Efflux pumps of Gram-negative bacteria: what they do, how they do it, with what and how to deal with them

Amaral, Leonard; Martins, Ana; Spengler, Gabriella; Molnár, Joséph

doi:10.3389/fphar.2013.00168

Cited by 125 publications

(85 citation statements)

References 93 publications

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“…Studies have shown that targeting the efflux pump system could obviate other resistance mechanisms and reverse multidrug resistance, thus restoring the efficacy of antibiotics [24]. In this study, we observed that susceptibility to ertapenem, doripenem, and tigecycline was increased two-to fourfold in the presence of CCCP (Table 2); we also found that non-susceptibility to ertapenem, doripenem, and tigecycline was completely abolished in 24%, 37.3%, and 48% of the isolates, respectively.…”

Section: Discussionmentioning

confidence: 99%

Role of efflux pumps inhibitor in decreasing antibiotic resistance of Klebsiella pneumoniae in a tertiary hospital in North India

Filgona

Banerjee

Anupurba

2015

J Infect Dev Ctries

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Introduction: The contribution of efflux systems to drug resistance in Enterobacteriaceae is becoming increasingly appreciated. This study phenotypically analyzed the role of efflux mechanisms in resistance to ertapenem, doripenem, and tigecycline among clinical isolates of carbapenem-resistant Klebsiella pneumoniae (CRKP). Methodology: Multidrug-resistant and carbapenem non-susceptible K. pneumoniae isolates were determined by disk diffusion test. Further susceptibility of these isolates to carbapenems, ceftriaxone, cefoperazone, ceftazidime, tigecycline, and colistin was determined by agar dilution assay, and CRKP was identified. While modified Hodge test was used to confirm carbapenemase production, the contribution of efflux mechanisms was determined by a minimum inhibitory concentration (MIC) reduction assay, and typing was done by enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction (PCR). Results: Of the 238 isolates of K. pneumoniae, 174 were multidrug resistant and 74 were CRKP. Forty of the CRKP were positive for carbapenemase production, while 43, 11, and 2 of the CRKP isolates had elevated MIC of ≥ 32 µg/mL for ertapenem, doripenem, and tigecycline, respectively. Twofold or higher MIC reduction to ertapenem, doripenem, and tigecycline was observed in 6, 28, and 27 isolates, respectively; however, non-susceptibility to ertapenem, doripenem and tigecycline was abolished in 2, 11, and 18 K. pneumoniae isolates, respectively. Nine clones of CRKP widely distributed within the hospital were obtained from ERIC PCR.

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Section: Discussionmentioning

confidence: 99%

Role of efflux pumps inhibitor in decreasing antibiotic resistance of Klebsiella pneumoniae in a tertiary hospital in North India

Filgona

Banerjee

Anupurba

2015

J Infect Dev Ctries

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“…This is the special feature of some efflux protein transporter. A case of the last co-operation is that of reserpine and Bmr protein, an individuals from MFS transporters that is responsible for tetracycline efflux in Bacillus subtilis 19 .…”

Section: Efflux Pump Inhibitor Originate From Plantmentioning

confidence: 99%

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2017

IJPSR

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“…One escape strategy is the p odu tio of deg adatio e z es su h as β-lactamases, rendering the antibiotic inactive due to hydrolysis of the β-lactam pharmacophore (Bush 2010;Rawat and Nair 2010). Alternatively, several Gram-negative pathogens overexpress membrane-embedded efflux pumps, which actively transport drugs out of the bacteria (Amaral et al 2014;Blair et al 2014). Therefore, considerable efforts have been made to esto e the a ti a te ial a ti it of β-lactams against Gramnegative pathogens through inhibition of β-lactamases or of efflux pumps.…”

Section: Lessons Learned From Druggable Targets In Bacteriamentioning

confidence: 99%

New Structural Templates for Clinically Validated and Novel Targets in Antimicrobial Drug Research and Development

Klahn

Brönstrup

2016

Current Topics in Microbiology and Immunology

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Abstract:The development of bacterial resistance against current antibiotic drugs necessitates a continuous renewal of the arsenal of efficacious drugs. This imperative has not been met by the output of antibiotic research and development of the past decades for various reasons, including the declining efforts of large pharma companies in this area. Moreover, the majority of novel antibiotics are chemical derivatives of existing structures that represent mostly step innovations, implying that the available chemical space may be exhausted. This review negates this impression by showcasing recent achievements in lead finding and optimization of antibiotics that have novel or unexplored chemical structures. Not surprisingly, many of the novel structural templates like teixobactins, lysocin, griselimycin, or the albicidin/cystobactamid pair were discovered from natural sources. Additional compounds were obtained from the screening of synthetic libraries and chemical synthesis, including the gyrase-inhibiting NTBI s a d spiropyrimidinetrione, the tarocin and targocil inhibitors of wall teichoic acid synthesis, or the boronates and diazabicyclo[3.2

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Efflux pumps of Gram-negative bacteria: what they do, how they do it, with what and how to deal with them

Cited by 125 publications

References 93 publications

Role of efflux pumps inhibitor in decreasing antibiotic resistance of Klebsiella pneumoniae in a tertiary hospital in North India

Role of efflux pumps inhibitor in decreasing antibiotic resistance of Klebsiella pneumoniae in a tertiary hospital in North India

Untitled

New Structural Templates for Clinically Validated and Novel Targets in Antimicrobial Drug Research and Development

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