Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment

Sawant, Shruti S.; Patil, Suyash M.; Gupta, Vivek; Kunda, Nitesh K.

doi:10.3390/ijms21207575

Cited by 52 publications

(31 citation statements)

References 149 publications

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“…Although bacteria were traditionally regarded as carcinogenic, there is now available evidence for their anticancer properties. The role of the microbiome in cancer treatment was proposed as early as 1867, when it was reported that infection with Streptococcus pyogenes caused cancer remission in a patient ( Sawant et al, 2020 ). Bacteria exert anticancer effects via multiple mechanisms including (i) colonizing tumors, (ii) releasing substances, (iii) suppressing nutrients required for tumor metabolism and proliferation, (iv) serving as a vehicle for anticancer drugs delivery, (v) forming biofilms, and (vi) enhancing host immunity ( Soleimanpour et al, 2020 ; Yaghoubi et al, 2020 ).…”

Section: Role Of Bacteria In the Treatment Of Gcmentioning

confidence: 99%

Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment

et al. 2021

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The development of sequencing technology has expanded our knowledge of the human gastric microbiome, which is now known to play a critical role in the maintenance of homeostasis, while alterations in microbial community composition can promote the development of gastric diseases. Recently, carcinogenic effects of gastric microbiome have received increased attention. Gastric cancer (GC) is one of the most common malignancies worldwide with a high mortality rate. Helicobacter pylori is a well-recognized risk factor for GC. More than half of the global population is infected with H. pylori, which can modulate the acidity of the stomach to alter the gastric microbiome profile, leading to H. pylori-associated diseases. Moreover, there is increasing evidence that bacteria other than H. pylori and their metabolites also contribute to gastric carcinogenesis. Therefore, clarifying the contribution of the gastric microbiome to the development and progression of GC can lead to improvements in prevention, diagnosis, and treatment. In this review, we discuss the current state of knowledge regarding changes in the microbial composition of the stomach caused by H. pylori infection, the carcinogenic effects of H. pylori and non-H. pylori bacteria in GC, as well as the potential therapeutic role of gastric microbiome in H. pylori infection and GC.

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Section: Role Of Bacteria In the Treatment Of Gcmentioning

confidence: 99%

Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment

et al. 2021

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“…It was demonstrated different mechanisms of action for individual compounds, from induction of replicative stress to disbalance of cation homeostasis to inhibition of bacterial attachment to the surface. Study demonstrates the potential of drug repurposing for the prevention of bacterial biofilm formation and suggests that also for other bacteria, the activity spectrum of antibiofilm compounds is likely to be broad [42].…”

Section: Resultsmentioning

confidence: 95%

BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review

Ivanenko

2021

Med. Sci. of Ukr.

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Relevance. Treatment of solid tumors and biofilm-derived infections face a common problem: drugs often fail to reach and kill cancer cells and microbial pathogens because of local microenvironment heterogeneities. There are remarkable challenges for current and prospective anticancer and antibiofilm agents to target and maintain activity in the microenvironments where cancer cells and microbial pathogens survive and cause the onset of disease. Bacterial infections in cancer formation will increase in the coming years. Collection of approaches such as ROS modulation in cells, the tumor is promoted by microbe’s inflammation can be a strategy to target cancer and bacteria. Besides that, bacteria may take the advantage of oxygen tension and permissive carbon sources, therefore the tumor microenvironment (TM) becomes a potential refuge for bacteria. It is noteworthy that the relationship between cancer and bacteria is intertwined. Objective: To analyze similarities between biofilm and tumor milieu that is produced against stress conditions and heterogeneous microenvironment for a combination of approaches the bacteriotherapy with chemotherapy which can help in defeating the tumor heterogeneity accompanied with malignancy, drug-resistance, and metastasis. Method: An analytical review of the literature on keywords from the scientometric databases PubMed, Wiley. Results: Bacteria evade antimicrobial treatment is mainly due to persistence that has become dormant during the stationary phase and tolerance. Drug-tolerant persisters and cellular dormancy are crucial in the development of cancer, especially in understanding the development of metastases as a late relapse. Bioﬁlms are formed by groups of cells in diﬀerent states, growing or non-growing and metabolically active or inactive in variable fractions, depending on maturity and on chemical gradients (O2 and nutrients) of the bioﬁlms producing physiological heterogeneity. Heterogeneity in the microenvironment of cancer can be described as a non-cell autonomous driver of cancer cell diversity; in a highly diverse microenvironment, different cellular phenotypes may be selected for or against in different regions of the tumor. Hypoxia, oxidative stress, and inflammation have been identified as positive regulators of metastatic potential, drug resistance, and tumorigenic properties in cancer. It is proven that, Escherichia coli (E. coli) and life-threatening infectious pathogens such as Staphylococcus aureus (SA) and Mycobacterium tuberculosis (Mtb) are noticeably sensitive to alterations in the intracellular oxidative environment. An alternative emerging paradigm is that many cancers may be promoted by commensal microbiota, either by translocation and adherence of microbes to cancer cells or by the distant release of inflammation-activating microbial metabolites. Microbial factors such as F. nucleatum, B. fragilis, and Enterobacteriaceae members may contribute to disease onset in patients with a hereditary form of colorectal cancer (CRC); familial adenomatous polyposis (FAP). These findings are linked with the creation of new biomarkers and therapy for identifying and treating biofilm-associated cancers. Currently, about 20% of neoplasms globally can be caused by infections, with approximately 1.2 million cases annually. Several antineoplastic drugs that exhibited activity against S. mutans, including tamoxifen, doxorubicin, and ponatinib, also possessed activity against other Gram-positive bacteria. Drug repurposing, also known as repositioning, has gained momentum, mostly due to its advantages over de novo drug discovery, including reduced risk to patients due to previously documented clinical trials, lower drug development costs, and faster benchtop-to-clinic transition. Although many bacteria are carcinogens and tumor promoters, some have shown great potential towards cancer therapy. Several species of bacteria have shown an impressive power to penetrate and colonize solid tumors, which has mainly led to neoplasm slower growth and tumor clearance. Different strains of Clostridia, Lactococcus, Bifidobacteria, Shigella, Vibrio, Listeria, Escherichia, and Salmonella have been evaluated against cancer in animal models. Conclusion. Cancer is a multifactorial disease and the use of bacteria for cancer therapy as an immunostimulatory agent or as a vector for carrying the therapeutic cargo is a promising treatment method. Therefore, the world has turned to an alternative solution, which is the use of genetically engineered microorganisms; thus, the use of living bacteria targeting cancerous cells is the unique option to overcome these challenges. Bacterial therapies, whether used alone or combination with chemotherapy, give a positive effect to treat multiple conditions of cancer.

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“…For example, inflammation is an important hallmark of cancer, and the presence of immune cells known as tumor associated macrophages (TAM) is often conducive of tumor growth, metastases and poor outcomes (Gharib et al, 2019;Laoui et al, 2011). TAMs are broadly M2 polarized, and IL-10, IL-12p40 and G-CSF all have been shown to play important roles in impacting the tumor microenvironment through regulation of TAMs (Biswas et al, 2006;Kanemaru et al, 2017;Karagiannidis et al, 2020;Laoui et al, 2011) which could be targeted by the EES in cancer bacteriotherapy (Sawant et al, 2020;Yaghoubi et al, 2019Yaghoubi et al, , 2020bYaghoubi et al, , 2020aZhang et al, 2020). Arthritis represents the other side of immune polarization where homeostasis is driven to a proinflammatory condition (Georgopoulos et al, 1996;Henderson and Pettipher, 1989).…”

Section: Discussionmentioning

confidence: 99%

“…Precedence exists for using bacteria to impact mammalian cell physiology for therapeutic approaches, known as bacteriotherapy, and advances in this field support the development of EES for cellular control. Bacille Calmette-Guerin (BCG, the Mycobacterium bovis strain used as a tuberculosis vaccine) bacteriotherapy has become standard of care for bladder cancer treatment, and many other clinical applications for bacteriotherapy are being devised and tested, including for the treatment of other cancers (Laliani et al, 2020;Sawant et al, 2020;Sedighi et al, 2019;Yaghoubi et al, 2019Yaghoubi et al, , 2020aZhang et al, 2020). Bacterial systems, including EES, represent a potentially powerful means of exploiting prokaryotic versatility for therapeutic purposes.…”

Section: Introductionmentioning

confidence: 99%

Engineered endosymbionts capable of directing mammalian cell gene expression

Madsen

Makela

Greeson

et al. 2021

Preprint

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Modular methods for directing mammalian gene expression would enable advances in tissue regeneration, enhance cell-based therapeutics and improve modulation of immune responses. To address this challenge, engineered endosymbionts (EES) that escape endosomal destruction, reside in the cytoplasm of mammalian cells, and secrete proteins that are transported to the nucleus to control host cell gene expression were developed. Microscopy confirmed that EES escape phagosomes, replicate within the cytoplasm, and can secrete reporter proteins into the cytoplasm that were then transported to the nucleus. Synthetic operons encoding the mammalian transcription factors, Stat-1 and Klf6 or Klf4 and Gata-3 were recombined into the EES genome. Using controlled induction, these EES were shown to direct gene expression in J774A.1 macrophage/monocyte cells and modulate the host cell fates. Expressing mammalian transcription factors from engineered intracellular bacteria as endosymbionts comprises a new tool for directing host cell gene expression for therapeutic and research purposes.

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Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment

Cited by 52 publications

References 149 publications

Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment

Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment

BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review

Engineered endosymbionts capable of directing mammalian cell gene expression

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