Bacterial resistance to antibiotics: Active efflux and reduced uptake

Kumar, Ayush; Schweizer, Herbert P.

doi:10.1016/j.addr.2005.04.004

Cited by 417 publications

(295 citation statements)

References 278 publications

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“…Many mechanisms are involved in the process of antibiotic resistances which mainly include enzymatic degradation and modification of the antibiotic agent [2], modification of the target site of the drug [3], and active reflux and reduced uptake of the drug [4]. Pseudomonas aeruginosa is an opportunistic human pathogen Gram negative bacterium which is responsible for infections such as blood stream nosocomial infections, especially in immunocompromised patients and the elderly population of industrial societies [5].…”

Section: Introductionmentioning

confidence: 99%

The combination effects of trivalent gold ions and gold nanoparticles with different antibiotics against resistant Pseudomonas aeruginosa

et al. 2012

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Despite much success in drug design and development, Pseudomonas aeruginosa is still considered as one of the most problematic bacteria due to its ability to develop mutational resistance against a variety of antibiotics. In search for new strategies to enhance antibacterial activity of antibiotics, in this work, the combination effect of gold materials including trivalent gold ions (Au 3+ ) and gold nanoparticles (Au NPs) with 14 different antibiotics was investigated against the clinical isolates of P. aeruginosa, Staphylococcus aureus and Escherichia coli. Disk diffusion assay was carried out, and test strains were treated with the sub-inhibitory contents of gold nanomaterial. Results showed that Au NPs did not increase the antibacterial effect of antibiotics at tested concentration (40 μg/disc). However, the susceptibility of resistant P. aeruginosa increased in the presence of Au 3+ and methicillin, erythromycin, vancomycin, penicillin G, clindamycin and nalidixic acid, up to 147 %. As an individual experiment, the same group of antibiotics was tested for their activity against clinical isolates of S. aureus, E. coli and a different resistant strain of P. aeruginosa in the presence of sub-inhibitory contents of Au 3+, where Au 3+ increased the susceptibility of test strains to methicillin, erythromycin, vancomycin, penicillin G, clindamycin and nalidixic acid. Our finding suggested that using the combination of sub-inhibitory concentrations of Au 3+ and methicillin, erythromycin, nalidixic acid or vancomycin may be a promising new strategy for the treatment of highly resistant P. aeruginosa infections.

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Section: Introductionmentioning

confidence: 99%

The combination effects of trivalent gold ions and gold nanoparticles with different antibiotics against resistant Pseudomonas aeruginosa

et al. 2012

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“…A phenotype (or species) is 70 defined by its relation to an antibiotic: it can produce, can be resistant to, or can 71 be sensitive to the given antibiotic. Naturally, a species producing an antibiotic 72 is also resistant to it, where the resistance is carried out either by removing antibiotic molecules from the cell via efflux mechanisms, or by neutralizing these 74 molecules within the cell (Kumar and Schweizer, 2005). Accordingly, a cell 75 producing an antibiotic l (P l ) is also intrinsically resistant (R l ) to this antibiotic.…”

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confidence: 99%

Analysis of stability to cheaters in models of antibiotic degrading microbial communities

Szilágyi

Boza

Scheuring

2017

Journal of Theoretical Biology

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Antibiotic resistance carried out by antibiotic degradation has been suggested recently as a new mechanism to maintain coexistence of microbial species competing on a single limiting resource, even in well-mixed homogeneous environments. Species diversity and community stability, however, critically depend on resistance against social cheaters, mutants that do not invest in production, but still enjoy the benefits provided by others. Here we investigate how different mutant cheaters affect the stability of antibiotic producing and degrading microbial communities. We consider two cheater types, production and degradation cheaters. We generalize the mixed inhibition-zone and chemostat models introduced previously (Kelsic et al., 2015) to study the population dynamics of microbial communities in well-mixed environment, and analyze the invasion of different cheaters in these models. We show that production cheaters, mutants that cease producing antibiotics, always destroy coexistence whenever there is a cost of producing these antibiotics. Degradation cheaters, mutants that loose their function of producing extracellular antibiotic degrading molecules, induce community collapse only if the cost of producing the degradation factors is above * Corresponding author Email address: istvan.scheuring@ttk.elte.hu (István Scheuring)Preprint submitted to Elsevier January 17, 2018 a critical level. Our analytical studies, supported by numerical simulations, highlight the sensitivity of antibiotic producing and degrading communities to loss-of-function mutants.

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“…It has been reported that these two mechanisms, influx (via porins) and efflux (via pumps), are controlled by the same complex regulation cascade (5, 10). However, they can be independently expressed (7,8,9,10,13). Regarding K. pneumoniae isolates, the signals corresponding to AcrAB-TolC components in the tested MDR strains did not show significant overstaining while a noticeable reversing effect of PA␤N on these strains was obtained.…”

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Occurrence of Efflux Mechanism and Cephalosporinase Variant in a Population of Enterobacter aerogenes and Klebsiella pneumoniae Isolates Producing Extended-Spectrum β-Lactamases

Tran

Dupont

Lavigne

et al. 2009

Antimicrob Agents Chemother

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We investigated the occurrence of multidrug resistance in 44 Enterobacter aerogenes and Klebsiella pneumoniae clinical isolates. Efflux was involved in resistance in E. aerogenes isolates more frequently than in K. pneumoniae isolates (100 versus 38% of isolates) and was associated with the expression of phenylalanine arginine ␤-naphthylamide-susceptible active efflux. AcrA-TolC overproduction in E. aerogenes isolates was noted. An analysis of four E. aerogenes isolates for which cefepime MICs were high revealed no modification in porin expression but a new specific mutation in the AmpC ␤-lactamase.Enterobacter aerogenes and Klebsiella pneumoniae, two of the most prevalent nosocomial enterobacterial species, can frequently express a multidrug resistance (MDR) phenotype by the acquisition or high-level production of ␤-lactamases in combination with the overproduction of efflux pumps, associated or not with porin alterations in the outer membrane (1,3,7,9,13). Such modifications of envelope permeability, including efflux and influx (porin), in 28 Enterobacter aerogenes and 16 Klebsiella pneumoniae clinical isolates from Nîmes University Hospital, previously studied for extended-spectrum ␤-lactamase (ESBL) profiling and clonal identification, were investigated (11). Moreover, we ascertained the mechanism involved in cefepime resistance in four E. aerogenes isolates showing high-level resistance (MIC ϭ 128 mg/liter).Characterization of the MDR phenotype was carried out by determining the MICs of various structurally unrelated antibiotics selected for their capacities to be expelled and/or to enter cells via porins (Table 1). We used the twofold broth dilution method with Mueller-Hinton broth according to the CLSI guidelines: the tests were carried out with or without the broad-spectrum efflux pump inhibitor (EPI) phenylalanine arginine ␤-naphthylamide (PA␤N). This diamine compound, used at a low concentration (26.3 mg/liter), can increase the activities of chloramphenicol, tetracycline, norfloxacin, and sparfloxacin against various enterobacterial isolates which overproduce efflux pumps such AcrAB-TolC (4, 9, 16). The test results confirmed the existence of a PA␤N-susceptible efflux mechanism in all E. aerogenes and many K. pneumoniae strains, with marked decreases in the MICs of fluoroquinolones and chloramphenicol in the presence of PA␤N (Table 1). Efflux pump activity was identified when the PA␤N addition induced a threefold decrease in the MIC of an antibiotic molecule (4, 9). For the two fluoroquinolones, the PA␤N addition had better efficiency in decreasing the MICs of sparfloxacin than those of norfloxacin. The observed difference in PA␤N efflux inhibition between the two fluoroquinolones may reflect the respective locations of ligands inside the AcrB cavity and the flux competition (20). Yu et al. demonstrated, during previous cocrystalization analyses, the presence of different affinity sites located inside the AcrB pump and suggested that the benefit generated by the conjoint use of an EPI and an antibioti...

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Bacterial resistance to antibiotics: Active efflux and reduced uptake

Cited by 417 publications

References 278 publications

The combination effects of trivalent gold ions and gold nanoparticles with different antibiotics against resistant Pseudomonas aeruginosa

The combination effects of trivalent gold ions and gold nanoparticles with different antibiotics against resistant Pseudomonas aeruginosa

Analysis of stability to cheaters in models of antibiotic degrading microbial communities

Occurrence of Efflux Mechanism and Cephalosporinase Variant in a Population of Enterobacter aerogenes and Klebsiella pneumoniae Isolates Producing Extended-Spectrum β-Lactamases

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