The emergence of multidrug-resistant Acinetobacter baumannii (MDR-AB), which most commonly manifests as pneumonia, has posed significant clinical challenges and called for novel treatment strategies. Phage depolymerases, which degrade bacterial surface carbohydrates, have emerged as potential antimicrobial agents. However, their preclinical application is limited to systemic infections due to their dependency on serum-mediated bacterial killing. To extend the treatment paradigm of depolymerase to low-serum lung infections, we explored the feasibility of applying phage depolymerase to potentiate antibiotic efficacy in controlling MDR-AB pneumonia. Using a model depolymerase, Dpo71, we observed that it could effectively potentiate antibiotic efficacy against MDR-AB2 bacteria in low-serum conditions mimicking lung milieu but showed no adjuvant effect in serum-free conditions. Unprecedentedly, we reported this low-serum-dependent mechanism that polysaccharide-degrading enzyme Dpo71 exposed bacteria to serum-induced membrane permeabilization and oxidative phosphorylation pathway inhibition, leading to a weakened ATP-dependent efflux pump and strengthened ROS-induced membrane permeabilization. These joint effects facilitated antibiotic (ceftazidime, CFZ) binding, ultimately exerting bactericidal effects. Resultantly, the bacterial load in the lungs of the Dpo71-CFZ combination group was significantly reduced compared with the Dpo71-alone and CFZ-alone groups. Overall, this study unravels the low-serum-dependent mechanisms by which depolymerase potentiated antibiotic efficacy, highlighting its potential as a novel strategy to enhance antibiotic activity against severe pneumonia

serum, Acinetobacter baumannii pneumonia, antibiotic potentiation, multidrug-resistance, phage-derived polysaccharide depolymerases, synergism

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

*O[C@H]1[C@@H](O)[C@@H](CO[C@@H]2O[C@H](CO[C@@]3(C(=O)O)C[C@H](O)[C@H](NC(C)=O)[C@H]([C@@H](NC(C)=O)[C@H](C)O)O3)[C@@H](O)[C@H](O)[C@H]2O)O[C@@H](O[C@@H]2[C@@H](NC(C)=O)[C@H](*)O[C@H](CO)[C@@H]2O)[C@@H]1O

843.786 g/mol (C₃₃H₅₃R₂N₃O₂₂, R = next and previous repeats, not counted in mol weight)

The total polysaccharides extracted from Laetiporus sulphureus fruiting bodies by ultrasound-assisted complex enzyme method were separated by freeze–thaw combined with fehling reagent to prepare purified polysaccharide (LSPS1). The results of monosaccharide composition and molecular weight distribution demonstrated that LSPS1 contained galactose (51.83%), mannose (26.89%), fucose (16.13%) and glucose (5.15%), and the molecular weight was around 17.3 kDa. Methylation analysis indicated that the backbone of LSPS1 consisted of 1,6-Galp residues, branched at O-2 of Galp with t-Manp, t-Fucp and t-Glcp residues as side chains. In addition, LSPS1 was used for the synthesis of SeNPs based on the redox system of sodium selenite and ascorbic acid. The L. sulphureus polysaccharide selenium nanoparticles (LSPS1–SeNPs) were characterized by UV, FT-IR, ICP-MS, EDX, DLS and SEM, inferring that LSPS1–SeNPs were stabilized with spherical and granular surface structure as well as a mean particle size of 96.72 ± 1.12 nm. Both of LSPS1 and LSPS1–SeNPs possessed strong antioxidant and hypoglycemic activities while the effects of LSPS1–SeNPs were superior to LSPS1. The findings provided valuable structural information for L. sulphureus polysaccharide, and will promote the application of SeNPs by L. sulphureus polysaccharide in potential antioxidant agent and hypoglycemic candidate

polysaccharide, Structural characterization, Antioxidant activity, hypoglycemic activity, selenium nanoparticles

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

*OC[C@H]1OC(OC[C@H]2OC(OC[C@H]3OC(OC[C@H]4OC(OC[C@H]5OC(OC[C@H]6OC(OC[C@H]7OC(OC[C@H]8OC(OC[C@H]9OC(OC[C@H]%10OC(OC[C@H]%11OC(*)[C@H](O)[C@@H](O)[C@H]%11O)[C@H](OC%11O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]%11O)[C@@H](O)[C@H]%10O)[C@H](O)[C@@H](O)[C@H]9O)[C@H](OC9O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]9O)[C@@H](O)[C@H]8O)[C@H](OC8O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]8O)[C@@H](O)[C@H]7O)[C@H](O)[C@@H](O)[C@H]6O)[C@H](OC6O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]6O)[C@@H](O)[C@H]5O)[C@H](OC5O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]5O)[C@@H](O)[C@H]4O)[C@H](OC4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)[C@@H](O)[C@H]3O)[C@H](OC3O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]3O)[C@@H](O)[C@H]2O)[C@H](OC2O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]2O)[C@@H](O)[C@H]1O

3048.681 g/mol (C₁₁₄H₁₉₀R₂O₉₃, R = next and previous repeats, not counted in mol weight)

Two new diphenyl ethers (1 and 2) and four new phenolic bisabolane sesquiterpenoids (3-6), together with five known related derivatives, were isolated from the culture of the endophytic fungus Aspergillus flavus QQSG-3 obtained from a fresh branch of Kandelia obobata, which was collected from Huizhou city in the province of Guangdong, China. The structures of compounds 1-6 were determined by analyzing NMR and HRESIMS data. The absolute configurations of 5 and 6 were assigned by comparing their experimental ECD spectra with those reported for similar compounds in the literature. All isolates were evaluated for their -glucosidase inhibitory activity, of which compounds 3, 5, 10, and 11 showed strong inhibitory effects with IC50 values in the range of 1.5-4.5 M.

mangrove endophytic fungus, Aspergillus flavus, α-glucosidase inhibitors

13C NMR data:
Linkage	Residue	C1	C2	C3	C4	C5	C6	C7	C8	C9	C10	C11	C12	C13	C14	C15
7	x?Ery-ol	68.4	71.1	73.1	64.6
	Subst	163.6	103.7	164.9	109.9	144.6	113.1	24.0	172.4	159.9	105.7	157.4	113.6	142.2	113.4	21.5


1H NMR data:
Linkage	Residue	H1	H2	H3	H4	H5	H6	H7	H8	H9	H10	H11	H12	H13	H14	H15
7	x?Ery-ol	4.40-4.62	3.89	3.63	3.65-3.77
	Subst	-	6.23	-	-	-	6.35	2.53	-	-	6.27	-	6.47	-	6.35	2.26


1H/13C HSQC data:
Linkage	Residue	C1/H1	C2/H2	C3/H3	C4/H4	C5/H5	C6/H6	C7/H7	C8/H8	C9/H9	C10/H10	C11/H11	C12/H12	C13/H13	C14/H14	C15/H15
7	x?Ery-ol	68.4/4.40-4.62	71.1/3.89	73.1/3.63	64.6/3.65-3.77
	Subst		103.7/6.23				113.1/6.35	24.0/2.53			105.7/6.27		113.6/6.47		113.4/6.35	21.5/2.26

There are 2 chemically distinct structures. Please, select:
xDEry-ol(1-7)Subst // Subst = 2,6-dihydroxy-4-(3-hydroxy-5-methylphenoxy)benzoic acid = SMILES CC1=C{53}C(O)=CC(OC2=C{6}C(O)=C({2}C(O)=C2){7}C(O)=O)=C1 xLEry-ol(1-7)Subst // Subst = 2,6-dihydroxy-4-(3-hydroxy-5-methylphenoxy)benzoic acid = SMILES CC1=C{53}C(O)=CC(OC2=C{6}C(O)=C({2}C(O)=C2){7}C(O)=O)=C1

SVGMWSMILES3D molIonize

 

Cc1cc(O)cc(Oc2cc(O)c(C(=O)OC[C@H](O)[C@H](O)CO)c(O)c2)c1

380.349 g/mol (C₁₈H₂₀O₉)

Among the major cardenolides from the milkweed Asclepias asperula, 6'-O-(E-4-hydroxycinnamoyl) desglucouzarin has not been characterized biochemically. In this study, its binding affinity for a physiological receptor, porcine kidney Na+,K+-ATPase, was found to be lower than the other cardenolides in this plant. The order of affinities from highest to lowest was: uzarigenin (K(d) = 1.05 μM) = desglucouzarin (K(d) = 0.98 μM) > uzarin (K(d) = 4.0 μM) > 6'-O-(E-4-hydroxycinnamoyl) desglucouzarin (K(d) = 16 μM). The chemical attachment of the 4-hydroxycinnamoyl group to the 6'-carbon of desglucouzarin significantly inhibits binding. This agrees with predictions that a 5'-methyl group on cardenolides fits the receptor site optimally for the porcine kidney enzyme. The 4-hydroxycinnamic ester was also found to be fluorescent.

enzyme inhibitor, cardiac glycoside, cardenolide, Asclepias, Asclepias asperula, desglucouzarin, kidney enzyme, urarin, uzarigenin

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

C[C@]12CC[C@H](O[C@@H]3O[C@H](COC(=O)/C=C/c4ccc(O)cc4)[C@@H](O)[C@H](O)[C@H]3O)C[C@@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](C3=CC(=O)OC3)CC[C@]12O

682.807 g/mol (C₃₈H₅₀O₁₁)