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A Biophysical View on the Function and Activity of Endotoxins
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Ulrich Seydel, Andre Wiese, Andra B. Schromm, Klaus Brandenburg
A detailed characterization of the various functions of the bacterial outer membrane is complicated by its complexity. Therefore, the reconstitution of simpler model systems (e.g., as a first step that of the unmodified lipid matrix being composed on one side of LPS and on the other side of phospholipids) is a feasible approach to studying the role of single amphiphilic components of the outer membrane, in particular that of LPS. This refers in the first place to the role of LPS in its potential interaction with membrane-active substances like drugs, detergents, and components of the immune system. The influence of LPS on the function of transmembrane proteins may, in subsequent steps, be studied by reconstitution of the proteins into the bilayer.
Genetically Modified Salmonella as Cancer Therapeutics: Mechanisms, Advances, and Challenges
Published in Ananda M. Chakrabarty, Arsénio M. Fialho, Microbial Infections and Cancer Therapy, 2019
The display of proteins on bacteria is an attractive way to enhance bacterial tumor targeting efficiency and present heterologous proteins to the host immune system. The heterologous genes were fused into the gene encoding bacterial outer membrane proteins OmpA [92–94]. In addition, LamB and flagellin can be utilized to present heterologous proteins or peptides on the bacterial outer membrane. Anticarcinoembryonic antigen (scFV), anti-CD20 peptide, and RGD peptide were reported to be displayed on attenuated Salmonella and resulted in increased tumor targeting efficiency and therapeutic effects. Anti-CD20 antibody was displayed on attenuated Salmonella delivering a prodrug-converting enzyme to treat human lymphoma [94]. Park et al. showed that the display of the RGD peptide sequence on the outer membrane of Salmonella resulted in increased tumor targeting efficiency and therapeutic effects [93]. It has been assumed that the display of heterologous antigen has the potential to elicit potent humoral immunity. However, no successful evidence or example has been reported yet.
Beneficial Lactic Acid Bacteria
Published in K. Balamurugan, U. Prithika, Pocket Guide to Bacterial Infections, 2019
Pathogenic microorganisms can cause adverse effects on the body, leading to death ultimately. LAB helps to prevent proliferation and growth of pathogens. One of the mechanisms of antimicrobial activity is produced by secretion of bioactive compounds. Some chemicals, like bacteriocins demonstrate activity toward specific group, species, or strain of bacteria. Eliminating pathogenic bacteria, the broad-spectrum bacteriocins may change microbiota diversity (Rea et al. 2011). Short-chain fatty acids (SCFA), like lactic acid, affect bacterial fitness via acid stress, additionally modulating host immune functions and serving as metabolic substrates (Sun and O’Riordan 2013). Lactic acid, besides pH reduction, also functions as a permeabilizer of the gram-negative bacterial outer membrane and may act as a potentiator of the effects of other antimicrobial substances (Alakomi et al. 2000). Hydrogen peroxide shows microbicidal properties by damaging cell structure. Some studies demonstrated that hydrogen peroxide displayed enhanced killing activity in the presence of lactic acid, while in other cases pathogens could be suppressed with acid but not peroxide (Atassi and Servin 2010; O’Hanlon et al. 2011).
Differential transformation and antibacterial effects of silver nanoparticles in aerobic and anaerobic environment
Published in Nanotoxicology, 2019
P. aeruginosa can produce EPS forming a capsule wrapping the cell (Ma et al. 2009; Mann and Wozniak 2012), which act as the outer defense layer against environmental stress. EPS contain diverse functional groups and have excellent metal-binding property (Kang, Alvarez, & Zhu 2014). It has reported that bacterial EPS and biofilm are able to reduce Ag+ and Au+ to metal nanoparticles (Kang, Alvarez, and Zhu 2014; Kang et al. 2017; Reith et al. 2006). We did observe nanoparticles embedded in EPS matrix (Figures 3(b-i) & 4(a,b)). Silver ions can diffuse further into the cells. The lipopolysaccharides and proteins in bacterial outer membrane are rich in thiol, carboxyl, aldehyde and amino residuals that have strong capability to bind Ag+ (Eckhardt et al. 2013). The bacterial cells might attract Ag+ and accumulate AgNPs to form clusters. The AgNP formation mechanism includes aggregative growth that small nanocrystals with the same crystallographic orientation combine together to form nanoparticles (Wang, Richards, et al. 2014; Woehl et al. 2013). Silver ions might be reduced at the cluster’s interface. The AgNP clusters merged into large particles.
Peptidoglycan-associated lipoprotein of Aggregatibacter actinomycetemcomitans induces apoptosis and production of proinflammatory cytokines via TLR2 in murine macrophages RAW 264.7 in vitro
Published in Journal of Oral Microbiology, 2018
Riikka Ihalin, Kjell Eneslätt, Sirkka Asikainen
The role of LPS in infections caused by Gram-negative bacteria has been widely studied (for review, see ref [9].). However, current interest concerning Gram-negative infections is increasingly focused on bacterial outer membrane proteins (OMPs), especially lipoproteins [10]. In fact, recent studies have suggested that bacterial lipoproteins are major players in inflammatory reactions caused by pathogenic species, such as Shigella flexneri, Brucella abortus, and Salmonella enterica [11–13]. Regarding A. actinomycetemcomitans, 23 different lipoproteins are detectable among the proteins secreted by A. actinomyctemcomitans biofilm [14], but their bioactivity is poorly understood [15–17]. More knowledge is available for other AaOMPs (e.g. a 100-kDa OMP), which promotes adherence and invasion to human cells, and induction of IL-1b and TNF-a production by mouse macrophages [18]. Furthermore, a 29-kDa AaOMP is involved in bacterial internalization in gingival epithelial cells [17], and the 12-kDa OapB most likely inhibits the host defence enzyme lysozyme [14,19].
Novel pyochelin-based PEGylated liposomes for enhanced delivery of antibiotics against resistant clinical isolates of Pseudomonas aeruginosa
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Pradeep Pushparaj Selvadoss, Jayshree Nellore, Malathy Balaraman Ravindrran, Uma Sekar
Siderophore-mediated iron transport is an important strategy employed by P. aeruginosa to acquire iron from the surrounding environment. This pathway facilitates the possibility of delivering anti-pseudomonal drugs across the bacterial outer membrane. Many considerable kinds of literature focusing siderophore antibiotic conjugates are available for their therapeutic purposes [33–35] and in particular, Rivault et al. [36] demonstrated the conjugation of norfloxacin to the terminal amine group of pyochelin analogs for delivering antibiotics to P. aeruginosa. Therefore, iron acquisition systems have become important targets for novel drug design. PEGylated liposomes with the siderophore, pyochelin, were chosen to eradicate MDRPa as described in Scheme 3.