Shigellosis is an endemic diarrheal disease caused by Gram negative bacteria named Shigella. The most exposed polysaccharides of Shigella sonnei display a zwitterionic disaccharide repeating unit (AB) made of two rare amino sugars: [4)-α- l -AltpNAcA-(1→3)-β- d -FucpNAc4N-(1→]. An original synthesis of a ready-for-oligomerization AB disaccharide is reported. The targeted orthogonally protected disaccharide was synthesized from l -glucose and tetra-O-acetyl-β- d -glucosamine. The challenging introduction of the 4B-azido group masking the amino moiety of the AAT residue was performed at the disaccharide stage by a two-step procedure (triflation followed by nucleophilic displacement with NaN3). A post-glycosylation oxidation strategy was employed to access the altruronate moiety.
Abstract A major threat to the world is the emergence of antibiotic resistant bacteria, which has rendered previously susceptible drugs useless and increased the rate of therapeutic failures. Shigella species, which are the causative organism of Shigellosis, were earlier susceptible to ampicillin, chloramphenicol, co-trimoxazole and nalidixic acid but now they have developed resistance against fluoroquinolones, cephalosporins and azithromycin. Many shigellosis outbreaks have been reported by res...
Summary Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides an up-to-date analysis of the burden of diarrhoeal diseases. This study assesses cases, deaths, and aetiologies spanning the past 25 years and informs the changing picture of diarrhoeal disease worldwide. Methods We estimated diarrhoeal mortality by age, sex, geography, and year using the Cause of Death Ensemble Model (CODEm), a modelling platform shared across most causes of death in the ...
The Gram-positive bacterium Streptococcus pneumoniae causes severe disease globally. Vaccines that prevent S. pneumoniae infections induce antibodies against epitopes within the bacterial capsular polysaccharide (CPS). A better immunological understanding of the epitopes that protect from bacterial infection requires defined oligosaccharides obtained by total synthesis. The key to the synthesis of the S. pneumoniae serotype 12F CPS hexasaccharide repeating unit that is not contained in currently...
Last. Eric R. Houpt(UVA: University of Virginia)H-Index: 68
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Summary Background Diarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS). Methods GEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia. We used quantitative real-time PCR (qPCR) to test for ...
Shigella sonnei O-antigen features a zwitterionic disaccharide repeat encompassing two rare monosaccharides. The synthesis of the AB repeat and of trisaccharides ABA′ and B′AB, which validates chain elongation at either end, is reported. All targets were synthesized using a postglycosylation oxidation strategy in combination with imidate chemistry. Precursors to residue A were obtained from l-glucose. The AAT (B) donor and acceptor were obtained from d-glucosamine. A one-step Pd(OH)2/C-mediated ...
Last. Myron M. Levine(UMB: University of Maryland, Baltimore)H-Index: 145
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Shigella infection continues to have a high disease burden worldwide, especially in young children in developing countries. Here, the latest progress in Shigella vaccine research is reviewed—including the identification of new vaccine antigens and technological advances in vaccine design and manufacture—as well as the barriers that impede the development of a successful Shigella vaccine.
Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery(1,2), spreading efficiently via low-dose fecal-oral transmission(3,4). Historically, S. sonnei has been predominantly responsible for dysentery in developed countries but is now emerging as a problem in the developing world, seeming to replace the more diverse Shigella flexneri in areas undergoing economic development and improvements in water quality(4-6). Classical approa...
A novel derivative of 2′,4′-bridged nucleic acid, named hydroxamate-bridged nucleic acid (HxNA), containing a six-membered perhydro-1,2-oxazin-3-one ring, was designed and synthesized. The introduction of a carbonyl function along with an N–O linkage in the six-membered bridged structure is the unique structural feature of the novel 2′,4′-bridged nucleic acid analogue. The design was carried out to restrict the flexibility of the sugar moiety through the trigonal planarity of carbonyl function, ...
#1Xiangyang Wu(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 6
#2Lina Cui(University of California, Berkeley)H-Index: 12
Last. David R. Bundle(U of A: University of Alberta)H-Index: 71
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Zwitterionic polysaccharides (ZPSs) from Bacteroides fragilis and Streptococcus pneumoniae display unique T-cell activities. The first synthesis of a hexasaccharide representing two repeating units of the zwitterionic capsular polysaccharide from S. pneumoniae type 1 (Sp1) is reported. Key elements of the approach are stereoselective construction of 1,4-cis-α-galactose linkages based on a reactive trichloroacetimidate donor that incorporates a 6-O-acetyl group, which may contribute to the high α...
Last. Rachel Schneerson(NIH: National Institutes of Health)H-Index: 66
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Abstract Background Despite its high worldwide morbidity and mortality, there is yet no licensed vaccine for shigellosis. We reported the safety and immunogenicity of Shigella O-specific polysaccharide–protein conjugates in adults and young children and efficacy of Shigella sonnei conjugate in young adults. Methods A double-blinded, randomized and vaccine-controlled Phase 3 evaluation of S. sonnei and Shigella flexneri 2a O-SP–rEPA conjugates, 25 μg, injected IM twice, 6 weeks apart, into health...
Zwitterionic carbohydrate modifications, such as phosphoethanolamine (PEtN), govern host-pathogen interactions. Whereas it is recognized that these modifications stimulate the host immune system, the purpose of PEtN modification remains largely descriptive. As an enabling step toward studying this carbohydrate modification, we report a synthesis of the P. temperata zwitterionic trisaccharide repeating unit. The 32-step synthesis was enabled by H-phosphonate chemistry to install the PEtN arm on a...
Shigella sonnei surface polysaccharides are well-established protective antigens against this major cause of diarrhoeal disease. They also qualify as unique zwitterionic polysaccharides (ZPSs) featuring a disaccharide repeating unit made of two 1,2-trans linked rare aminodeoxy sugars, a 2-acetamido-2-deoxy-l-altruronic acid (l-AltpNAcA) and a 2-acetamido-4-amino-2,4,6-trideoxy-d-galactopyranose (AAT). Herein, the stereoselective synthesis of S. sonnei oligosaccharides comprising two, three and f...
ABSTRACT Salbutamol (SAL), a short-acting β-2 adrenergic receptor agonist, is an undesirable addition to livestock farming and used to improve the growth rates. A direct competitive colorimetric immunoassay for SAL was developed. The alkaline phosphatase (ALP)-mediated controlled growth of the prereduction silver nanoparticles (AgNPs) was used to achieve the highly sensitive, colorimetric detection of SAL through the plasmonic ELISA. Click chemistry reaction was used to synthesize salbutamol bio...
Zwitterionic polysaccharides (ZPs) have been shown in recent years to display peculiar immunological properties, thus attracting the interest of the carbohydrate research community. To fully elucidate the mechanisms underlying these properties and exploit the potential of this kind of structures, in depth studies are still required. In this context, the preparation of two cationic, an anionic, as well as two zwitterionic tetrasaccharide analogues of the smallest immunogenic structure of Streptoc...
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