A<i>Salmonella</i>Typhimurium mutant strain capable of RNAi delivery

Cheng, Xiawei; Zhang, Xiaoxin; Zhou, Yuqiang; Zhang, Chunmei; Zhang, Hua

doi:10.4161/cbt.29185

Cited by 27 publications

(16 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ΔppGpp strain had excellent antitumor activity via its ability to activate the inflammasome (NLRP3, IPAF) and induce the expression of several proinflammatory cytokines (IL-1β, IL-18, and TNF-α) 21 . Deletion of the phoP and phoQ genes did not affect the antitumor activity of Salmonella , while the deletions reduced its virulence in normal tissue 62 . Strains bearing these mutations have been used to produce an excellent vaccine and have recently been used as a delivery system for tumor therapeutics 63–67 .…”

Section: Engineering Of Bacteriamentioning

confidence: 89%

“…Several cytokines, including GM-CSF, IL-12, and IL-18, have entered clinical trials for cancer therapy 136 . Cytokines expressed by tumor-targeting bacteria were delivered specifically to the tumor region, where they augmented the antitumor immune response in the TME 20,29,49,62,137–140 . Intravenous administration of an IL-18-expressing attenuated S .…”

Section: Engineering Of Bacteriamentioning

confidence: 99%

See 1 more Smart Citation

Bacteria-cancer interactions: bacteria-based cancer therapy

et al. 2019

View full text Add to dashboard Cite

Recent advances in cancer therapeutics, such as targeted therapy and immunotherapy, have raised the hope for cures for many cancer types. However, there are still ongoing challenges to the pursuit of novel therapeutic approaches, including high toxicity to normal tissue and cells, difficulties in treating deep tumor tissue, and the possibility of drug resistance in tumor cells. The use of live tumor-targeting bacteria provides a unique therapeutic option that meets these challenges. Compared with most other therapeutics, tumor-targeting bacteria have versatile capabilities for suppressing cancer. Bacteria preferentially accumulate and proliferate within tumors, where they can initiate antitumor immune responses. Bacteria can be further programmed via simple genetic manipulation or sophisticated synthetic bioengineering to produce and deliver anticancer agents based on clinical needs. Therapeutic approaches using live tumor-targeting bacteria can be applied either as a monotherapy or in combination with other anticancer therapies to achieve better clinical outcomes. In this review, we introduce and summarize the potential benefits and challenges of this anticancer approach. We further discuss how live bacteria interact with tumor microenvironments to induce tumor regression. We also provide examples of different methods for engineering bacteria to improve efficacy and safety. Finally, we introduce past and ongoing clinical trials involving tumor-targeting bacteria.

show abstract

Section: Engineering Of Bacteriamentioning

confidence: 89%

Section: Engineering Of Bacteriamentioning

confidence: 99%

Bacteria-cancer interactions: bacteria-based cancer therapy

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Some modifications have been introduced to this strain to enhance safety and/or antitumor phenotypes. For example, Cheng et al [ 15 ] deleted the phoP / phoQ system of VNP20009. The modified strain exhibited lower titers in tumor-free livers and spleens compared with the original VNP20009 strain.…”

Section: Salmonella : Bacterial Tumor-targetingmentioning

confidence: 99%

“…The modified strain exhibited lower titers in tumor-free livers and spleens compared with the original VNP20009 strain. Also, its tumor-targeting ability was significantly enhanced [ 15 ]. Recently, the complete genome of VNP20009 has been sequenced [ 16 ].…”

Section: Salmonella : Bacterial Tumor-targetingmentioning

confidence: 99%

Strains, Mechanism, and Perspective:Salmonella-Based Cancer Therapy

Wang

Kazmierczak

Eisenstark

2016

International Journal of Microbiology

View full text Add to dashboard Cite

Recently, investigation of bacterial-based tumor therapy has regained focus due to progress in molecular, cellular, and microbial biology. Many bacteria such as Salmonella, Listeria, Escherichia, and Clostridium have proved to have tumor targeting and in some cases even tumor-destroying phenotypes. Furthermore, bacterial clinical treatments for cancer have been improved by combination with other therapeutic methods such as chemotherapeutic drugs and radioactive agents. Synthetic biology techniques have also driven the development of new bacterial-based cancer therapies. However, basic questions about the mechanisms of bacterial-mediated tumor targeting and destruction are still being elucidated. In this review, we focus on three tumor-therapeutic Salmonella models, the most intensively studied bacterial genus in this field. One of these Salmonella models is our Salmonella enterica serovar Typhimurium LT2 derived strain CRC2631, engineered to minimize toxicity but maximize tumor-targeting and destruction effects. The other two are VNP20009 and A1-R. We compare the means by which these therapeutic candidate strain models were selected for study, their tumor targeting and tumor destruction phenotypes in vitro and in vivo, and what is currently known about the mechanisms by which they target and destroy tumors.

show abstract

“…baumannii [ 18 , 19 ]. Small interfering RNA (siRNA of 21 to 22 bp) has been used as an important research tool to recognize double-stranded RNA, which may lead to the degradation of target homologous mRNAs upon complementary base pairing [ 20 – 22 ].…”

Section: Introductionmentioning

confidence: 99%

In vitro synergistic effect of amlodipine and imipenem on the expression of the AdeABC efflux pump in multidrug-resistant Acinetobacter baumannii

Zhao

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

IntroductionMultidrug-resistant Acinetobacter baumannii (A. baumannii) has become one of the greatest threats worldwide to the therapeutic management of infections. Our previous research confirmed an in vitro synergistic effect of amlodipine and imipenem against A. baumannii, and this study is designed to understand its mechanism.MethodsSixty-four non-duplicate A. baumannii isolates were collected and tested for antimicrobial susceptibility by the disk diffusion method. PCR amplification and sequencing were used to identify the presence of the adeB, adeE, adeH, adeJ, abeM and abeS efflux pump genes. The minimal inhibitory concentrations of imipenem, imipenem+amlodipine and imipenem+carbonyl cyanide m–chlorophenyl-hydrazone against these isolates were also determined by the broth microdilution method before and after siRNA silencing of the expression of the adeABC efflux pump.ResultsIn this study, the combination of amlodipine with imipenem showed synergistic antimicrobial activity against sixty-four A. baumannii isolates when compared with the activity of imipenem alone (p<0.025). In the multidrug-resistant group, AML was more effective than carbonyl cyanide m–chlorophenyl-hydrazone (p<0.001). The efflux pump genes adeB, adeE, adeH, adeJ, abeM and abeS were detected in 100% (4/64), 75% (48/64), 0% (0/64), 100% (64/64), 96.9% (62/64) and 96.9% (62/64) of the sixty-four A. baumannii isolates, respectively. The expression of the adeABC efflux pump genes in the multidrug-resistant group (5.05±19.25) is clearly higher than in the non-multidrug-resistant group (0.17±0.20), (p = 0.01). A gene silencing test verified that the mRNA expression levels of adeABC were decreased at 12 h and increased at 24 h, while the reversal of imipenem resistance by amlodipine disappeared at 12 h and reappeared at 24 h.ConclusionsThe combination of amlodipine with imipenem exhibits an in vitro synergistic antimicrobial effect on multidrug-resistant A. baumannii, which may be due to the inhibition of the AdeABC efflux pump.

show abstract

ASalmonellaTyphimurium mutant strain capable of RNAi delivery

Cited by 27 publications

References 44 publications

Bacteria-cancer interactions: bacteria-based cancer therapy

Bacteria-cancer interactions: bacteria-based cancer therapy

Strains, Mechanism, and Perspective:Salmonella-Based Cancer Therapy

In vitro synergistic effect of amlodipine and imipenem on the expression of the AdeABC efflux pump in multidrug-resistant Acinetobacter baumannii

Contact Info

Product

Resources

About