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Nodulin Function and Nodulin Gene Regulation in Root Nodule Development
Published in Peter M. Gresshoff, Molecular Biology of Symbiotic Nitrogen Fixation, 2018
DNA sequence analysis of the partial cDNA clone pGmENOD245 and the corresponding complete genomic sequence49 revealed that proline is the major amino acid of the Ngm-75 nodulin. The amino acid sequence is organized in highly repetitive units, composed of 17 times the pentapeptide repeat Pro-Pro-His-Glu-Lys, 6 times this repeat with only a single amino acid substitution, in addition to 13 times the repeat Pro-Pro-Glu-Tyr/His-Gln (Figure 2). These repeats are found at the core of the amino acid sequence. At the amino and carboxy terminal ends, the pentapeptide repetitive structure is maintained, although individual amino acids deviate, A putative signal peptide is present at the amino terminal sequence,49,50 suggesting that the Ngm-75 protein is transported across a membrane. As no proline-rich proteins have been described in plants, and as soybean nodule tissue is known to be extremely hydroxyproline rich,51 it seems likely that the prolines become hydroxylated in vivo to yield a hydroxyproline-rich protein.
Finafloxacin
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
Full resistance to finafloxacin and other fluoroquinolones can occur from mutation in the GyrA subunit of DNA gyrase and ParC subunit of topoisomerase IV, with an increasing number of these mutations associated with higher levels of resistance (Emrich et al., 2009; Leow et al., 2008). Mutations tend to cluster in certain regions (termed the quinolone resistance-determing region [QRDR]) of GyrA or ParC. For finafloxacin in E. coli, a QRDR Ser83Leu mutation in GyrA causes an 8- to 16-fold increase in MIC; a similar increase is also seen with a comparable mutation in P. aeruginosa (Goh et al., 2010b). For E. coli, additional mutations in either GyrA or ParC can cause a further increase in MIC of 8- to 128-fold. In S. aureus (\Dalhoff et al., 2011) and in clinical isolates of A. baumannii (Higgins et al., 2010) there are progressive increases in MIC associated with the presence of mutations in GyrA and in GyrA together with ParC. Clinical isolates of H. pylori with GyrA mutations also had overall higher MICs than those without such mutations (Lee et al., 2015). Resistance can also occur by mutations in genes that regulate the expression of endogenous bacterial efflux pumps that can actively remove some quinolones from the cell. For finafloxacin in E. coli, marR mutations, which cause both increased expression of the AcrAB-TolC efflux pump and decreases in outer membrane diffusion channel OmpF, can cause an eightfold increase in MIC (Emrich et al., 2009). In P. aeruginosa, regulatory mutations that cause an increased expression of the MexAB-OprM and MexEF-OprN efflux pumps cause increases in finafloxacin MIC of eight- and fourfold, respectively. Increased expression of the MexCD-OpM pump, however, appears not to affect susceptibility to finafloxacin (Goh et al., 2010b). As noted above, plasmids that confer low-level quinolone resistance have also been found in enteric Gram-negative bacteria. Those plasmid-encoded genes that reduce susceptibility to finafloxacin include qnrA (16-fold), qnrB (32-fold), and qnrS (eightfold), which encode proteins of the pentapeptide repeat family that protect gyrase from quinolone action (Emrich et al., 2010; Robicsek et al., 2006a). Two other plasmid-encoded resistance determinants, qepA, which encodes an efflux pump affecting susceptibility to a broad range of quinolones (Périchon et al., 2007; Yamane et al., 2007), and aac(6ʹ)-Ib-cr, which encodes a variant of an aminoglycoside-modifying acetyl transferase enzyme that can modify some quinolones such as ciprofloxacin (Robicsek et al., 2006b), do not reduce the activity of finafloxacin (Emrich et al., 2010).
Current advances in cell therapeutics: a biomacromolecules application perspective
Published in Expert Opinion on Drug Delivery, 2022
Samson A. Adeyemi, Yahya E. Choonara
Elastin is a bio-synthetic biomacromolecule synthesized from human elastin sequences as the backbone[105]. Elastin-Like Polypeptides (ELPs) are produced from a plasmid-borne gene in Escherichia coli [106] which are then extracted by purifying the cell lysates and characterized by large monomers with repeating units. Based on this bio-engineering technique Rodriguez-Cabello and co-workers [107] coined the term elastin-like ‘recombinamer’ (ELR). The VPGVG pentapeptide repeat is a widely investigated ELR family and represents the most ubiquitous sequence found in human elastin naturally. Several other ELRs have been manufactured from the VPGVG repeat by replacing the fourth amino acid with other naturally occurring amino acids, except proline. When heated, ELRs respond to heat and show a reversible sol-gel transition interphase. At transition temperature, they form a random-coil conformation and when heated, the chain folds hydrophobically to form a uniform b-spiral stabilized structure. The polymer molecular weight, its concentration in solution and composition of the amino acids control the transition temperature and can be monitored to stabilize between room and body temperature. In addition, it is possible to engineer this biomacromolecule to accommodate biodegradation sequences [108] or add specific cell adhesion motifs [109]. For instance, Costa and co-workers [110,111] added chitosan as a polycation to a negatively charged ELR having the RGD motifs to synthesize microcapsules using a layer-by-layer technique for application in the transport of bioactive agents and cells in tissue engineering.
Mechanisms of antimicrobial resistance in Stenotrophomonas maltophilia: a review of current knowledge
Published in Expert Review of Anti-infective Therapy, 2020
Teresa Gil-Gil, José Luis Martínez, Paula Blanco
The chromosomally encoded qnr gene confers low-level resistance to quinolones [64]. This gene codes for a pentapeptide repeat protein that protects the DNA topoisomerases from the action of fluoroquinolones [65]. It has been reported that there is large variability within Smqnr alleles in clinical isolates, each allele presenting subtle differences in its contibution to S. maltophilia quinolone resistance [65–68]. Smqnr expression is regulated by SmqnrR, although this regulation seems to be strain-specific [69].
Therapeutic nanocarriers comprising extracellular matrix-inspired peptides and polysaccharides
Published in Expert Opinion on Drug Delivery, 2021
Lucas C. Dunshee, Millicent O. Sullivan, Kristi L. Kiick
Some of the earliest ELPs studied were crosslinked synthetic polymers of the common tropoelastin residue repeat motifs such as poly(VPGVG) [24], which were produced to better understand the thermodynamics of the self-assembly/coacervation phenomena of tropoelastin, and also evaluate tropoelastin’s structure [24]. With the advent of modern molecular biology techniques, specific sequences of ELPs with precise chain lengths could be easily synthesized with well-defined chemical and thermodynamic properties [25]. These recombinant ELPs typically comprise a generalized pentapeptide repeat (VPGXAAG)n, where XAA can be any amino acid with the exception of proline, and n can range from tens to hundreds of repeats [25]. Both chemically synthesized polymeric ELPs and recombinantly engineered ELPs exhibit a hallmark thermoresponsive phase separation that is characterized by an inverse transition temperature (Tt) phenomenon [24,25]. In aqueous media with a temperature below that of the Tt, ELPs exist in a solubilized state. However, at temperatures above the Tt, the ELP solutions undergo a coacervation transition, yielding ELP-rich and ELP-poor phases [25]. The value of the Tt can depend on a number of factors including guest residue hydrophobicity, concentration, and ions present in the solution, among many other factors [26]. In general, increased hydrophobicity, increased ELP concentration, and increased ion concentration will all decrease the Tt, and conversely, decreases in these variables lead to increased Tt values [26]. ELPs have been widely used in protein and nanoparticle purification techniques by increasing temperatures above the Tt as a mechanism to precipitate proteins or nanoparticles that are fused or bound with ELPs [25,27]. Exploitation of this temperature responsive coacervation has also been widely used to produce self-assembled structures that can be deployed as novel drug delivery vehicles. To this end, hydrophobic ELPs are generally modified with a hydrophilic moiety (typically in the form of a recombinant protein fusion) to yield amphiphilic molecules that can typically self-assemble above the Tt of the hydrophobic ELP domaininto micelles that can either be spherical or cylindrical in morphology [28]. Such structures have been investigated widely by a number of groups as nanocarriers for small-molecule therapeutics or biologics [28].