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Role of Nanoparticles in Cancer Immunotherapy
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Liposome-based nanocarriers have shown immense potential for delivering peptides to APCs. pH-sensitive liposomes are one of the good choices as they will be released into the cytosol by destabilizing or fusing with lysosomal membrane. Hyper-branched polyglycidol derivative liposomes confer escape from lysosomal degradation [69]. Adding adjuvant (pharmacological or immunological agent that improves the immune response of a vaccine) also along with antigen shows enhanced immune responses. Miyabe et al. have reported YSK05, a synthetic pH-sensitive liposome with optimal functionality at pH 6.5, as a suitable carrier (c-di-GMP/YSK05 liposomes) for cytosol transport of a cyclic dinucleotide cyclic-di-GMP (an adjuvant) to stimulate innate immune responses via STING-TBK1-IRF3 pathway [70]. However, despite several advantages, liposomes are not very suitable as they release the antigens quickly. Poly(lactic-co-glycolic acid) (PLGA) has advantage over liposome, as it has sustained release of antigens resulting in enhanced immune responses compared to fast release liposome [71]. Not only PLGA, but poly(propylene) sulfide (PPS) NPs and GNPs as well show better antigen delivery to APCs [72, 73]. GNPs show low cytotoxicity, easily controllable size and shape, and designer surface chemistry, which make them a good choice for antigen delivery.
Microbial Biofilms
Published in Chaminda Jayampath Seneviratne, Microbial Biofilms, 2017
Chaminda Jayampath Seneviratne, Neha Srivastava, Intekhab Islam, Kelvin Foong and Finbarr Allen
Dispersal is the least understood and perhaps the most complicated process in both fungal and bacterial biofilm development. The trigger for the dispersal process to occur and the biological pathways modulating dispersal may vary considerably among different microorganisms [41]. Cells from the biofilm may detach singly or as a group and move through a fluid phase to seed new sites. Numerous research groups have put forth efforts to understand this mechanism in pathogenic organisms such as P. aeruginosa and C. albicans. Bacterial secondary messengers such as cyclic di-GMP have been shown to provide critical signals for biofilm formation as well as dispersal [42]. The factors which signal dispersion can vary, ranging from environmental stimuli, nutrients, certain chemicals such as cis-2-decenoic acid or nitric oxide or proteins such as BdlA, a chemotaxis regulator [43–45]. It has also been shown recently that phosphorylation status of diguanylate cyclase NIcD can affect the dispersal of biofilms in P. aeruginosa [46]. The aforementioned study demonstrated dispersal inducing environmental cues are sensed by the diguanylate cyclase NicD belonging to a seven transmembrane receptor family. The sensing of dispersal cues by NicD results in NicD dephosphorylation, followed by activation of a chemotaxis regulator BdlA, which in turn activates DipA, a phosphodiesterase molecule. This leads to altered levels of second messenger cyclic-di-GMP molecules signalling dispersion. Studies on C. albicans biofilms have found Set3–NRG1 complex as possible regulators of biofilm dispersal. Set3, an NAD-dependent histone deacetylation complex, modulates NRG, a transcriptional regulator of biofilm dispersal and a repressor of filamentation [47]. The typical dispersal of C. albicans from biofilms is in the yeast form [48]. Moreover, it was shown that deletion of Nrg1 gene in C. albicans attenuates in vivo virulence of the fungus in systemic candidiasis [49]. Therefore, with proper understanding of the dispersal process, alternative therapeutic strategies may be devised for controlling the spread of these pathogenic organisms.
Bacterial biofilm-derived antigens: a new strategy for vaccine development against infectious diseases
Published in Expert Review of Vaccines, 2021
Abraham Loera-Muro, Alma Guerrero-Barrera, Yannick Tremblay D.N., Skander Hathroubi, Carlos Angulo
Some signaling molecules can be used by bacteria for intra-species and inter-species communications. One of these molecules is the second messenger, cyclic di-GMP (c-di-GMP). In bacteria, c-di-GMP promotes the switch between lifestyles: a sedentary biofilm or a motile free-floating lifestyle [52]. It also affects a wide range of bacterial behaviors, including the cell cycle, motility, fimbrial synthesis, type III secretion, modulation of RNA, stress response, bacterial predation, and virulence [53]. Diguanylate cyclases have a GGDEF domain that generates c-di-GMP from two GTP molecules, whereas phosphodiesterases have a EAL or HD-GYP domain that degrades c-di-GMP to pGpG [54]. Specific c-di-GMP receptor proteins or riboswitch RNAs sense the changes in c-di-GMP levels and regulate specific processes resulting in different phenotypes [53]. Higher diguanylate cyclase activity increases intracellular c-di-GMP levels that stimulate the production of various adhesins and biofilm-associated matrix components resulting in increased adhesion and biofilm formation [52]. On the opposite spectrum, high phosphodiesterase activity reduces the levels of c-di-GMP, which suppresses adhesion leading to biofilm dispersion [54]. For example, Legionella pneumophila, an opportunistic pathogen, uses the second messenger c-di-GMP to regulate an array of bacterial processes that include motility, cell division, differentiation, virulence, as well as biofilm formation [55,56].
In situ characterisation of biofilms formed by psychrotrophic meat spoilage pseudomonads
Published in Biofouling, 2019
Nirmani N. Wickramasinghe, Joshua T. Ravensdale, Ranil Coorey, Gary A. Dykes, P. Scott Chandry
A large number of planktonic bacteria were visible moving among cellular aggregates during the early stages of biofilm formation. Planktonic bacteria were not observed in 7-day old biofilms grown at 4 °C or after day 3 of 10 °C grown biofilms. Biofilm grown after these time temperature combinations are more mature and mature biofilms do not contain many planktonic cells (Valentini and Filloux 2016). A key characteristic that is common to the biofilm mode of life is the high concentration of cyclic di-GMP (c-di-GMP), a secondary messenger which has been demonstrated to supresses flagella mediated swimming motility and promotes matrix production (Merighi et al. 2008; Diane et al. 2011). Mature biofilms contained high concentration of c-di-GMP. The absence of planktonic cells in the mature biofilms may be attributed to the activity of cyclic-di-GMP. Further studies measuring cyclic-di-GMP levels are necessary to study this hypothesis for meat biofilms formed by P. fragi and P. lundensis.
Quorum sensing pathways in Gram-positive and -negative bacteria: potential of their interruption in abating drug resistance
Published in Journal of Chemotherapy, 2019
Shafiul Haque, Dinesh K. Yadav, Shekhar C. Bisht, Neelam Yadav, Vineeta Singh, Kashyap Kumar Dubey, Arshad Jawed, Mohd Wahid, Sajad Ahmad Dar
Remarkable ability of bacteria to evolve mechanisms that render bacteriocidal/bacteriostatic antibiotics ineffective has led to re-evaluation of new antibiotics to manage bacterial infections. Efforts to explore novel QS-interfering compounds have intensified since the first report of QS interference in D. pulchra.227 Antagonitic QS compounds disrupting signal molecule synthesis, inhibiting their diffusion, blocking their binding to cognate receptors and preventing the signal transduction, are able to reduce the selection pressure. Broad reviews identified with QS have advanced our understanding of bacterial signalling pathways that prompt the formation of virulence factors and biofilms in bacteria. Identification and biochemical characterization of several receptors for the universal QS molecule, like AI-2, is foreseen. Moreover, the structure of AI-3 is to be unraveled and more information regarding the structure of Lux-R type receptors is also expected. Besides, the RNA molecules and adaptor proteins that tie to cyclic-di-GMP and transfer signals for expression of virulence factors or biofilm development are probably going to be recognized and characterized. Present review demonstrates that interface amongst QS and bacterial virulence is a promising area with potential to drive the emergence of new and effective anti-virulence drugs, and that inhibiting bacterial virulence by QS inhibition is favourable and applicable.