In-depth characterization of antibacterial activity of melittin against Staphylococcus aureus and use in a model of non-surgical MRSA-infected skin wounds.

Skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) require the development of new and effective topical antibiotics. In this context, melittin, the main component of apitoxin, has a potent antibacterial effect. However, little is known regarding the anti-inflammatory potential this peptide in infection models, or its ability to induce clinically important resistance. Here, we aimed to conduct an in-depth characterization of the antibacterial potential of melittin in vitro and evaluate the pharmaceutical potential of an ointment containing melittin for the treatment of non-surgical infections induced by MRSA. The minimum inhibitory concentration of melittin varied from 0.12 to 4 µM. The antibacterial effect was mainly bactericidal and fast (approximately 0.5 h after incubation) and was maintained even in stationary cells and mature MRSA biofilms. Melittin interacts synergistically with beta-lactams and aminoglycosides, and its ability to form pores in the membrane reverses the resistance of vancomycin-intermediate Staphylococcus aureus (VISA) to amoxicillin, and vancomycin. Its ability to induce resistance in vitro was absent, and melittin was stable in several conditions often associated with infected wounds. In vivo, aointment containing melittin reduced bacterial load and the content of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6 (IL-6), and IL-1 beta. Collectively, these data point to melittin as a potential candidate for topical formulations aimed at the treatment of non-surgical infections caused by MRSA.

Ciprofloxacin vs. temperature: Antibiotic toxicity in the free-floating liverwort Ricciocarpus natans from a climate change perspective.

The physiological responses of the aquatic liverwort Ricciocarpus natans to ciprofloxacin (Cipro) exposure under different growth temperatures were investigated. Cipro appears to act as an inhibitor of mitochondrial Complex III by blocking the oxidation of quinol, resulting in the formation of hydrogen peroxide (H2O2). H2O2 accumulation upon Cipro exposure is responsible for decreased photosynthesis in plants. The amount of H2O2 in plants is kept under control by antioxidant enzymes, whose activities are central to the responses of plants to Cipro yet are influenced by temperature. Increased temperature favored Cipro uptake by plants as well as its deleterious effects on mitochondrial activity; however, it also favored the activity of antioxidant enzymes, thereby preventing the exacerbation of the deleterious effects of Cipro. The uptake of Cipro by plants appears to be largely a passive process, although some uptake must be driven by an energy-consuming process. Ricciocarpus natans should be considered for programs aimed at the reclamation of Cipro since this plant exhibits high Cipro-tolerance, the capacity for accumulation and increased uptake rates of the antibiotic with increasing temperatures (from 20 to 30 °C).

Responses of the nitrogen-fixing aquatic fern Azolla to water contaminated with ciprofloxacin: Impacts on biofertilization.

We investigated the ability of the aquatic fern Azolla to take up ciprofloxacin (Cipro), as well as the effects of that antibiotic on the N-fixing process in plants grown in medium deprived (-N) or provided (+N) with nitrogen (N). Azolla was seen to accumulate Cipro at concentrations greater than 160 µg g-1 dry weight when cultivated in 3.05 mg Cipro l-1, indicating it as a candidate for Cipro recovery from water. Although Cipro was not seen to interfere with the heterocyst/vegetative cell ratios, the antibiotic promoted changes with carbon and nitrogen metabolism in plants. Decreased photosynthesis and nitrogenase activity, and altered plant's amino acid profile, with decreases in cell N concentrations, were observed. The removal of N from the growth medium accentuated the deleterious effects of Cipro, resulting in lower photosynthesis, N-fixation, and assimilation rates, and increased hydrogen peroxide accumulation. Our results shown that Cipro may constrain the use of Azolla as a biofertilizer species due to its interference with nitrogen fixation processes.

Ciprofloxacin induces oxidative stress in duckweed (Lemna minor L.): Implications for energy metabolism and antibiotic-uptake ability.

We investigate the physiological responses and antibiotic-uptake capacity of Lemna minor exposed to ciprofloxacin. Ciprofloxacin (Cipro) induced toxic effects and hormesis in plants by significantly modifying photosynthesis and respiration pathways. A toxic effect was induced by a concentration ≥1.05mg ciprofloxacin l-1 while hormesis occurs at the lowest concentration studied (0.75mg ciprofloxacin l-1). By impairing normal electron flow in the respiratory electron transport chain, ciprofloxacin induces hydrogen peroxide (H2O2) production. The ability of plants to cope with H2O2 accumulation using antioxidant systems resulted in stimulation/deleterious effects to photosynthesis by Cipro. Cipro-induced oxidative stress was also associated with the ability of L. minor plants to uptake the antibiotic and, therefore, with plant-uptake capacity. Our results indicate that instead of being a photosystem II binding molecule, Cipro induces oxidative stress by targeting the mitochondrial ETC, which would explain the observed effects of the antibiotic on non-target eukaryotic organisms. The selection of plants species with a high capacity to tolerate oxidative stress may constitute a strategy to be used in Cipro-remediation programs.