scholarly journals Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

2021 ◽  
Vol 17 ◽  
pp. 2915-2921
Author(s):  
Tanmoy Halder ◽  
Somnath Yadav

Capsular polysaccharides of pathogenic bacteria have been reported to be effective vaccines against diseases caused by them. Providencia stuartii is a class of enterobacteria of the family Providencia that is responsible for several antibiotic resistant infections, particularly urinary tract infections of patients with prolonged catheterization in hospital settings. Towards the goal of development of vaccine candidates against this pathogen, we herein report the total synthesis of a trisaccharide repeating unit of the O-antigen polysaccharide of the P. stuartii O49 serotype containing the →6)-β-ᴅ-Galp-(1→3)-β-ᴅ-GalpNAc(1→4)-α-ᴅ-Galp(1→ linkage. The synthesis of the trisaccharide repeating unit was carried out first by a linear strategy involving the [1 + (1 + 1 = 2)] assembly, followed by a one-pot synthesis involving [1 + 1 + 1] strategy from the corresponding monosaccharides. The one-pot method provided a higher yield of the protected trisaccharide intermediate (73%) compared to the two step synthesis (66%). The protected trisaccharide was then deprotected and N-acetylated to finally afford the desired trisaccharide repeating unit as its α-p-methoxyphenyl glycoside.

1987 ◽  
Vol 8 (6) ◽  
pp. 241-244 ◽  
Author(s):  
Maury E. Mulligan ◽  
Y.Y. Kwok

AbstractCefixime, a broad-spectrum, orally active cephalosporin, was more active in vitro than ampicillin, cefaclor, cephalothin, and trimethoprim/sulfamethoxazole against 194 nosocomial pathogens of the family Enterobacteriaceae. Activity was especially good against Klebsiella spp, Proteus spp, Serratia spp, and Providencia stuartii. Although gentamicin had equivalent or better activity against Citrobacter spp, Enterobacter spp, Escherichia coli, and Morganella morganii, all 23 of the gentamicin-resistant strains studied were susceptible to Cefixime. Isolates tested were from urinary tract infections, abdominal infections, wounds, vascular infections, and respiratory infections; they were sequentially collected nosocomial pathogens from a single institution. This orally active cephalosporin should be considered for therapy of a variety of nosocomial infections involving gram-negative bacillary pathogens.


2015 ◽  
Vol 13 (14) ◽  
pp. 4240-4247 ◽  
Author(s):  
Jiachen Xiang ◽  
Jungang Wang ◽  
Miao Wang ◽  
Xianggao Meng ◽  
Anxin Wu

This paper described a decarboxylative deaminative dual-coupling reaction of amino acids with indoles to afford BIM scaffolds and its further application to the one-pot total synthesis of natural products.


Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 375
Author(s):  
Chani Rakov ◽  
Shira Ben Porat ◽  
Sivan Alkalay-Oren ◽  
Ortal Yerushalmy ◽  
Mohanad Abdalrhman ◽  
...  

Providencia spp. are emerging pathogens mainly in nosocomial infections. Providencia stuartii in particular is involved in urinary tract infections and contributes significantly to the high incidence of biofilm-formation in catheterized patients. Furthermore, recent reports suggested a role for multiple drug resistant (MDR) P. stuartii in hospital-associated outbreaks which leads to excessive complications resulting in challenging treatments. Phage therapy is currently one of the most promising solutions to combat antibiotic-resistant infections. However, the number of available phages targeting Providencia spp. is extremely limited, restricting the use of phage therapy in such cases. In the present study, we describe the isolation and characterization of 17 lytic and temperate bacteriophages targeting clinical isolates of Providencia spp. as part of the Israeli Phage Bank (IPB). These phages, isolated from sewage samples, were evaluated for host range activity and effectively eradicated 95% of the tested bacterial strains isolated from different geographic locations and displaying a wide range of antibiotic resistance. Their lytic activity is demonstrated on agar plates, planktonic cultures, and biofilm formed in a catheter model. The results suggest that these bacteriophages can potentially be used for treatment of antibiotic-resistant Providencia spp. infections in general and of urinary tract infections in particular.


2019 ◽  
Author(s):  
Zhenguang Zhao ◽  
Norman Metanis

<p>While chemical protein synthesis (CPS) has granted access to challenging proteins, synthesis of longer proteins is often limited by low abundance or non-strategic placement of cysteine (Cys) residues, essential for native chemical ligations (NCL), as well as multiple purification and isolation steps. Selective deselenization and one-pot CPS serve as key technologies to circumvent these issues. Herein, we describe the one-pot total synthesis of human thiosulfate: glutathione sulfurtransferase (TSTD1), a 115-residue protein with a single Cys residue at its active site, and its seleno-analogue. WT-TSTD1 was synthesized in a C-to-N synthetic approach employing multiple NCL reactions, Cu(II)-mediated deprotection of selenazolidine (Sez), and chemoselective deselenization, all in one-pot. In addition, the protein’s seleno analogue (Se-TSTD1), in which the active site Cys is replaced with selenocysteine, was synthesized with a kinetically controlled ligation in a one-pot, N-to-C synthetic approach. TSTD1’s one-pot synthesis was made possible by the newly reported, rapid, and facile copper-mediated selenazolidine deprotection that can be accomplished in one minute. Finally, catalytic activity of the two proteins indicated that Se-TSTD1 possessed only four-fold lower activity than WT-TSTD1 as a thiosulfate: glutathione sulfurtransferase, suggesting that selenoproteins can have physiologically comparable sulfutransferase activity as their cysteine counterparts. </p>


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2423 ◽  
Author(s):  
Luis Amarillas ◽  
Cristóbal Chaidez ◽  
Arturo González-Robles ◽  
Yadira Lugo-Melchor ◽  
Josefina León-Félix

BackgroundShiga toxin-producingEscherichia coli(STEC) is one of the most common and widely distributed foodborne pathogens that has been frequently implicated in gastrointestinal and urinary tract infections. Moreover, high rates of multiple antibiotic-resistantE. colistrains have been reported worldwide. Due to the emergence of antibiotic-resistant strains, bacteriophages are considered an attractive alternative to biocontrol pathogenic bacteria. Characterization is a preliminary step towards designing a phage for biocontrol.MethodsIn this study, we describe the characterization of a bacteriophage designated phiC119, which can infect and lyse several multidrug-resistant STEC strains and someSalmonellastrains. The phage genome was screened to detect thestx-genes using PCR, morphological analysis, host range was determined, and genome sequencing were carried out, as well as an analysis of the cohesive ends and identification of the type of genetic material through enzymatic digestion of the genome.ResultsAnalysis of the bacteriophage particles by transmission electron microscopy showed that it had an icosahedral head and a long tail, characteristic of the familySiphoviridae. The phage exhibits broad host range against multidrug-resistant and highly virulentE. coliisolates. One-step growth experiments revealed that the phiC119 phage presented a large burst size (210 PFU/cell) and a latent period of 20 min. Based on genomic analysis, the phage contains a linear double-stranded DNA genome with a size of 47,319 bp. The phage encodes 75 putative proteins, but lysogeny and virulence genes were not found in the phiC119 genome.ConclusionThese results suggest that phage phiC119 may be a good biological control agent. However, further studies are required to ensure its control of STEC and to confirm the safety of phage use.


Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1002 ◽  
Author(s):  
Eunsu Ha ◽  
Jihwan Chun ◽  
Minsik Kim ◽  
Sangryeol Ryu

Clostridium perfringens is a Gram-positive, anaerobic, and spore forming bacterium that is widely distributed in the environment and one of the most common causes of foodborne illnesses. Bacteriophages are regarded as one of the most promising alternatives to antibiotics in controlling antibiotic-resistant pathogenic bacteria. Here we isolated a virulent C. perfringens phage, CPS1, and analysis of its whole genome and morphology revealed a small genome (19 kbps) and a short noncontractile tail, suggesting that CPS1 can be classified as a member of Picovirinae, a subfamily of Podoviridae. To determine the host receptor of CPS1, the EZ-Tn5 random transposon mutant library of C. perfringens ATCC 13124 was constructed and screened for resistance to CPS1 infection. Analysis of the CPS1-resistant mutants revealed that the CPF_0486 was disrupted by Tn5. The CPF_0486 was annotated as galE, a gene encoding UDP-glucose 4-epimerase (GalE). However, biochemical analyses demonstrated that the encoded protein possessed dual activities of GalE and UDP-N-acetylglucosamine 4-epimerase (Gne). We found that the CPF_0486::Tn5 mutant produced a reduced amount of capsular polysaccharides (CPS) compared with the wild type. We also discovered that glucosamine and galactosamine could competitively inhibit host adsorption of CPS1. These results suggest that CPS acts as a receptor for this phage.


Synthesis ◽  
2017 ◽  
Vol 49 (18) ◽  
pp. 4357-4371 ◽  
Author(s):  
Joaquín Tamariz ◽  
R. Hernández-Benitez ◽  
Daniel Zárate-Zárate ◽  
Francisco Delgado

The scope and limitations of the strategy for the conversion of 2-anilinocyclohexenones and N-arylcyclohexane enaminones into the 1- and 2-oxygenated carbazole scaffolds, respectively, were evaluated. The one-pot palladium(0)-catalyzed aromatization/methylation process of the aforementioned substrates provided a diversity of the corresponding diarylamines. A subsequent palladium(II)-catalyzed cyclization of the latter delivered the desired 1- and 2-oxygenated carbazoles in good overall yields. Special attention was given to the synthesis of the uncommon 1,8-disubstituted carbazoles. This methodology was employed for the total synthesis of the naturally occurring clauraila A, clausenal, clausine P, and 7-methoxy-O-methylmukonal.


2015 ◽  
Vol 3 (03) ◽  
pp. 07-11 ◽  
Author(s):  
Janbee Shaik ◽  
Vishakha K ◽  
Ramyasree D

There are many plants used by tribunal people as an anti bacterial, among them myrrh is the one which is commonly used. Myrrh is an oleo gum resin obtained from the plant Commiphora myrrha belongs to the family Burceraceae. It can adhere to intestines because of its resinous nature and it reduces the acidity in small intestines. Generally, the resin is collected from bark and stem of the plant by the process incision. In present study ethyl acetate extract of Commiphora myrrha was used for the evaluation of Anti bacterial activity against three Gram negative organisms and two Gram positive organisms. The method used in evaluation of Anti bacterial activity was serial dilution and Agar Diffusion method. The antibacterial activity was calculated in terms of minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC). The antibacterial activity was compared with marketed antibiotic.


2021 ◽  
Author(s):  
Chani Rakov ◽  
Shira Ben Porat ◽  
Sivan Alkalay-Oren ◽  
Ortal Yerushalmy ◽  
Mohanad Abdalrhman ◽  
...  

AbstractProvidencia spp. are emerging pathogens mainly in nosocomial infections. Providencia stuartii in particular is involved in urinary tract infections and contributes significantly to the high incidence of biofilm-formation in catheterized patients. Furthermore, recent reports suggested a role for multiple drug resistant (MDR) P. stuartii in hospital-associated outbreaks which leads to excessive complications resulting in challenging treatments. Phage therapy is currently one of the most promising solutions to combat antibiotic-resistant infections. However, the number of available phages targeting Providencia spp. is extremely limited, restricting the use of phage therapy in such cases. In the present study, we describe the isolation and characterization of 17 lytic and lysogenic bacteriophages targeting clinical isolates of Providencia spp. as part of the Israeli Phage Bank (IPB). These phages, isolated from sewage samples, were evaluated for host range activity and effectively eradicated 95% of the tested bacterial strains isolated from different geographic locations and displaying a wide range of antibiotic resistance. Their lytic activity is demonstrated on agar plates, planktonic cultures, and biofilm formed in a catheter model. The results suggest that these bacteriophages can potentially be used for treatment of antibiotic-resistant Providencia spp. infections in general and of urinary tract infections in particular.


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