APPLIED GENETICS AND MOLECULAR BIOTECHNOLOGY An exopolysaccharide produced by the novel halophilic bacterium Halomonas stenophila strain B100 selectively induces apoptosis in human T leukaemia cells Carmen Ruiz-Ruiz & Girish K. Srivastava & Diana Carranza & Juan A. Mata & Inmaculada Llamas & Manuel Santamaría & Emilia Quesada & Ignacio J. Molina Received: 15 June 2010 / Revised: 14 September 2010 / Accepted: 15 September 2010 / Published online: 3 October 2010 # Springer-Verlag 2010 Abstract Microbial exopolysaccharides (EPSs) are highly heterogeneous polymers produced by fungi and bacteria and have recently been attracting considerable attention from biotechnologists because of their potential applica- tions in many fields, including biomedicine. We have screened the antitumoural activity of a panel of sulphated EPSs produced by a newly discovered species of halophilic bacteria. We found that the novel halophilic bacterium Halomonas stenophila strain B100 produced a heteropoly- saccharide that, when oversulphated, exerted antitumoural activity on T cell lines deriving from acute lymphoblastic leukaemia (ALL). Only tumour cells were susceptible to apoptosis induced by the sulphated EPS (B100S), whilst primary T cells were resistant. Moreover, freshly isolated primary cells from the blood of patients with ALL were also susceptible to B100S-induced apoptosis. The newly discovered B100S is therefore the first bacterial EPS that has been demonstrated to exert a potent and selective pro- apoptotic effect on T leukaemia cells, and thus, we propose that the search for new antineoplastic drugs should include the screening of other bacterial EPSs, particularly those isolated from halophiles. Keywords Apoptosis . Exopolysaccharides . T cell leukaemia . Halomonas stenophila B100 . Antitumoural activity Introduction Microbial exopolysaccharides (EPSs) are highly heteroge- neous polymers that contain a wide range of homo- or hetero-carbohydrates as well as organic and inorganic substituents, many of which are strain-specific (reviewed in Sutherland 1985, 1998; Kumar et al. 2007; Nichols et al. 2005). EPSs are secreted by a significant number of bacteria and play a critical role in helping these micro- organisms cope with adverse environmental conditions. Over the last decade, EPSs have been discovered to harbour many hitherto unsuspected biological properties. For instance, some EPSs have been shown in vitro to exert insulinotropic activity, inducing the production of insulin and protecting insulinoma cells from diabetogenic agents (Hwang et al. 2008); a modified EPS secreted by Alteromonas infernus demonstrates weak anticoagulant activity in vitro (Colliec et al. 2001), but strong angiogenic effects (Matou et al. 2005). EPSs also exert antiviral and immunoregulatory activity. At least two EPSs block HSV-2 replication by enhancing the production of pro- inflammatory cytokines (Arena et al. 2006, 2009), whilst some staphylococcal EPSs inhibit lymphocyte proliferation by activating the production of monocyte prostaglandin (Stout et al. 1992). Several fungal EPSs target prostate (Collins et al. 2006; Zhu et al. 2007), lung (Guo et al. 2007) and gastric tumour cells (Kwon and Nam 2006, 2007), C. Ruiz-Ruiz : G. K. Srivastava : D. Carranza : I. J. Molina (*) Institute of Biopathology and Regenerative Medicine, Centre for Biomedical Research, University of Granada Health-Sciences Technology Park, Avda. del Conocimiento s/n, 18100 Armilla-Granada, Spain e-mail: imolina@ugr.es J. A. Mata : I. Llamas : E. Quesada Department of Microbiology, Faculty of Pharmacy, University of Granada, Granada, Spain M. Santamaría Department of Immunology, Faculty of Medicine, University of Cordoba, Cordoba, Spain Appl Microbiol Biotechnol (2011) 89:345–355 DOI 10.1007/s00253-010-2886-7