Bacterial Proteinaceous Compounds With Multiple Activities Toward Cancers and Microbial Infection

Abstract

In recent decades, cancer and multidrug resistance have become a worldwide problem, resulting in high morbidity and mortality. Some infectious agents like Streptococcus pneumoniae, Stomatococcus mucilaginous, Staphylococcus spp., E. coli. Klebsiella spp., Pseudomonas aeruginosa, Candida spp., Helicobacter pylori, hepatitis B and C, and human papillomaviruses (HPV) have been associated with the development of cancer. Chemotherapy, radiotherapy and antibiotics are the conventional treatment for cancer and infectious disease. This treatment causes damage in healthy cells and tissues, and usually triggers systemic side-effects, as well as drug resistance. Therefore, the search for new treatments is urgent, in order to improve efficacy and also reduce side-effects. Proteins and peptides originating from bacteria can thus be a promising alternative to conventional treatments used nowadays against cancer and infectious disease. These molecules have demonstrated specific activity against cancer cells and bacterial infection; indeed, proteins and peptides can be considered as future antimicrobial and anticancer drugs. In this context, this review will focus on the desirable characteristics of proteins and peptides from bacterial sources that demonstrated activity against microbial infections and cancer, as well as their efficacy in vitro and in vivo.

Keywords: anticancer; antimicrobial; bacteriocin; peptides; protein.

FIGURE 1

An overview of different structures of bacteriocins, proteins (A) and peptides (B) with dual anticancer and antimicrobial activity. All of these structures are available on the PDB.

FIGURE 2

Distribution of described anticancer and antimicrobial proteins and peptides.

FIGURE 3

Different mechanisms of action of proteins and peptides with anticancer and antibacterial activity. (A) This section represents the protein and peptide interaction with the carpet model, barrel-stave model, toroidal pore, disorder toroidal pore, non-bilayer intermediate and membrane thinning/thickening, which are mechanisms that act in the conformation of the external membrane (I), target the inhibition of phospholipase, lipid II and LPS permeabilization. In the inner membrane, these mechanisms act in DNA synthesis (II) and inhibition of fold protein (III). (B) This section represents the action of proteins and peptides interaction the other mechanisms described above, such as anion carrier, charged lipid clustering, electroporation, non-lytic membrane depolarization, and oxidized lipid targeting, act in the destabilization of membrane components (I): in addition, they act in the inner membrane by interrupting DNA (II), RNA(III), and protein syntheses (IV) and (V). All these mechanisms can cause bacterial death and, in cancer cells, can cause disruption of membrane, apoptosis, necrosis, and control of angiogenesis. The model described in (A) and (B) acting in bacteria and cancer cells.