Bacteria in Cancer Therapeutics: A Framework for Effective Therapeutic Bacterial Screening and Identification

Abstract

By 2030, the global incidence of cancer is expected to increase by approximately 50%. However, most conventional therapies still lack cancer selectivity, which can have severe unintended side effects on healthy body tissue. Despite being an unconventional and contentious therapy, the last two decades have seen a significant renaissance of bacterium-mediated cancer therapy (BMCT). Although promising, most present-day therapeutic bacterial candidates have not shown satisfactory efficacy, effectiveness, or safety. Furthermore, therapeutic bacterial candidates are available to only a few of the approximately 200 existing cancer types. Excitingly, the recent surge in BMCT has piqued the interest of non-BMCT microbiologists. To help advance these interests, in this paper we reviewed important aspects of cancer, present-day cancer treatments, and historical aspects of BMCT. Here, we provided a four-step framework that can be used in screening and identifying bacteria with cancer therapeutic potential, including those that are uncultivable. Systematic methodologies such as the ones suggested here could prove valuable to new BMCT researchers, including experienced non-BMCT researchers in possession of extensive knowledge and resources of bacterial genomics. Lastly, our analyses highlight the need to establish and standardize quantitative methods that can be used to identify and compare bacteria with important cancer therapeutic traits.

Dual Role of Bacteria in Carcinoma: Stimulation and Inhibition

“…Cancer remains to be one of the highest causes of morbidity and mortality throughout the world; it arises from the growth of malignant cells into masses referred to as tumors; they cause DNA mutations leading to acquisition of epigenetic changes promoting oncogenesis and carcinogenesis with several diseases [1]. Some of these cancers are spreading from their tissue to other parts in the body in a process called metastasis [2,3]. Cancers can be categorized according to their tissue and/or organ of origin; carcinomas, for example, are cancers spreading in tissues covering all the body organs.…”

Exploiting Zebrafish Xenografts for Testing the in vivo Antitumorigenic Activity of Microcin E492 Against Human Colorectal Cancer Cells

“…The use of bacteria or their products against cancer has already been tested at different levels. For instance, a treatment with mixed extracts from Streptococcus pyogenes and Serratia marscensces (currently known as Coley toxins) on unresectable tumors was successfully administrated more than 100 years ago (Karpiński and Adamczak, 2018; reviewed in Baindara et al, 2018;Ashu et al, 2019). Similarly, the study of different bacteriocins and their antineoplasic properties has a long history and has included colicins, pyocins, pediocins, and microcins (reviewed in Lagos, 2007;Cornut et al, 2008).…”

“…Similarly, the study of different bacteriocins and their antineoplasic properties has a long history and has included colicins, pyocins, pediocins, and microcins (reviewed in Lagos, 2007;Cornut et al, 2008). Over the past few years there has been a renewed interest in exploring anticancer properties of other bacteriocins, and among them are laterosporulin10 (Baindara et al, 2017), nisin ZP (Kamarajan et al, 2015), nisin (Joo et al, 2012), plantaricin P1053 (De Giani et al, 2019), and others (reviewed in Kaur and Kaur, 2015;Baindara et al, 2018;Karpiński and Adamczak, 2018;Ashu et al, 2019). Microcins are a class of bacteriocins with a molecular mass of <10 kDa produced by Gram-negative bacteria, principally Enterobactericeae.…”

Targeted Delivery of the Mitochondrial Target Domain of Noxa to Tumor Tissue via Synthetic Secretion System in E. coli

“…Some bacteria have natural anti-tumor traits such as selectivity, cytotoxicity, and immunogenicity specifically against cancer and show persistence inside the body. Additionally, bacteria can carry therapeutic agents to tumors via engineered vectors (Song et al, 2018;Ashu et al, 2019;Duong et al, 2019). Only a few bacterial strains have been selected for cancer therapy with the aforementioned traits, including the genera Salmonella, Lactobacillus, Listeria, Clostridium, and Escherichia coli (Ashu et al, 2019;Duong et al, 2019;Sedighi et al, 2019).…”

“…Additionally, bacteria can carry therapeutic agents to tumors via engineered vectors (Song et al, 2018;Ashu et al, 2019;Duong et al, 2019). Only a few bacterial strains have been selected for cancer therapy with the aforementioned traits, including the genera Salmonella, Lactobacillus, Listeria, Clostridium, and Escherichia coli (Ashu et al, 2019;Duong et al, 2019;Sedighi et al, 2019). Studies have shown that facultative anaerobic bacteria such as E. coli and Salmonella selectively colonize and grow in tumors, especially in hypoxic and necrotic areas, thereby selectively delivering anti-tumor agents to these locations (Yu et al, 2004;Min et al, 2008;Jiang et al, 2010).…”