The efficacy and immunogenicity of a live transconjugant hybrid strain of <Emphasis Type="Italic">Shigella dysenteriae</Emphasis> type 1 in two animal models

In our earlier studies, we constructed a hybrid strain of Shigella dysenteriae type 1 by introducing a plasmid vector pPR 1347. After introduction of a lipopolysaccharide (LPS) biosynthesis gene, virulent Shigella dysenteriae type 1 strain became avirulent. In our present study, we have evaluated the immune response and protective efficacy of avirulent live transconjugant Shigella hybrid (LTSH) strain against wild type Shigella dysenteriae type 1, after four doses of oral (rabbit) and intranasal (mouse) immunizations. Serum IgG titers showed exponential increase during immunization and peaking on the 28th day and remained at that level till the 35th day in both the rabbit and the mouse models. When tested, serum IgG titers persisted for 63 days in mice and relatively high for 150 days in case of rabbits. Protection studies showed 100% protection against the challenge with wild type Shigella dysenteriae type 1 strain in rabbits and 80% protection in mice. Our results suggested that the LTSH strain could be a useful vaccine candidate strain in the future.     

Passive immunity with multi‐serotype heat‐killed Shigellae in neonatal mice

The short‐ and long‐term passive protective efficacy of a mixture of heat‐killed cells of six serogroups/serotypes of Shigella strains (Shigella dysenteriae 1, S. flexneri 2a, S. flexneri 3a, S. flexneri 6, S. boydii 4, and S. sonnei) were studied in neonatal mice. Neonatal mice from immunized dams exhibited significant short‐ and long‐term passive protection against individual challenge by each of the six Shigella strains. High IgG and IgA titers against the lipopolysaccharide from each of the six Shigella strains were observed in sera from immunized dams.     

Organoiridium complexes: efficient catalysts for the formation of sugar acetals and ketals

[Cp^∗IrCl₂]₂ is used as an efficient promoter for the synthesis of sugar acetals and ketals with good to excellent yields. The catalyst is found to be general for a wide range of sugars.     

Naphthoquinone-mediated Inhibition of Lysine Acetyltransferase KAT3B/p300, Basis for Non-toxic Inhibitor Synthesis

Hydroxynaphthoquinone-based inhibitors of the lysine acetyltransferase KAT3B (p300), such as plumbagin, are relatively toxic. Here, we report that free thiol reactivity and redox cycling properties greatly contribute to the toxicity of plumbagin. A reactive 3rd position in the naphthoquinone derivatives is essential for thiol reactivity and enhances redox cycling. Using this clue, we synthesized PTK1, harboring a methyl substitution at the 3rd position of plumbagin. This molecule loses its thiol reactivity completely and its redox cycling ability to a lesser extent. Mechanistically, non-competitive, reversible binding of the inhibitor to the lysine acetyltransferase (KAT) domain of p300 is largely responsible for the acetyltransferase inhibition. Remarkably, the modified inhibitor PTK1 was a nearly non-toxic inhibitor of p300. The present report elucidates the mechanism of acetyltransferase activity inhibition by 1,4-naphthoquinones, which involves redox cycling and nucleophilic adduct formation, and it suggests possible routes of synthesis of the non-toxic inhibitor.     

Factors associated with in-hospital mortality of adult tetanus patients–a multicenter study from Bangladesh

BackgroundTetanus, a vaccine-preventable disease, is still occurring in the elderly population of low- and middle-income countries with a high case-fatality rate. The objective of the study was to elucidate the factors associated with in-hospital mortality of tetanus in Bangladesh.MethodsThis prospective observational study, conducted in two specialized infectious disease hospitals, conveniently selected adult tetanus patients (≥18 years) for inclusion. Data were collected through a preformed structured questionnaire. Kaplan Meier survival analysis and univariate and multivariable Cox regression analysis were carried out to assess factors associated with in-hospital mortality among patients. All analysis was done using Stata (version 16) and SPSS (version 26).ResultsA total of 61 tetanus cases were included, and the overall in-hospital mortality rate was 34.4% (n = 21). Patients had an average age of 46.49 ±15.65 years (SD), and the majority were male (96.7%), farmers (57.4%), and came from rural areas (93.4%). Survival analysis revealed that the probability of death was significantly higher among patients having an age of ≥ 40 years, incubation time of ≤12 days, onset time of ≤ 4 days, and having complication(s). However, on multivariable Cox regression analysis, age (adjusted hazard ratio [aHR] 4.03, 95% Confidence Interval [CI] 1.07–15.17, p = 0.039) and onset time (≤4 days) (aHR 3.33; 95% CI 1.05–10.57, p = 0.041) came as significant predictors of in-hospital mortality after adjusting for incubation period and complications.ConclusionOlder age and short onset time are the two most important determinants of in-hospital mortality of tetanus patients. Hence, these patients require enhanced emphasis and care.     

Live non-invasive Shigella dysenteriae 1 strain induces homologous protective immunity in a guinea pig colitis model

A non-invasive live transconjugant Shigella hybrid (LTSHΔstx) strain was constructed from a Shiga toxin gene deleted mutant of Shigella dysenteriae 1 by introducing a plasmid vector pPR1347 that carried a lipopolysaccharide biosynthesis gene (rfb and rfc) of Salmonella typhimurium. In guinea pigs, four successive oral administrations of LTSH Δstx showed complete protection against rectal challenge with wild type S. dysenteriae 1 strain. Exponential increase of the serum IgG and IgA titer against lipopolysaccharide of LTSH Δstx was observed during immunization, peaked on day 28 and remained at that level until day 35 after the initiation of the immunization. In intestinal lavage of the immunized animals, significant increase of IgA titer against lipopolysaccharide of LTSH Δstx was also observed. These data suggested that LTSH Δstx could be a useful candidate to induce protective immunity against S. dysenteriae 1 infection.     

In silico structural,functional and phylogenetic analysis of <Emphasis Type="Italic">Klebsiella</Emphasis> phytases

Phytic acid or phytate (myo-inositol hexakisphosphate) is the principal storage indigestible form of phosphorus in different crops. It is considered as an antinutrient in human as well as animal (including fish, poultry, pig, chicken etc.) diet due to its chelating behavior of certain essential divalent minerals (Fe²⁺, Mg²⁺, Zn²⁺, Ca²⁺ etc.). The unabsorbed, indigested form of phosphorus also causes phosphate pollution in the soil by animal wastes. Phytate degrading enzymes like phytases (myo-inositol hexakisphosphate phosphohydrolase) in this regard can be very useful and also economically feasible to reduce the risk of phosphate pollution and increase the nutrient value in animal feeds at the same time. The Klebsiella phytases are suitable to use in the food industries of plant origin for their excellent thermal stability and high pH tolerance. From the present in silico investigation, it was found that Klebsiella phytases were 46–47 kDa molecular weight protein of histidine phosphatase superfamily having thermostability and alkalinity nature. This thermostability can be achieved due to possession of higher percentage of α helices and β sheets at the same time; the presence of higher aliphatic indices (range in between 88 and 91) etc. Interestingly, a strong correlation was found to be pertinent from phylogenetic studies of proteins with their cDNA among both species and strain level. Hence, the present study would be beneficial for future researchers (3D model available in Protein Model Database with acc. no.: PM0080562) to meet the demand of agricultural and industrial production of bacterial phytases particularly for agricultural farming.     

FeCl3 mediated arylidenation of carbohydrates

Glycosides and thioglycosides based on monosaccharides in reaction with benzaldehyde dimethylacetal or p-methoxybenzaldehyde dimethyl acetal undergo FeCl₃-catalyzed (20 mol %) regioselective 4,6-O-arylidenation producing the corresponding acetals in high yields. FeCl₃ also mediates acetalation of glycosides and thioglycosides of cellobiose, maltose, and lactose affording the corresponding 4′,6′-O-benzylidene acetals, which were isolated after their acetylation in situ with acetic anhydride and pyridine. The combined yields (two steps) of these final products are also high (61–84%). The procedure is applicable to a wide variety of functional groups including –OBn.     

Aryl 4,6-O-arylidene-1-thio-beta-d-glycopyranoside-based new organogelators and their gels

Aryl 4,6-O-arylidene-1-thio-beta-d-glycopyranosides based on glucose and galactose form organogels in benzene, toluene, o- and p-xylene and 1,2,3,4-tetrahydronaphthalene. The gel morphologies of micro and nano dimensions were studied using SEM and TEM. Absorption spectroscopic studies of two organogels in benzene revealed that CH-pi or pi-stacking along with intermolecular H-bonding is responsible for the gel assembly.