Background As multidrug-resistant (MDR) pathogens continue to emerge, there is a substantial amount of pressure to identify new drug candidates. Carboxyl polyethers, also referred to as polyether antibiotics, are a unique class of compounds with outstanding potency against a variety of critical infectious disease targets including protozoa, bacteria and viruses. The characteristics of these molecules that are of key interest are their selectivity and high potency against several MDR etiological agents. Objective Although many studies have been published about carboxyl polyether antibiotics, there are no recent reviews of this class of drugs. The purpose of this review is to provide the reader with an overview of the spectrum of activity of polyether antibiotics, their mechanism of action, toxicity and potential as drug candidates to combat drug-resistant infectious diseases. Conclusion Polyether ionophores show a high degree of promise for the potential control of drug-resistant bacterial and parasitic infections. Despite the long history of use of this class of drugs, very limited medicinal chemistry and drug optimization studies have been reported, thus leaving the door open to these opportunities in the future. Scifinder and PubMed were the main search engines used to locate articles relevant to the topic presented in the present review. Keywords used in our search were specific names of each of the 88 compounds presented in the review as well as more general terms such as polyethers, ionophores, carboxylic polyethers and polyether antibiotics.

The antimalarial guided fractionation of the culture of marine Streptomyces sp. strain H668 led to the isolation of a new polyether metabolite. The structure was determined by comprehensive NMR and MS assignments. This new metabolite showed in vitro antimalarial activity against both the chloroquine-susceptible (D6) and -resistant (W2) clones of Plasmodium falciparum, without cytotoxicity to normal cells (Vero) making it a promising first lead from this marine bacterium.Malaria is a tropical infection caused by four different species of protozoa from the genus Plasmodium transmitted to humans by the Anopheles mosquitoes. During past decades, chloroquine and other aminoquinolines have been utilized as frontline antimalarial agents. However, an increase in drug resistance in Plasmodium falciparum has made it essential to develop new chemotherapeutic agents in addition to combination therapies utilizing available antimalarial drugs with different modes of action. 1 Recently some specific polyether antibiotics have been reported to have potent antimalarial activity. 2-5 K-41, a carboxylic acid containing polyether antibiotic produced from Streptomyces hygroscopicus. K-41, has been reported to exhibit nanomolar in vitro antimalarial activity against Plasmodium falciparum strains K1 (drug resistant) and FCR3 (drug sensitive). 3 Furthermore, it showed high selectivity in vivo against both P. berghei strain N and P. yoelii strain NS infected mice, when administered orally. 3 Several polyethers from this class, such as lonomycin A, nigericin, and monensin have been identified as potential antimalarial agents due to their highly potent and selective activity. 4,5 These compounds classified as ionophores owe their potential activity to interact with ions (cations). A unique structural feature 4,5,11 is that they possess a polycyclic alkyl backbone which confers lipophilic character to these compounds and a terminal carboxyl group which plays an important role in the formation of oxygen rich internal cavity which is capable of binding metal ions. 11 Though rich in oxygen atoms, these molecules are lipophylic in nature. Since the parasite infected cell membrane is vulnerable to binding with lipophilic compounds, © 2008 Elsevier Ltd. All rights reserved. *Corresponding author. Tel.: +1-662-915-5730; fax: +1-662-915-5730; e-mail: mthamann@olemiss.edu. *Corresponding author. Tel.: +0-000-000-0000 ; fax: +0-000-000-0000 ; e-mail: hillr@umbi.umd.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. An antimalarial screening effort of marine microorganisms from Hawaiian sediments yie...

An innovative approach to Post-Harvest Processing (PHP) of oysters is introduced focusing on the effects of supercritical carbon dioxide (scCO 2 ) on bacterial contaminants trapped in the digestive system of oysters. Oysters were exposed to scCO 2 under two conditions: (1) 100 bar and 37 °C for 30 minutes and (2) 172 bar and 60 °C for 60 minutes. Using FDA standard guidelines for food analysis, variations in the Aerobic Plate Count (APC) was assessed. It was established that exposing oysters to CO 2 at 100 bar and 37 °C for 30 minutes and at 172 bar and 60°C for 60 minutes induced 2-log and 3-log reductions in the APC respectively. The decrease in the microbial load as a result of treatment with scCO 2 was found to be significant (P=0.002). A release of adductor muscles from the shell was noted in oysters treated at 172 bar and 60 °C for 60 minutes; this was not the case for oysters treated at 100 bar and 37 °C for 30 minutes. A blind study allowing sensory analysis of treated vs. untreated oysters was also completed and no significant change in the physical appearance, smell, or texture was recorded. In this paper, we also report the effect of scCO 2 on several bacterial isolates, including a referenced ATCC strain of a non pathogenic Vibrio (V. fisherii) as well as several other bacterial isolates cultured from oyster' tissues and found to share biochemical features common to pathogenic Vibrio strains. A complete inactivation (minimum 7-log reduction) was achieved with these latter bacterial isolates. A 6-log reduction was observed with V. fisherii.

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