# Bacteria-Mediated Modulatory Strategies for Colorectal Cancer Treatment
## 2 Bacterotherapy in CRC Treatment
### Mechanisms Used in Bacterotherapy in CRC
#### 2.1.2 Bacterial Peptides
_Exotoxin A_  
Exotoxin A (PE) is also derived from _Pseudomonas aeruginosa_ and represents the most toxic virulence factor of this bacterium [86]. The lethality of PE is based on its adenosine diphosphate (ADP)-ribosylation activity, leading to inactivation of the eukaryotic elongation factor 2 (EF-2) and thus inhibition of host cells protein biosynthesis [86; 87]. These toxic properties have been observed to act as useful anti-cancer agents, since the active domain of PE has been found to specifically target tumor-related antigens [86]. Based on this background, [PERSON] et al. fusioned a mutated PE with the variable regions of a monoclonal antibody directed against the human transferrin receptor to obtain a single-chain immunotoxin, namely HB21(Fv)PE40, in order to analyze its efficacy against murine metastatic CRC cells (KM12L4), and could demonstrate them to be eliminated when systemic administration of HB21(Fv)PE40 was applied [88]. In another study, [PERSON] et al. established another immunotoxin, namely SWA11-ZZ-PE38, which was created by conjugating SWA11 with a modified derivate of PE (PE38) via an Fc-binding ZZ domain from staphylococcal protein A to determine its efficacy against human CRC cells (HCT116, HT-29, COLO320). The in vivo study revealed that SWA11-ZZ-PE38 is able to induce apoptosis in human HT-29, COLO320 and HCT116 cell lines without being cytotoxic in normal tissue. These results seem to be another promising treatment approach for CRC by selectively and effectively targeting CRC cells without causing damage to vital tissue [89]. _Listeriolysin O_  
Listeriolysin O (LLO) is a toxin produced by the facultative anaerobic bacteria _Listeria monocytogenes_ that can enter the cytoplasm of antigen presenting cells, because of LLO's hemolytic activity, penetrating the phagosomal membrane. In phase I and II of clinical trials, _L. monocytogenes_ have been widely utilized as a vaccine vector to stimulate immune responses to fight human cancer [90]. For example, Lm-LLO-E7, a recombational form of _L. monocytogenes_ (rLm) producing the human papilloma virus-16 E7 protein that is expressed in cervical cancer cells fusioned with LLO, has been demonstrated as being capable of inducing a potent anti-tumor response [91]. In another study, LLO from _L. monocytogenes_ was fusioned to a HER2/neu oncogene expressing protein (ADXS31-142) that has been shown to exhibit anti-tumor effects in a variety of human carcinomas, including the Colo205 CRC cell line [92]. _B: Non-Ribosomal Peptides_  
Non-ribosomal peptides represent another class of peptides that can be synthesized by bacteria, fungi as well as cyanobacteria and represent another kind of metabolite displaying cancer protective properties, as well as against CRC, such as, for example, Lucentamycins, Arenamides, Ohmyungsamycins, Mixirins or Urukthapelstatin A, which are described in the following sections (Table 2) [52]. _Lucentamycin_  
Lucentamycin (A-D)(3-methyl-4-ethylideneproline containing peptides) are isolated from the bacterial strain _Nocardiopsis lucentensis_ and represent another type of peptide showing cytotoxicity against HCT-116 colon carcinoma cells [99]. However, not many studies investigating lucentamycin's interactions with cancer, especially CRC cells, have been carried out yet.