Marine bacteria as a source of new antibiotics

Abstract

The pre-antibiotic era was characterised by the lack of antibiotics and hence, the lack of adequate means for the treatment of numerous infectious diseases. The ground-breaking discovery of penicillin and other antibiotics, which came to be widely used in clinical practice, brought great benefit and contributed to the increase of the average human life expectancy from 47 years in 1900 to 74 years (in men) and 80 years (in women) in 2000 in the USA (Lederberg 2000). Furthermore, in 1941 Skinner and Keefer reported a shocking 82 % mortality among 122 consecutive patients who had been treated for Staphylococcus aureus bacteremia before antibiotics were available (Skinner and Keefer 1941), as contrasted to 20-40 % mortality rates being reported in the post-antibiotic era (Mylotte, McDermott et al.1987; Shurland, Zhan et al. 2007). The use of antimicrobials is not limited to clinical applications. Currently antimicrobials, such as, for example, chitosan based products, triclosan and various bacteriocins, are widely used in hand washing products, toothpastes and in the food industry to increase the shelf life of various products (Stephen, Saxton et al. 1990; Waaler, Rolla et al. 1993; Barkvoll and Rolla 1994; Bhargava and Leonard 1996; Gould 1996; Jones, Jampani et al. 2000; Haas, Marie et al. 2005; Galvez 2007; Dutta, Tripathi et al. 2009). By comparison to chemical disinfectants, these natural products are generally less toxic and also provide great advantages, such as biodegradability, biocompatibility as well as chemical and physical versatility (Gould 1996; Dutta, Tripathi et al. 2009). Nevertheless, the use of antibiotics for the treatment of diseases historically remains the main focus of antimicrobial research. Ever since the discovery of penicillin there have been many attempts to find novel antimicrobials due to the inevitability of development of bacterial resistance towards the widely used antibiotics. In the past years much of the effort in that direction was focused on terrestrial sources. Nowadays, more than ever before, the exploration of new and under-explored sources becomes extremely important in the process of finding biologically active compounds (“bioactives”) with novel chemical structures. The majority of antibiotics currently used in clinical practice are of natural product origin (Newman, Cragg et al. 2003; Singh and Barrett 2006; Von Nussbaum, Brands et al. 2006). For example, 70 out of the 90 antibiotics marketed in the years 1982–2002 originated from natural products (Newman, Cragg et al. 2003). Notably, the quinolones or fluoroqinones, one of the most successful classes of synthetic antibiotics, are also based on the structure of the natural product quinine (Demain and Sanchez 2009) (Figure 1). In fact, chemical modifications based on a natural product scaffold is a widely used approach in modifying the chemical and physical properties of the molecule, thus making it useful for a particular pharmacological application (Walters, Murcko et al. 1999; Leeson, Davis et al. 2004). It has been suggested that the success of natural compounds is due to the fact that they have undergone natural selection and, therefore, are best suited to perform their activities (Nisbet and Moore 1997; Muller-Kuhrt 2003; Koehn and Carter 2005). Thus, further research on bioactive natural products may provide a source of new chemical structures that can guide the design of novel chemical compounds (Breinbauer, Vetter et al. 2003; Nicolaou, Chen et al. 2009), as well as reveal yet unknown modes of action (Urizar, Liverman et al. 2002).32 page(s