Antibacterial and ATP Synthesis Modulating Compounds from Salvia tingitana.

A surface extract of the aerial parts of Salvia tingitana afforded a nor-sesterterpenoid (1) and eight new sesterterpenoids (2-̵9), along with five known sesterterpenoids, five labdane and one abietane diterpenoid, one sesquiterpenoid, and four flavonoids. The structures of the new compounds were established by 1D and 2D NMR spectroscopy, HRESIMS, and VCD data and Mosher's esters analysis. The antimicrobial activity of compounds was evaluated against 30 human pathogens including 27 clinical strains and three isolates of marine origin for their possible implications on human health. The methyl ester of salvileucolide (10), salvileucolide-6,23-lactone (11), sclareol (15), and manool (17) were the most active against Gram-positive bacteria. The compounds were also tested for the inhibition of ATP production in purified mammalian rod outer segments. Terpenoids 10, 11, 15, and 17 inhibited ATP production, while only 17 inhibited also ATP hydrolysis. Molecular modeling studies confirmed the capacity of 17 to interact with mammalian ATP synthase. A significant reduction of ATP production in the presence of 17 was observed in Enterococcus faecalis and E. faecium isolates.

Antibacterial and Hypoglycemic Diterpenoids from Salvia chamaedryoides.

A surface extract of the aerial parts of Salvia chamaedryoides afforded 13 diterpenes (1-13), with seven compounds (1, 3, 4, 7-9, 12) described for the first time. The structures of the new compounds were established using 1D and 2D NMR spectroscopic methods, HRESIMS, and ECD data. The potential hypoglycemic effects of the crude extract, fractions, and pure compounds from S. chamaedryoides were investigated by inhibition of α-glucosidase and α-amylase enzymes. The extract and its fractions showed a moderate dose-dependent inhibition; the pure compounds exhibited differential inhibitory activity against these two enzymes. Molecular modeling studies were also performed to suggest the interaction mode of compound 3 in the α-glucosidase enzyme active site. The antimicrobial activity of the purified compounds was investigated against 26 clinical pathogens. No activity was detected for the Gram-negative species tested nor on Candida albicans and C. glabrata, while variable susceptibilities were observed using Gram-positive staphylococcal and enterococcal species.

Quinolone/fluoroquinolone susceptibility in Escherichia coli correlates with human polymicrobial bacteriuria and with in vitro interleukine-8 suppression.

Urinary tract infections (UTIs) are frequently polymicrobial diseases mainly sustained by Escherichia coli in association with other opportunistic pathogens. Cystitis and pyelonephritis are usually accompanied by an inflammatory response, which includes neutrophil recruitment. Uropathogenic E. coli possess the ability to evade host defenses, modulating the innate immune response. The aim of this study was to determine whether particular E. coli strains correlate with polymicrobial bacteriuria and whether escape from the early host defenses and microbial synergy could lead to mixed UTIs. We evaluated 188 E. coli-positive urine samples and assessed the relationships among polymicrobism, neutrophil presence and several traits of E. coli isolates (virulence factors such as hlyA, fimA, papC and their relative products, i.e. hemolysin, type 1 and P fimbriae, and cnf1, their phylogenetic group) and their ability to suppress cytokine response in 5637 bladder epithelial cells. Escherichia coli susceptibility toward quinolones and fluoroquinolones, known to be linked to the pathogenicity of this species, was also considered. We found significant correlations among polymicrobial bacteriuria, absence of pyuria and quinolone/fluoroquinolone susceptibility of E. coli isolates and their enhanced capability to suppress interleukin-8 urothelial production when compared with the patterns induced by the resistant strains.