Reserpine Is the New Addition into the Repertoire of AcrB Efflux Pump Inhibitors

Shaheen, Aqsa; Afridi, Waqar Ahmed; Mahboob, Sadia; Sana, Maryam; Zeeshan, Nadia; Ismat, Fouzia; Mirza, Osman; Iqbal, Mazhar; Rahman, Mahmuder

doi:10.1134/s0026893319040113

Cited by 20 publications

(18 citation statements)

References 43 publications

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“…The combination of reserpine with ciprofloxacin resulted in enhanced drug-induced growth inhibition of E. coli C41(DE3) cells expressing AcrB protein transporter. This study supported the role of reserpine in modulating AcrB activity and potentiating the ciprofloxacin action against host cells [ 93 ]. Interestingly, Tariq et al reported the EPI activity of reserpine against the efflux transporter STY4874, belonging to MFS, overexpressed in pMR4/ E. coli .…”

Section: Alkaloidssupporting

confidence: 81%

Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections

et al. 2020

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Antibiotic resistance is now considered a worldwide problem that puts public health at risk. The onset of bacterial strains resistant to conventional antibiotics and the scarcity of new drugs have prompted scientific research to re-evaluate natural products as molecules with high biological and chemical potential. A class of natural compounds of significant importance is represented by alkaloids derived from higher plants. In this review, we have collected data obtained from various research groups on the antimicrobial activities of these alkaloids against conventional antibiotic-resistant strains. In addition, the structure–function relationship was described and commented on, highlighting the high potential of alkaloids as antimicrobials.

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Section: Alkaloidssupporting

confidence: 81%

Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections

et al. 2020

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“…It is noteworthy that the controls also showed a better predicted affinity towards the AcrB portion. Recently, reserpine was described as an AcrB inhibitor [28], and the docking study suggested the SBS as one of the binding sites for reserpine. Taking into account the docking results, we chose to study the efflux modulation of a model without the AcrA portion, as this was predicted to be the portion to which the compounds presented the least affinity.…”

Section: Docking Resultsmentioning

confidence: 99%

Xanthones Active against Multidrug Resistance and Virulence Mechanisms of Bacteria

et al. 2021

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The emergence of multidrug and extensively drug-resistant pathogenic bacteria able to resist to the action of a wide range of antibiotics is becoming a growing problem for public health. The search for new compounds with the potential to help in the reversion of bacterial resistance plays an important role in current medicinal chemistry research. Under this scope, bacterial efflux pumps are responsible for the efflux of antimicrobials, and their inhibition could reverse resistance. In this study, the multidrug resistance reversing activity of a series of xanthones was investigated. Firstly, docking studies were performed in the AcrAB-TolC efflux pump and in a homology model of the NorA pump. Then, the effects of twenty xanthone derivatives on bacterial growth were evaluated in Staphylococcus aureus 272123 and in the acrA gene-inactivated mutant Salmonella enterica serovar Typhimurium SL1344 (SE03). Their efflux pump inhibitory properties were assessed using real-time fluorimetry. Assays concerning the activity of these compounds towards the inhibition of biofilm formation and quorum sensing have also been performed. Results showed that a halogenated phenylmethanamine xanthone derivative displayed an interesting profile, as far as efflux pump inhibition and biofilm formation were concerned. To the best of our knowledge, this is the first report of xanthones as potential efflux pump inhibitors.

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“…Thus, compounds inhibiting efflux pumps are expected to influence internal concentrations of substances such as antibiotics, and combined use of EIs with antimicrobials might increase bacterial susceptibility [ 51 , 55 , 56 , 57 ]. CCCP, reserpine or valinomycin inhibit ABC, DMT, MATE, MFS and/or RND [ 51 , 55 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ], which are the main conserved families of bacterial efflux pumps [ 51 , 65 , 66 , 67 ]. As the antimicrobial activity of compound IV derivatives is not greatly affected by those EIs, these IV -related antimicrobials do not seem to be substrates of the most common types of bacterial efflux pumps, which adds to their potential to bypass intrinsic resistance mechanisms of H. pylori .…”

Section: Discussionmentioning

confidence: 99%

Selective Targeting of Human and Animal Pathogens of the Helicobacter Genus by Flavodoxin Inhibitors: Efficacy, Synergy, Resistance and Mechanistic Studies

Salillas

Galano‐Frutos

Mahía

et al. 2021

IJMS

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Antimicrobial resistant (AMR) bacteria constitute a global health concern. Helicobacter pylori is a Gram-negative bacterium that infects about half of the human population and is a major cause of peptic ulcer disease and gastric cancer. Increasing resistance to triple and quadruple H. pylori eradication therapies poses great challenges and urges the development of novel, ideally narrow spectrum, antimicrobials targeting H. pylori. Here, we describe the antimicrobial spectrum of a family of nitrobenzoxadiazol-based antimicrobials initially discovered as inhibitors of flavodoxin: an essential H. pylori protein. Two groups of inhibitors are described. One group is formed by narrow-spectrum compounds, highly specific for H. pylori, but ineffective against enterohepatic Helicobacter species and other Gram-negative or Gram-positive bacteria. The second group includes extended-spectrum antimicrobials additionally targeting Gram-positive bacteria, the Gram-negative Campylobacter jejuni, and most Helicobacter species, but not affecting other Gram-negative pathogens. To identify the binding site of the inhibitors in the flavodoxin structure, several H. pylori-flavodoxin variants have been engineered and tested using isothermal titration calorimetry. An initial study of the inhibitors capacity to generate resistances and of their synergism with antimicrobials commonly used in H. pylori eradication therapies is described. The narrow-spectrum inhibitors, which are expected to affect the microbiota less dramatically than current antimicrobial drugs, offer an opportunity to develop new and specific H. pylori eradication combinations to deal with AMR in H. pylori. On the other hand, the extended-spectrum inhibitors constitute a new family of promising antimicrobials, with a potential use against AMR Gram-positive bacterial pathogens.

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Reserpine Is the New Addition into the Repertoire of AcrB Efflux Pump Inhibitors

Cited by 20 publications

References 43 publications

Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections

Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections

Xanthones Active against Multidrug Resistance and Virulence Mechanisms of Bacteria

Selective Targeting of Human and Animal Pathogens of the Helicobacter Genus by Flavodoxin Inhibitors: Efficacy, Synergy, Resistance and Mechanistic Studies

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