Efflux Pumps as an Important Mechanism for Quinolone Resistance

Vilà, Jordi; Fàbrega, Anna; Roca, Ignasi; Hernandez, Alvaro G.; Martínez, José Luis

doi:10.1002/9780470920541.ch5

Cited by 18 publications

(7 citation statements)

References 271 publications

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“…Mutants of E. coli with decreased OmpF expression have a 2-to 4-fold decrease in susceptibility to quinolones. Several efflux pumps which affect quinolones have been described in E. coli (Vila et al 2011) (Table 2). However, the most important efflux pump is that encoded in the acrAB operon, in which the acrB gene encodes an inner membrane protein (AcrB), which is an efflux transporter across the inner membrane, and the acrA gene, which encodes a membrane fusion protein (AcrA).…”

Section: Fluoroquinolone Resistancementioning

confidence: 99%

Escherichia coli: an old friend with new tidings

Vila

Sáez-López

Johnson

et al. 2016

FEMS Microbiology Reviews

286

217

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Escherichia coli is one of the most-studied microorganisms worldwide but its characteristics are continually changing. Extraintestinal E. coli infections, such as urinary tract infections and neonatal sepsis, represent a huge public health problem. They are caused mainly by specialized extraintestinal pathogenic E. coli (ExPEC) strains that can innocuously colonize human hosts but can also cause disease upon entering a normally sterile body site. The virulence capability of such strains is determined by a combination of distinctive accessory traits, called virulence factors, in conjunction with their distinctive phylogenetic background. It is conceivable that by developing interventions against the most successful ExPEC lineages or their key virulence/colonization factors the associated burden of disease and health care costs could foreseeably be reduced in the future. On the other hand, one important problem worldwide is the increase of antimicrobial resistance shown by bacteria. As underscored in the last WHO global report, within a wide range of infectious agents including E. coli, antimicrobial resistance has reached an extremely worrisome situation that ‘threatens the achievements of modern medicine’. In the present review, an update of the knowledge about the pathogenicity, antimicrobial resistance and clinical aspects of this ‘old friend’ was presented.

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Section: Fluoroquinolone Resistancementioning

confidence: 99%

Escherichia coli: an old friend with new tidings

Vila

Sáez-López

Johnson

et al. 2016

FEMS Microbiology Reviews

286

217

View full text Add to dashboard Cite

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“…However, it is significantly complicated and difficult to control infections when drug resistances are occurring (Murray ; Vila et al . ; Tateda ). In addition to the patient's own microbial communities, invasive Candida albicans are more likely to be those pathogenic micro‐organisms on the surfaces of various objects, such as floors and worktables in the environment surrounding infected patients (Vazquez et al .…”

Section: Introductionmentioning

confidence: 98%

The cellular and molecular mechanism of glutaraldehyde-didecyldimethylammonium bromide as a disinfectant againstCandida albicans

et al. 2018

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Objectives: In our previous research, we have developed a new combination disinfectant, glutaraldehyde-didecyldimethylammonium bromide (GD). It was verified that GD had a strong effect on both Escherichia coli and Staphylococcus aureus. In this work, Candida albicans was selected as an object, and it could be killed by GD. We aimed to investigate the cellular and molecular mechanism of GD effecting on C. albicans. Methods and Results: The results of sterilization experiment indicated that GD was effective on C. albicans. Flow cytometry and atomic absorption spectrometry were applied to detect cell membrane damage of C. albicans. Luciferase reaction and Bradford method were carried out to detect ATP content and protein quantitation. Transmission electron microscopy was used for intracellular organelles morphological observation. In order to study changes in mitochondrial membrane potential, Rh 123 was used as an indicator. DNA conformation analysis was performed by molecular modelling and circular dichroism. The results indicated that membrane permeability was increased rapidly owing to GD effect, and the leaked K + and Mg 2+ were about 12Á1 and 12Á4 times those of the control, respectively, at 10 min after GD treatment. Simultaneously, ATP and protein also leaked rapidly out of the cell. Mitochondrial membrane potential was destroyed, succinic dehydrogenase activity was significantly decreased and DNA conformation was changed because of GD action. Conclusions: Glutaraldehyde-didecyldimethylammonium bromide disinfected C. albicans through distorting cell membrane integrity and permeability, disturbing the intracellular homeostasis by intracellular substances leakage, especially K + , Mg 2+ , ATP and protein, causing electrolyte imbalance of mitochondria, changing DNA structure, which finally led to cell death.

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“…Particularly relevant is the activity of chromosomally-encoded multidrug resistance (MDR) efflux pumps ( Vila and Martínez, 2008 ; Hernando-Amado et al, 2016 ). Further, the acquisition of mutation-driven resistance is common in this opportunistic pathogen, particularly along chronic infections ( Oliver et al, 2015 ; Palmer and Whiteley, 2015 ; Lopez-Causape et al, 2018 ), where the constitutive overexpression of MDR efflux pumps is one of the biggest problems to eradicate these infections ( Vila and Martínez, 2008 ; Vila et al, 2011 ; Hernando-Amado et al, 2016 ). Efflux pumps exhibit different functions, with physiological and ecological significances that go beyond their activity as antibiotic resistance elements ( Piddock, 2006 ; Martinez et al, 2009 ; Alcalde-Rico et al, 2016 ; Hernando-Amado et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Role of the Multidrug Resistance Efflux Pump MexCD-OprJ in the Pseudomonas aeruginosa Quorum Sensing Response

et al. 2018

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Multidrug efflux pumps constitute a category of antibiotic resistance determinants that are a part of the core bacterial genomes. Given their conservation, it is conceivable that they present functions beyond the extrusion of antibiotics currently used for therapy. Pseudomonas aeruginosa stands as a relevant respiratory pathogen, with a high prevalence at hospitals and in cystic fibrosis patients. Part of its success relies on its low susceptibility to antibiotics and on the production of virulence factors, whose expression is regulated in several cases by quorum sensing (QS). We found that overexpression of the MexCD-OprJ multidrug efflux pump shuts down the P. aeruginosa QS response. Our results support that MexCD-OprJ extrudes kynurenine, a precursor of the alkyl-quinolone signal (AQS) molecules. Anthranilate and octanoate, also AQS precursors, do not seem to be extruded by MexCD-OprJ. Kynurenine extrusion is not sufficient to reduce the QS response in a mutant overexpressing this efflux pump. Impaired QS response is mainly due to the extrusion of 4-hydroxy-2-heptylquinoline (HHQ), the precursor of the Pseudomonas Quinolone Signal (PQS), leading to low PQS intracellular levels and reduced production of QS signal molecules. As the consequence, the expression of QS-regulated genes is impaired and the production of QS-regulated virulence factors strongly decreases in a MexCD-OprN P. aeruginosa overexpressing mutant. Previous work showed that MexEF-OprJ, another P. aeruginosa efflux pump, is also able of extruding kynurenine and HHQ. However, opposite to our findings, the QS defect in a MexEF-OprN overproducer is due to kynurenine extrusion. These results indicate that, although efflux pumps can share some substrates, the affinity for each of them can be different. Although the QS response is triggered by population density, information on additional elements able of modulating such response is still scarce. This is particularly important in the case of P. aeruginosa lung chronic infections, a situation in which QS-defective mutants are accumulated. If MexCD-OprJ overexpression alleviates the cost associated to triggering the QS response when un-needed, it could be possible that MexCD-OprJ antibiotic resistant overproducer strains might be selected even in the absence of antibiotic selective pressure, acting as antibiotic resistant cheaters in heterogeneous P. aeruginosa populations.

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Efflux Pumps as an Important Mechanism for Quinolone Resistance

Cited by 18 publications

References 271 publications

Escherichia coli: an old friend with new tidings

Escherichia coli: an old friend with new tidings

The cellular and molecular mechanism of glutaraldehyde-didecyldimethylammonium bromide as a disinfectant againstCandida albicans

Role of the Multidrug Resistance Efflux Pump MexCD-OprJ in the Pseudomonas aeruginosa Quorum Sensing Response

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