga- and enterotoxigenic E. coli strains, while activity of some other colicins is specific for a particular group of pathogenic bacteria, e.g. colicin JS and Z were shown to have a specific effect on enteroinvasive E. coli and Shigella strains.
Microbiota modulation-based therapy for luminal GI disorders: current applications of probiotics and fecal microbiota transplantation
Published in Expert Opinion on Biological Therapy, 2019
Abbinaya Elangovan, Jessica R. Allegretti, Monika Fischer
AAD is defined as an otherwise unexplained diarrhea that occurs in conjunction with antibiotic administration [12]. Antibiotics such as clindamycin are shown to dramatically decrease the beneficial gram-positive anaerobes such as Clostridia, Lactobacilli, and Bifidobacteria leading to a considerable imbalance in the intestinal flora [13]. Probiotics could be useful in AAD through a variety of mechanisms. They enhance the barrier function through production of mucin, microcin, and bacteriocin (proteins with anti-bacterial properties). They further inhibit microbes through competitive adherence of intra-luminal binding sites and restriction of microbial passage across the intestinal epithelium [14].
Gut microbiota as a source of novel antimicrobials
Published in Gut Microbes, 2019
Enriqueta Garcia-Gutierrez, Melinda J. Mayer, Paul D. Cotter, Arjan Narbad
Bacteriocins can control and protect from specific infections. Microcins have recently proved their ability to act as narrow-spectrum antimicrobials to limit the proliferation of Enterobacteriaceae during intestinal inflammation by giving E. coli Nissle 1917, a probiotic originally isolated from the human gut, a competitive advantage.145 This is the first evidence of the ecological role that microcins might play in the gut and opens a door to further therapeutical applications.