In vivo efficacy of doripenem (DRPM) against Pseudomonas aeruginosa in murine chronic respiratory tract infection model

Araki, Nobuko; Yamada, Yasuaki; Kamihira, Shimeru; Yanagihara, Katsunori; Morinaga, Yoshitomo; Yamada, Koichi; Kohno, Shigeru

doi:10.1007/s10156-010-0166-1

Cited by 2 publications

(1 citation statement)

References 18 publications

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“…It has been suggested that the expression of MexA-MexBOprM might be down-regulated when the peripheral environment is permissive to bacterial growth and survival (21). Thus, silencing of MexB gene expression was considered a promising mechanism by which antibiotic sensitivity could be induced.…”

Section: Discussionmentioning

confidence: 99%

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

Gong¹,

Zhang²,

Zhang³

et al. 2014

BMB Reports

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To gain insights into the effect of MexB gene under the short interfering RNA (siRNA), we synthesized 21 bp siRNA duplexes against the MexB gene. RT-PCR was performed to determine whether the siRNA inhibited the expression of MexB mRNA. Changes in antibiotic susceptibility in response to siRNA were measured by the E-test method. The efficacy of siRNAs was determined in a murine model of chronic P. aeruginosa lung infection. MexB-siRNAs inhibited both mRNA expression and the activity of P. aeruginosa in vitro. In vivo, siRNA was effective in reducing the bacterial load in the model of chronic lung infection and the P. aeruginosa-induced pathological changes. MexB-siRNA treatment enhanced the production of inflammatory cytokines in the early infection stage (P ＜ 0.05). Our results suggest that targeting of MexB with siRNA appears to be a novel strategy for treating P. aeruginosa infections. [BMB Reports 2014; 47(4): 203-208]

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Section: Discussionmentioning

confidence: 99%

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

Gong¹,

Zhang²,

Zhang³

et al. 2014

BMB Reports

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Role of MexA-MexB-OprM efflux pump system in chronic Pseudomonas Aeruginosa pulmonary infection in mice

Gong

Wang

Song

et al. 2012

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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In order to investigate the role of the MexA-MexB-OprM efflux pump system in the pathogenesis of Pseudomonas aeruginosa (PA)-induced pulmonary infection, pulmonary infection models were established by intratracheal injection of K767 (wild type), nalB (MexA-MexB-OprM up-regulated mutant), and ΔmexB (knockout) strains, separately. All mice were treated with Meropenem (intraper Δ itoneal injection, 100 mg/kg body weight, twice every day), and strain-related pathology, bacteria count, cytokine level, myeloperoxidase (MPO, indicator of neutrophil recruitment) activity, and macrophage inflammatory protein-2 (MIP-2) expression were evaluated at early (3rd day post-infection) and late (7th and 14th day post-infection) stages of infection. E-test showed that ΔmexB was more significantly Δ sensitive to panipenan (ETP), meropenem (MP) and imipenem (IP) than K767 and nalB strains. There was no significant difference in sensitivity to cefepime (TM) among the three stains. In contrast to the K767 and nalB groups, the ΔmexB group showed decreased bacteria burden over time and less exte Δ nsive pathological change. Additionally, MPO activity and levels of inflammatory cytokines (IL-1b, IL-12, and TNF-α) were increased at the early stage (day 3) and decreased at the later stage (day 14). Serum MIP-2 expression level was steadily increased in all three groups from early to late stages, but significantly higher in ΔmexB group than in K767 and nalB groups ( Δ P<0.05). In conclusion, the MexA-MexB-OprM efflux pump system might play an important role in PA-induced chronic pulmonary infection. High expression of the MexA-MexB-OprM efflux pump could increase antibacterial resistance and promote infection.

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In vivo efficacy of doripenem (DRPM) against Pseudomonas aeruginosa in murine chronic respiratory tract infection model

Cited by 2 publications

References 18 publications

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

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

Role of MexA-MexB-OprM efflux pump system in chronic Pseudomonas Aeruginosa pulmonary infection in mice

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