The anti-cancerous drug doxorubicin decreases the c-di-GMP content in Pseudomonas aeruginosa but promotes biofilm formation

Groizeleau, Julie; Rybtke, Morten; Andersen, Jens Bo; Berthelsen, Jens; Liu, Yang; Yang, Liang; Nielsen, Thomas E.; Kaever, Volkhard; Givskov, Michael; Tolker‐Nielsen, Tim

doi:10.1099/mic.0.000354

Cited by 21 publications

(15 citation statements)

References 72 publications

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“…The attenuation of bacterial c-di-GMP signaling resulted in greater clearance of the infection (115). However, a pharmacologic approach using doxorubicin, which was identified to be a potent c-di-GMP inhibitor in a large screen, paradoxically caused an increase in biofilm size (116). Therefore, further studies are needed to ascertain whether suppression of c-di-GMP signaling represents a promising potential therapy.…”

Section: Inhibition Of C-di-gmp Bacterial Signalingmentioning

confidence: 99%

Pseudomonas aeruginosaBiofilms: Host Response and Clinical Implications in Lung Infections

Maurice

Bedi

Sadikot

2018

Am J Respir Cell Mol Biol

291

195

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Pseudomonas aeruginosa is a major health challenge that causes recalcitrant multidrug-resistant infections, especially in immunocompromised and hospitalized patients. P. aeruginosa is an important cause of nosocomial and ventilator-associated pneumonia characterized by high prevalence and fatality rates. P. aeruginosa also causes chronic lung infections in individuals with cystic fibrosis. Multidrug- and totally drug-resistant strains of P. aeruginosa are increasing threats that contribute to high mortality in these patients. The pathogenesis of many P. aeruginosa infections depends on its ability to form biofilms, structured bacterial communities that can coat mucosal surfaces or invasive devices. These biofilms make conditions more favorable for bacterial persistence, as embedded bacteria are inherently more difficult to eradicate than planktonic bacteria. The molecular mechanisms that underlie P. aeruginosa biofilm pathogenesis and the host response to P. aeruginosa biofilms remain to be fully defined. However, it is known that biofilms offer protection from the host immune response and are also extremely recalcitrant to antimicrobial therapy. Therefore, development of novel therapeutic strategies specifically aimed at biofilms is urgently needed. Here, we review the host response, key clinical implications of P. aeruginosa biofilms, and novel therapeutic approaches to treat biofilms relevant to lung infections. Greater understanding of P. aeruginosa biofilms will elucidate novel avenues to improve outcomes for P. aeruginosa pulmonary infections.

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Section: Inhibition Of C-di-gmp Bacterial Signalingmentioning

confidence: 99%

Pseudomonas aeruginosaBiofilms: Host Response and Clinical Implications in Lung Infections

Maurice

Bedi

Sadikot

2018

Am J Respir Cell Mol Biol

291

195

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“…Pyocyanin, a toxin produced and secreted by P. aeruginosa, promotes cancer cell death and can also inhibit lymphocyte activity 7 , 47 . Studies have shown that P. aeruginosa- secreted factors enhance the ability of doxorubicin to inhibit tumor proliferation 48 . Transcriptomic analysis of doxorubicin effects on P. aeruginosa indicate doxorubicin increased pqsH gene expression, which is a FAD-dependent monooxygenase required for the production of the Pseudomonas quinolone signal (PQS) 7 .…”

Section: Therapeutic Response By Microbial In Breast Cancermentioning

confidence: 99%

Tumor-related Microbiome in the Breast Microenvironment and Breast Cancer

Wang¹,

Sun²,

Xu³

2021

J. Cancer

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Despite the significant progress in diagnosis and treatment over the past years in the understanding of breast cancer pathophysiology, it remains one of the leading causes of mortality worldwide among females. Novel technologies are needed to improve better diagnostic and therapeutic approaches, and to better understand the role of tumor-environment microbiome players involved in the progression of this disease. The gut environment is enriched with over 100 trillion microorganisms, which participate in metabolic diseases, obesity, and inflammation, and influence the response to therapy. In addition to the direct metabolic effects of the gut microbiome, accumulating evidence has revealed that a microbiome also exists in the breast and in breast cancer tissue. This microbiome enriched in the breast environment and the tumor microenvironment may modulate effects potentially associated with carcinogenesis and therapeutic interventions in breast tissue, which to date have not been properly acknowledged. Herein, we review the most recent works associated with the population dynamics of breast microbes and explore the significance of the microbiome on diagnosis, tumor development, response to chemotherapy, endocrine therapy, and immunotherapy. To overcome the low reproducibility of evaluations of tumor-related microbiome, sequencing technical escalation and machine deep learning algorithms may be valid for standardization of assessment for breast-related microbiome and their applications as powerful biomarkers for prognosis and predictive response in the future.

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“…Anti-cancer agents induced and promoted biofilm formation in Pseudomonas aeruginosa during cancer treatment with hydroxyurea and doxorubicin [ 114 ]. To escape the drug attack, the bacteria growing on the cancer cells are triggered by an SOS response, which is an inducible DNA damage repair system [ 115 ].…”

Section: Mechanism Of Tumor Suppressionmentioning

confidence: 99%

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

Sawant

Patil

Gupta

et al. 2020

IJMS

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Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.

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The anti-cancerous drug doxorubicin decreases the c-di-GMP content in Pseudomonas aeruginosa but promotes biofilm formation

Cited by 21 publications

References 72 publications

Pseudomonas aeruginosaBiofilms: Host Response and Clinical Implications in Lung Infections

Pseudomonas aeruginosaBiofilms: Host Response and Clinical Implications in Lung Infections

Tumor-related Microbiome in the Breast Microenvironment and Breast Cancer

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

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