siRNA-mediated gene silencing of MexB from the MexA-MexB-OprM efflux pump in Pseudomonas aeruginosa

Gong, Fengyun; Zhang, Ding-Yu; Zhang, Jiang-Guo; Wang, Lili; Jiang, Qi; Song, Jin Yeong

doi:10.5483/bmbrep.2014.47.4.040

Cited by 16 publications

(9 citation statements)

References 27 publications

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“…siRNAs, compared to similar therapeutic agents, exhibited minimal toxicity and high stability. siRNAs had demonstrated to have a promising modulatory effect on virulence, drug resistance and pathogenesis [63]. The use of siRNA–aptamer conjugates for drug delivery can result in the increase of favorable therapeutic efficacy and safety [24].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic applications of nucleic acid aptamers in microbial infections

et al. 2020

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Today, the treatment of bacterial infections is a major challenge, due to growing rate of multidrug-resistant bacteria, complication of treatment and increased healthcare costs. Moreover, new treatments for bacterial infections are limited. Oligonucleotide aptamers are single stranded DNAs or RNAs with target-selective high-affinity feature, which considered as nucleic acid-based affinity ligands, replacing monoclonal antibodies. The aptamer-based systems have been found to be talented tools in the treatment of microbial infections, regarding their promising anti-biofilm and antimicrobial activities; they can reduce or inhibit the effects of bacterial toxins, and inhibit pathogen invasion to immune cell, as well as they can be used in drug delivery systems. The focus of this review is on the therapeutic applications of aptamers in infections. In this regard, an introduction of infections and related challenges were presented, first. Then, aptamer definition and selection, with a brief history of aptamers development against various pathogens and toxins were reviewed. Diverse strategies of aptamer application in drug delivery, as well as, the effect of aptamers on the immune system, as the main natural agents of human defense against pathogens, were also discussed. Finally, the future trends in clinical applications of this technology were discussed.

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Section: Introductionmentioning

confidence: 99%

Therapeutic applications of nucleic acid aptamers in microbial infections

et al. 2020

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“…SiRNA targeting, therefore, appears to be a novel strategy for treating P. aeruginosa infections. This research provides evidence for studying new antipathogenic drugs targeted to the pathogenicity of P. aeruginosa .…”

Section: Discussionmentioning

confidence: 84%

Effect of small interfering RNA against Paracin 1.7 bacteriocin produced byLactobacillus paracaseiHD1-7

Wang

Gao

et al. 2015

J. Basic Microbiol.

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Lactobacillus paracasei HD1-7 (CCTCCM 205015), isolated from Chinese sauerkraut fermentation broth, contains the bacteriocin Paracin 1.7 which possesses broad-spectrum antibacterial activity. The gene-silencing effect of small interfering RNA (siRNA) is a potential strategy for further understanding the mechanism of production of Paracin 1.7 by L. paracasei HD1-7. In this study, the effect of siRNA on the expression of the most important proteins in the production of Paracin 1.7, sensor kinase (prcK) and response regulator (prcR), was investigated. SiRNA were designed against prcK and prcR, and qRT-PCR was performed to examine the expression of prcK and prcR mRNA. The efficacy of siRNA was determined by comparing the level of antimicrobial activity of the strains. qRT-PCR showed that siRNA-K4 and siRNA-K5 significantly inhibited the expression of prcK mRNA, and siRNA-R4 and siRNA-R6 significantly inhibited the expression of prcR mRNA. The proteins levels and antibacterial activities of mutant strains were lower than the original and control groups, respectively. The results demonstrate that siRNA inhibited both mRNA expression and the production of Paracin 1.7 in L. paracasei HD1-7. Targeting of prcK and prcR with siRNA appears to be a novel strategy for researching the mechanism of Paracin 1.7 production by L. paracasei HD1-7.

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“…They also proved its in vivo efficacy in reducing the bacterial load in a pulmonary infective murine model [ 74 ]. Eliminating the inner membrane component (MexB) of P. aeruginosa by silencing MexB gene expression via siRNA was reported to be effective in reducing its pulmonary infectivity in a mouse model, with decreased viable bacterial counts and pathologic changes in the host lung [ 75 ]. Furthermore, the siRNA-mediated silencing of MexB in P. aeruginosa led to decreased neutrophil recruitment during the late stage of pulmonary infection, thus alleviating the inflammation-related damages to the lung tissues [ 75 ].…”

Section: Emerging Inhaled Antibacterials For Respiratory Bacterial In...mentioning

confidence: 99%

“…Eliminating the inner membrane component (MexB) of P. aeruginosa by silencing MexB gene expression via siRNA was reported to be effective in reducing its pulmonary infectivity in a mouse model, with decreased viable bacterial counts and pathologic changes in the host lung [ 75 ]. Furthermore, the siRNA-mediated silencing of MexB in P. aeruginosa led to decreased neutrophil recruitment during the late stage of pulmonary infection, thus alleviating the inflammation-related damages to the lung tissues [ 75 ]. Pulmonary aerosolized delivery of siRNA targeting TGFβ1 cytokines gene silencing was found to effectively reduce the bacterial load in Mtb-infected mice.…”

Section: Emerging Inhaled Antibacterials For Respiratory Bacterial In...mentioning

confidence: 99%

Pulmonary Delivery of Emerging Antibacterials for Bacterial Lung Infections Treatment

Zheng

Leung

2022

Pharm Res

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Bacterial infections in the respiratory tract are considered as one of the major challenges to the public health worldwide. Pulmonary delivery is an attractive approach in the management of bacterial respiratory infections with a few inhaled antibiotics approved. However, with the rapid emergence of antibiotic-resistant bacteria, it is necessary to develop new/alternative inhaled antibacterial agents in the post-antibiotic era. A pipeline of novel biological antibacterial agents, including antimicrobial peptides, RNAi therapeutics, and bacteriophages, has emerged to combat bacterial infections with excellent performance. In this review, the causal effects of bacterial infections on the related pulmonary infectious diseases will be firstly introduced. This is followed by an overview on the development of emerging antibacterial therapeutics for managing lung bacterial infections through nebulization/inhalation of dried powders. The obstacles and underlying proposals regarding their clinical transformation are also discussed to seek insights for further development. Research on inhaled therapy of these emerging antibacterials are still in the infancy, but the promising progress warrants further attention.

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siRNA-mediated gene silencing of MexB from the MexA-MexB-OprM efflux pump in Pseudomonas aeruginosa

Cited by 16 publications

References 27 publications

Therapeutic applications of nucleic acid aptamers in microbial infections

Therapeutic applications of nucleic acid aptamers in microbial infections

Effect of small interfering RNA against Paracin 1.7 bacteriocin produced byLactobacillus paracaseiHD1-7

Pulmonary Delivery of Emerging Antibacterials for Bacterial Lung Infections Treatment

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