**3.3 Peptide antibiotics: Plectasin**

Peptides with a CSαβ motif act as primary defenders for their host. Microbe-killing abilities of plant defensins have been demonstrated and transgenic industrial crops have been bred to carry specific defensins to increase their tolerance to plant pathogens. For directly binding to membranes or cell walls, target pathogens do not easily resist peptides with a CSαβ motif as they do to protein-targeting antibiotics. Pathogenic microbes would escape attacking from conventional antibiotics by mutating proteins but it is never easy to change the properties of cell membranes or cell walls. Scaffold of a CSαβ motif could be as a suitable platform for developing peptide antibiotics. Some plant defensins are tested and show activities againt human pathogenic microbes. For example, Rs-AFP2, a defensin isolated from seeds of *Raphanus sativus*, has an inhibitory activity against *Candida albicans* (Landon et al., 2004;Terras et al., 1992;Thomma et al., 2003). Scientists of Novozymes, a Dnaish biotech company, isolated a novel plant defensin, plectasin, with excellent antibiotics ability.

Plectasin is a 40-amino acid residue peptide isolated from saprophytic ascomycete, *Pseudoplectania nigrella*, and might be the first plant defensin with a CSαβ motif isolated from fungus (Mygind et al., 2005). Plectasin expresses anti-bacterial activities against a broad Gram-positive bacteria and has an inhibitory effect at a low concentration of 0.25 μg/ml to growth of *Streptococcus pneumoniae* (Mygind et al., 2005). Plectasin also has a comparable killing rate to *Streptococcus pneumoniae* as do conventional antibiotics (Mygind et al., 2005). *Streptococcus pneumoniae* is a major pathogenic bacteria and the most common cause of hospital/community-acquired pneumonia, bacterial meningitis, bacteremia, sinusitis, septic arthritis, osteomyelitis, peritonitis, and endocarditis (Whitney et al., 2000). Currently, antibiotics are major treatments to patients with infection of *Streptococcus pneumoniae*. In recent years, *Streptococcus pneumoniae* is more and more resistant to antibiotics and the demand for new drugs to cure *Streptococcus pneumoniae* infection is urgent (Baquero et al., 1991;Whitney et al., 2000). Another challenge of theraping *Streptococcus* infection is that *Streptococcus* can be an intracellular pathogen and avoids targeting by the immune system or drugs (Gordon et al., 2000;Talbot et al., 1996). Different from the conventional antibiotics, plectasin can directly act on the cell wall precursor lipid II of *Streptococcus* (Mygind et al., 2005). Studies also showed that plectasin has an intracellular activity against *Streptococcus aureus* both in human monocytes and in mouse peritonitis model without effecting the cells viability or inducing IL-8 production (Brinch et al., 2009;Hara et al., 2008).
