**Abstract**

Actinobacteria have exceptional metabolic diversity and are a rich source of several useful bioactive natural products. Most of these have been derived from Streptomyces, the dominant genus of Actinobacteria. Hence, it is necessary to explore rare actinobacteria for the production of novel bioactive compounds. Amongst the novel metabolites, anti-quorum-sensing agents, which can curb infection without killing pathogens, are gaining importance. Not many studies are targeting anti-quorum-sensing agents from rare actinobacteria and this research area is still in its infancy. This field may lead to novel bioactive compounds that can act against bacterial quorum-sensing systems. These agents can attenuate the virulence of the pathogens without challenging their growth, thereby preventing the emergence of resistant strains and facilitating the elimination of pathogens by the host's immune system. Therefore, this chapter describes the general characteristics and habitats of rare actinobacteria, isolation and cultivation methods, the methods of screening rare actinobacteria for anti-quorum sensing compounds, methods of evaluation of their properties, and future prospects in drug discovery.

**Keywords:** rare actinobacteria, quorum sensing, anti-quorum-sensing compounds, swarming, biofilm

#### **1. Introduction**

Actinobacteria are Gram-positive and high G + C containing bacteria with exceptional metabolic diversity. They are a rich source of several useful bioactive natural products many of which have been reported for their potential roles as antimicrobial, antibacterial, antiviral, anticancer, and antifungal compounds. More than 22,000 bioactive secondary metabolites from microorganisms have been identified and published in the scientific and patent literature, and about half of these compounds are produced by actinobacteria [1]. Currently, approximately 160 antibiotics have been used in human therapy and agriculture, and 100–120 of these compounds, including streptomycin, erythromycin, gentamicin, vancomycin, avermectin, etc., are produced by actinobacteria [2].

Most of these antibiotics in clinical use today have been developed from compounds isolated from Streptomyces, the dominant genus [3]. However, the recent search for the novel compounds from Streptomyces species has often led to the rediscovery of known compounds. Hence, the focus of screening programs has shifted to bioactive compounds from non-Streptomyces genera; also referred to as rare actinobacteria [4].

Recent evidence has demonstrated that rare actinobacteria, might represent a unique source of novel biologically active compounds, and methods designed to isolate and identify a wide variety of such actinobacteria have been developed. These methods include a variety of pre-treatment techniques in combination with appropriately supplementing selective agar media with specific antimicrobial agents.

At present, not more than 50 rare actinobacterial taxa are reported to produce 2500 bioactive compounds [5]. Thus, it is crucial that new groups of rare actinobacteria be pursued as sources of novel pharmaceutically active metabolites. Amongst the novel metabolites, anti-quorum sensing (AQS) agents, which can curb infection without a killing action, are gaining importance. Bacterial cell–cell communication, dubbed quorum sensing, is intricately related to virulence. An associated phenomenon is bacterial swarming which allows the spread of disease and virulence.

The discovery that many pathogenic bacteria employ quorum sensing (QS) to regulate their pathogenicity and virulence factor production makes the QS system an attractive target for antimicrobial therapy. Targeting the pathogenesis instead of killing the organism may provide less selective pressure for the development of resistance. Therefore, it has been suggested that inactivating the QS system in bacteria using QS inhibitors holds great promise for the treatment of infectious diseases. These compounds can attenuate the virulence of the pathogens without challenging their growth, thereby preventing the emergence of resistant strains and facilitating the elimination of pathogens by the host's immune system. Therefore, a search for anti-quorum-sensing agents as attractive alternatives to treat infection has become logical and gathered momentum [6].

Although antimicrobial properties of actinobacteria have been extensively studied, less is known about AQS activities of rare actinobacteria which may be a rich source of active compounds that can act against bacterial quorum-sensing systems.
