Alternatives to anitbiotics

500-700 word literature summary on alternatives to antibiotics (due to antibiotic resistance; finding novel antibiotics) Please see attached instruction.
Minimum of two additional scholarly resources plus reference this redacted discussion of article:
The highly synergistic, broad spectrum, antibacterial activity of organic acids and transition metals
Zhitnitsky, D., J. Rose & O. Lewinson (2017) Scientific Reports, 7:44554. DOI: 10.1038/srep4455
Redacted Discussion
The worldwide rise in bacterial infection-associated morbidity underscores the need to implement novel approaches to limit bacterial growth41. Antibiotics remain the treatment of choice but their excessive and injudicious use has led to high incidences of drug and multidrug-resistant bacterial strains42. Moreover, agricultural use of antibiotics and bactericides results in environmental damage and can lead to widespread and unpredicted harm to wildlife43. It is therefore crucial to find alternatives to conventional antibiotics. In this work we present an inexpensive and viable alternative by simply using combinations of compounds that have relatively low toxicity to humans, animals, and plants. This particular approach is simple, readily applicable and effective. Organic acids are perhaps the most common food preservatives and it would be very simple to add zinc or copper (ordinary dietary supplements) as an additional preservative.
We showed that the common food-borne pathogen Salmonella enterica is poorly inhibited by both organic acids and transition metals, yet completely inhibited by their combination. This was also true for all the other bacterial species that we tested (including pathogens such as Pseudomonas aeruginosa and Vibrio cholerae). We therefore suggest that food preservation can be improved by exploiting the synergistic effect of combining simple organic acids and metals. A similar revision to strategies to protect crops is suggested. World-wide, copper is routinely sprayed on crops, orchards and flowers40. It is often the only available preventive measure in places where antibiotics sprays are banned. However, the copper doses are limited by their toxicity towards plants44 and the efficacy of the sprays are compromised by the emergence of copper-resistant bacterial strains45. We have consistently observed that copper readily combines with all tested organic acids to form a highly potent bactericide that inhibits the growth of the plant pathogens Erwinia amylovora, Pseudomonas syringae and Xanthomonas euvesicatoria. Copper sprays are non-aqueous emulsions that contain fatty acids and other organic compounds and therefore addition of organic acids to these emulsions is straightforward. This sets the stage for a fast, easy and safe transition to a better way to ensure bactericidal effects with limited toxicity to the plants and ecosystems alike.
It is vital to consider the effect that combinations of metals and organic acids may have on the environment as well as on plant or animal cells. The synergistic nature of the inhibitory effect allows the use of much lower concentrations of organic acids and of metals than those used for each of them individually. Thus, the distribution of metal pollutants from crop sprays as well as concentrations of food preservatives may actually decrease by combining organic acids with metals. Furthermore, an adult human can tolerate digestion of up to 10 mg of copper and up to 40 mg of zinc per day46, while copper sprays of potato plants, for example, contain 2.5 grams/ liter concentrations of copper and can tolerate up to 5 grams/liter44. Moreover, synergy growth experiments were performed on two eukaryotic microorganisms, Saccharomyces cerevisiae and Candida albicans. In most cases, little to no synergy was observed. Thus, despite the clear need for further study, based on this data and on our results we believe that the suggested revisions to crop protection and food preservation are likely safe.

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