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      Pharmaceutical Potential of Synthetic and Natural Pyrrolomycins

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          Abstract

          The emergence of antibiotic resistance is currently considered one of the most important global health problem. The continuous onset of multidrug-resistant Gram-positive and Gram-negative bacterial strains limits the clinical efficacy of most of the marketed antibiotics. Therefore, there is an urgent need for new antibiotics. Pyrrolomycins are a class of biologically active compounds that exhibit a broad spectrum of biological activities, including antibacterial, antifungal, anthelmintic, antiproliferative, insecticidal, and acaricidal activities. In this review we focus on the antibacterial activity and antibiofilm activity of pyrrolomycins against Gram-positive and Gram-negative pathogens. Their efficacy, combined in some cases with a low toxicity, confers to these molecules a great potential for the development of new antimicrobial agents to face the antibiotic crisis.

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          Most cited references 58

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          Antibiotic Discovery: Combatting Bacterial Resistance in Cells and in Biofilm Communities

          Bacterial resistance is a rapidly escalating threat to public health as our arsenal of effective antibiotics dwindles. Therefore, there is an urgent need for new antibiotics. Drug discovery has historically focused on bacteria growing in planktonic cultures. Many antibiotics were originally developed to target individual bacterial cells, being assessed in vitro against microorganisms in a planktonic mode of life. However, towards the end of the 20th century it became clear that many bacteria live as complex communities called biofilms in their natural habitat, and this includes habitats within a human host. The biofilm mode of life provides advantages to microorganisms, such as enhanced resistance towards environmental stresses, including antibiotic challenge. The community level resistance provided by biofilms is distinct from resistance mechanisms that operate at a cellular level, and cannot be overlooked in the development of novel strategies to combat infectious diseases. The review compares mechanisms of antibiotic resistance at cellular and community levels in the light of past and present antibiotic discovery efforts. Future perspectives on novel strategies for treatment of biofilm-related infectious diseases are explored.
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            Antibiotic Adjuvants: Diverse Strategies for Controlling Drug-Resistant Pathogens

            The growing number of bacterial pathogens that are resistant to numerous antibiotics is a cause for concern around the globe. There have been no new broad-spectrum antibiotics developed in the last 40 years, and the drugs we have currently are quickly becoming ineffective. In this article, we explore a range of therapeutic strategies that could be employed in conjunction with antibiotics and may help to prolong the life span of these life-saving drugs. Discussed topics include antiresistance drugs, which are administered to potentiate the effects of current antimicrobials in bacteria where they are no longer (or never were) effective; antivirulence drugs, which are directed against bacterial virulence factors; host-directed therapies, which modulate the host's immune system to facilitate infection clearance; and alternative treatments, which include such therapies as oral rehydration for diarrhea, phage therapy, and probiotics. All of these avenues show promise for the treatment of bacterial infections and should be further investigated to explore their full potential in the face of a postantibiotic era.
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              A new strategy to fight antimicrobial resistance: the revival of old antibiotics

              The increasing prevalence of hospital and community-acquired infections caused by multidrug-resistant (MDR) bacterial pathogens is limiting the options for effective antibiotic therapy. Moreover, this alarming spread of antimicrobial resistance has not been paralleled by the development of novel antimicrobials. Resistance to the scarce new antibiotics is also emerging. In this context, the rational use of older antibiotics could represent an alternative to the treatment of MDR bacterial pathogens. It would help to optimize the armamentarium of antibiotics in the way to preserve new antibiotics and avoid the prescription of molecules known to favor the spread of resistance (i.e., quinolones). Furthermore, in a global economical perspective, this could represent a useful public health orientation knowing that several of these cheapest “forgotten” antibiotics are not available in many countries. We will review here the successful treatment of MDR bacterial infections with the use of old antibiotics and discuss their place in current practice.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                04 December 2015
                December 2015
                : 20
                : 12
                : 21658-21671
                Affiliations
                [1 ]Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche—Sezione di Chimica e Tecnologie Farmaceutiche—Università degli Studi di Palermo, Via Archirafi 32, Palermo 90123, Italy; mariavaleria.raimondi@ 123456unipa.it (M.V.R.); demetrio.raffa@ 123456unipa.it (D.R.); benedetta.maggio@ 123456unipa.it (B.M.); giuseppe.daidone@ 123456unipa.it (G.D.); domenico.schillaci@ 123456unipa.it (D.S.)
                [2 ]IEMEST, Istituto Euromediterraneo di Scienza e Tecnologia, Via Emerico Amari, 123, Palermo 90139, Italy
                Author notes
                [* ]Correspondence: stellamaria.cascioferro@ 123456unipa.it (S.C.); mariagrazia.cusimano@ 123456unipa.it (M.G.C.); Tel.: +39-091-23891920 (S.C.); +39-091-23891914 (M.G.C.)
                Article
                molecules-20-19797
                10.3390/molecules201219797
                6331927
                26690095
                74f51aab-a9bb-43ef-8ec0-9d388a316f7f
                © 2015 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

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