**1. Introduction**

360 Antimicrobial Agents

Zaidan, M.R., R.A. Noor, A.R. Badrul *et al*., 2005. *In vitro* screening of five local medicinal

Zakaria, H.M., J.M. Mainen, J.M. Pax., C.K. Modest, S.O.N. Ramadhani, 2007. Antimicrobial

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*Asian Nat Prod Res*., 10: 939-943.

plants for antibacterial activity using disc diffusion method. *Trop Biomed*., 22: 165-

activity and brine shrimp toxicity of extracts of *Terminalia brownii* roots and stem.

labdane diterpenoid glycosides from the aerial parts of *Andrographis paniculata*. *J* 

Since ancient times, the mushrooms have been prized as food as well as source for drugs, giving rise to an increasing interest today ("functional food"). Number of macrofungi is of a medicinal importance and represents an unlimited source of secondary metabolites of high medicinal value while a large number of biologically active molecules are identified in many species of macrofungi throughout the world (Wasser & Weis, 1999; Kitzberger et al., 2007; Barros et al., 2007; Turkoglu et al., 2007; Kim et al., 2008; 2007; Wasser, 2011). In addition, of importance is the amount of produced substances namely, they must be simple for the manufacturing (industrial synthesis) or there must be enough raw material for extraction of active molecules. Such molecules, if chemical groups responsible for biological activity are known, should serve as basic compounds for the synthesis of new molecules.

Lignicolous macrofungi express significant biological effects, including antibacterial activity (Hur et al., 2004; Ishikawa et al., 2005; Kalyoncu et al., 2010) and their secondary metabolites can be easily extracted and identified. It has been found that secondary metabolites are very divergent in structure and play no essential role in their growth and reproduction, but probably have a function in biochemical evolution of a species ensuring its survival (Engler et al., 1998). The presence of these compounds in macrofungi is genetically determined, but also varies as a function of ecological factors and the growth stage of these organisms (Puttaraju et al., 2006). The fungal metabolites of fruiting bodies frequently differ from those of mycelia of submerged cultures or fermentation broth. Moreover, biogenetic pathways are rather dependent on their habitats or geographic origin. The chemical composition of fungal species significantly relies on the strains and sites (substrates) of the fruiting body production. The level of phenolic compounds seems to be very much dependent on the location and stress conditions (Kim et al., 2008). With regard to this, more geographical regions and more habitats should be analyzed in the future.

A great potential of these fungi is found in their use as dietary supplements, regardless active principle. A number of products derived from mushrooms that are sold in the market is untested and of suspicious quality. Since the natural style of life become more and more popular around the world, what means return to the organic, natural food and medicines, many people lack a critical attitude to the so-called ecological products. It would therefore be important to develop food suplements and medicines based on natural resources, but with the necessary scientific confirmation of values of such products.

Antibacterial Agents from Lignicolous Macrofungi 363

frequently used antibiotics increased, resulting in low respond to the antibiotic treatment. The existance of multidrug-resistant diseases, once felt to be under control, increased as well, tuberculosis, penicillin-resistant pneumonia, resistant malaria (the cause of death of 1.1 million people in 1998), resistant strains of gonorrhea or dysentery caused by Shigella and

Public concern about infection has been expanded, resulting in a greater public use of a variety of antibacterial agents designed to remove disease-causing organisms from external surfaces before they can enter the body. Today, antibacterials may also be impregnated into sponges, cutting boards, carpeting, and children's toys. However, if used too frequently and indiscriminately, certain antibacterial agents, those that leave trace chemical residues and that target particular processes in the life cycle of bacteria, may select for resistant strains

Furthermore, no new class of antibacterial substances has been developed to combat infectious diseases since 1970 (WHO, 2000). It is therefore necessary to find some new compounds to fight against these resistant microorganisms. Then starts the parallel struggle against antibiotic resistance exhibited in the continuous screening of new natural resources of undiscovered antibiotics from the nature. In this manner, the potential of mushrooms have a great advantage, even in comparison to the bacteria. Nowadays it is much more complicated to find new pharmaceutical active substances by chemical synthesis than from the existing and unexplored natural resources. Screenings of biological activities have made great progress in exploring the rich unlimited and undiscovered natural products in order to use it for production of pharmaceutical and agrochemical products (Anke, 1989). Many organisms were studied as potentially new resources of undiscovered bioactive components, among which fungi from the phylum Basidiomycota gave the promising results. In the forties, the pioneers in such research were Anchel, Hervey, Wilkins et al. and Florey et al. 1949, who tested extracts derived from fruiting bodies and mycelia cultures of more then 2000 species, resulting in isolation of a tricyclic diterpene antibiotic (pleuromutilin from *Pleurotus mutilus*). During nineties of the last century many new structures and biological activities were detected (Anke, 1989). Since then, numerous studies have been performed. Today we are witnessing very important struggle not only against microorganisms but also against other human

Salmonella (2.2 million deaths in 1998).

diseases such as cancer, viral and other diseases.

**1.4 Antimicrobial substances - Antibiotics from fungi and macrofungi** 

the most prominent cause of chronic hepatitis that leads to tumor malignancy.

Microbial metabolites and their derivatives play an important role in the development of medicines. The use of these metabolites has grown extensively over the past century, starting with the Fleming's discovery of penicillin (1924), originally from *Penicillium notatum* filamentous micro-fungus, via Brotzu's discovery of cephalosporins from another fungus, mold *Cephalosporium acremonium* (*Acremonium chrysogenum* now), until today when the Japanese clinics use 30 penicillin derivatives and about 49 derivatives of cephalosporin. Although the metabolites originating from fungi were the main targets of antimicrobial screening, these studies were interrupted for a short time by Waksman's discovery of streptomycin (1945) originating from Actinomycetes. It is believed that the cause of the break helped by the fact that fungi often produce mycotoxins with pronounced cytotoxicity in humans and animals, and one example is the aflatoxin from the mold *Aspergillus flavus*,

(http://www.tufts.edu/med/apua/about\_issue/agents.shtml).
