Synthesis and characterisation of antimicrobial metal-organic frameworks as multi-drug carriers.

Antibiotic resistance is a significant global concern, necessitating the development of either new antibiotics or advanced delivery methods. With this in mind, we report on the synthesis and characterisation of a new family of Metal-Organic Frameworks (MOFs), OnG6 MOFs, designed to act as multi-drug carriers for bacterial infection treatment. OnG6 is based on the pro-drug 4,4'-azodisalicylic acid (AZDH4), which in vivo produces two equivalents of para-aminosalicylic acid (ASA), a crucial drug for M. tuberculosis treatment. X-ray and computational studies revealed that OnG6 MOFs are mesoporous MOFs with etb topology and an [M2(AZD)] formula (M = Zn, OnG6-Zn; Mg, OnG6-Mg; Cu, OnG6-Cu; and Co, OnG6-Co), featuring 1-dimensional channel type pores of 25 Å diameter. OnG6 MOFs are the first reported MOFs bearing the ligand AZDH4, joining the family of mesoporous MOFs arranged in a honeycomb pattern. They absorb isoniazid (INH) and ciprofloxacin (CIPRO) with the former being a specific antibiotic for M. tuberculosis, and the latter being a broader-spectrum antibiotic. The stability of the MOFs and their capacity for antibiotic uptake depend on the nature of the metal ion, with OnG6-Mg demonstrating the highest drug absorption. The antimicrobial activity of these species was assessed against S. aureus and E. coli, revealing that the carriers containing CIPRO displayed optimal efficacy.

Inhibition of bacterial biofilms by the snake venom proteome.

Snake venoms possess a range of pharmacological and toxicological activities. Here we evaluated the antibacterial and anti-biofilm activity against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) of venoms from the Samar spitting cobra Naja samarensis and the Puff adder Bitis arietans. Both venoms prevented biofilm production by pathogenic S. aureus in a growth-independent manner, with the B. arietans venom being most potent. Fractionation showed the active molecule to be heat-labile and >10 kDa in size. Proteomic profiles of N. samarensis venom revealed neurotoxins and cytotoxins, as well as an abundance of serine proteases and three-finger toxins, while serine proteases, metalloproteinases and C-lectin types were abundant in B. arietans venom. These enzymes may have evolved to prevent bacteria colonising the snake venom gland. From a biomedical biotechnology perspective, they have valuable potential for anti-virulence therapy to fight antibiotic resistant microbes.

Worldwide Web: High Venom Potency and Ability to Optimize Venom Usage Make the Globally Invasive Noble False Widow Spider Steatoda nobilis (Thorell, 1875) (Theridiidae) Highly Competitive against Native European Spiders Sharing the Same Habitats.

Venom compositions include complex mixtures of toxic proteins that evolved to immobilize/dissuade organisms by disrupting biological functions. Venom production is metabolically expensive, and parsimonious use is expected, as suggested by the venom optimisation hypothesis. The decision-making capacity to regulate venom usage has never been demonstrated for the globally invasive Noble false widow Steatoda nobilis (Thorell, 1875) (Theridiidae). Here, we investigated variations of venom quantities available in a wild population of S. nobilis and prey choice depending on venom availability. To partially determine their competitiveness, we compared their attack rate success, median effective dose (ED50) and lethal dose (LD50), with four sympatric synanthropic species: the lace webbed spider Amaurobius similis, the giant house spider Eratigena atrica, the missing sector orb-weaver Zygiella x-notata, and the cellar spider Pholcus phalangioides. We show that S. nobilis regulates its venom usage based on availability, and its venom is up to 230-fold (0.56 mg/kg) more potent than native spiders. The high potency of S. nobilis venom and its ability to optimize its usage make this species highly competitive against native European spiders sharing the same habitats.