Role of RND Efflux Pumps in Drug Resistance of Cystic Fibrosis Pathogens

Scoffone, Viola Camilla; Trespidi, Gabriele; Barbieri, Giulia; Irudal, Samuele; Perrin, Elena; Buroni, Silvia

doi:10.3390/antibiotics10070863

Cited by 29 publications

(28 citation statements)

References 188 publications

(307 reference statements)

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“…As MIC values were above 0Á032 mg ml À1 , isolates were considered to have a high level of resistance to Cip. The differences in their MICs may be related to mutations in regulatory genes that enhance the expression of Mex pumps (mexR and mexZ) and in antibiotic target genes (gyrA and parC) (Serra et al 2019;Scoffone et al 2021). The molecular characterization of these isolates was not carried out in this study.…”

Section: Resultsmentioning

confidence: 98%

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In vitro activity of honey, total alkaloids of Sophora alopecuroides and matrine alone and in combination with antibiotics against multidrug-resistant Pseudomonas aeruginosa isolates

Jaktaji

Koochaki

2022

Letters in Applied Microbiology

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Natural products, including honey, total alkaloids of Sophora alopecuroides (TASA) and matrine have been used in combination with antibiotics against various pathogenic bacteria. However, there are limited data on the antibacterial activity of these natural products in combination against multidrug‐resistant Pseudomonas aeruginosa strains. The in vitro activity of honey, TASA and matrine alone and in combination with antibiotics against P. aeruginosa isolates was investigated. In this study, four biofilm‐producing P. aeruginosa isolates, which were resistant to multiple antibiotics, were used. These natural products were not the most effective single agent against four isolates. The fractional inhibitory concentration index method revealed the synergistic effect of matrine and TASA‐honey in combination with ciprofloxacin (Cip) against all tested isolates. When these combinations were used, the resistance of isolates to Cip was decreased significantly (six to eightfold reduction in the minimum inhibitory concentration of Cip. The disk diffusion method showed that all isolates were resistant to β‐lactams. Combinations of these antibiotics with TASA and matrine changed slightly the activity of either antibiotic used as a single agent. All isolates produced metallo‐β‐lactamase enzymes (MBL). Pretreatment isolates with Cip‐matrine and Cip‐TASA‐honey resulted in a statistically downregulated expression of the mexA gene. These natural products can be used against overactivating MexAB‐OprM but not MBL‐producing P. aeruginosa isolates.

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Section: Resultsmentioning

confidence: 98%

“…2019; Scoffone et al . 2021). The molecular characterization of these isolates was not carried out in this study.…”

Section: Resultsmentioning

confidence: 99%

In vitro activity of honey, total alkaloids of Sophora alopecuroides and matrine alone and in combination with antibiotics against multidrug-resistant Pseudomonas aeruginosa isolates

Jaktaji

Koochaki

2022

Letters in Applied Microbiology

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“…The Multi Drug Resistance (MDR) phenotype of P. aeruginosa is a key source of concern. In addition to traditional drug resistance mechanisms, P. aeruginosa can develop resistance to antibiotics as the infection progresses (Scoffone et al, 2021). Efflux pumps in the Resistance-Nodulation-cell Division (RND) family are able to translocate various compounds (including antibiotics) out of the bacterial cell in an atypical manner,…”

Section: Resultsmentioning

confidence: 99%

“…In P. aeruginosa, there are 11 RND effluxes. Using efflux pump inhibitors to improve the clinical effectiveness of various antibiotics is a unique and promising strategy for treating multidrug-resistant bacteria (Scoffone et al, 2021;Zechini and Versace, 2009). Higher levels of resistance may be attributed to efflux pump overexpression, which can become unstable when specific phenotypic resistance inducers or constitutive inducers for acquired resistance are revealed (Langendonk et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Molecular detection of mexXY-oprM, mexPQ-opmE Efflux pumps in multi-drug resistant Pseudomonas aeruginosa isolates in patients referred to teaching hospitals in Babylon province, Iraq

Zwaid¹,

Al-Dahmoshi

2022

JANS

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One of the global health issues is antibiotic resistance in Pseudomonas aeruginosa, a causative agent of bacterial infections due to multidrug resistance (MDR), which may be mediated by efflux pumps' overexpression.The present study investigated the prevalence of mexXY-oprM, mexPQ-opmE genes as encoding agents of efflux pumps and the determination of antibiotic resistance rate in clinical isolates of P. aeruginosa.Different clinical specimens of infectious patients, such as wounds, urine, blood, discharge, and abscesses except for stool, were examined. Identification of the isolates was performed using Pseudomonas chromogenic agar. A selective medium for the isolation of P. aeruginosa, used to screen 79 isolates. The results were validated by Polymerase chain reaction (PCR) utilizing particular primer pairs for the 16S rDNA gene of Pseudomonas spp. for identification of the isolates after incubation at 37°C for 24 hours. According to Clinical and Laboratory Standards Institute (CLSI) (2021) recommendations, a microbial susceptibility test was performed using the Kirby–Bauer disk diffusion method. P. aeruginosa was extremely resistant to ceftazidime (93.6%) and cefepime (77.2 %). In contrast, imipenem (77.2%) and meropenem (67%) showed high sensitivity. Finally, mexXY-oprM, mexPQ-opmE genes were investigated by PCR technique. Molecular investigation revealed mexX 43%, mexY 51.89%, oprM 48.1%, mexP 36.70% mexQ 46.83% and opmE 51.89%. The present study concluded that mexXY-oprM and mexPQ-opmE may have a role in P. aeruginosa resistance to various antibiotics. Identifying resistant isolates and antibiotic monitoring programs is essential to prevent the spread of MDR isolates.

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“…A key contributor to aminoglycoside resistance is the MexXY-OprM efflux pump that exports aminoglycosides out of the bacterial cells [7][8][9][10]. MexXY-OprM also has a role in resistance to fluoroquinolones, macrolides, tetracycline, chloramphenicol, some β-lactams and polymixins [7,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Aminoglycoside resistance in Pseudomonas aeruginosa: the contribution of the MexXY-OprM efflux pump varies between isolates

Thacharodi

Lamont

2022

Journal of Medical Microbiology

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Introduction. Aminoglycoside antibiotics are widely used to treat infections of Pseudomonas aeruginosa . The MexXY-OprM efflux pump is an important contributor to aminoglycoside tolerance in P. aeruginosa reference strains and expression of the mexXY genes is repressed by the MexZ repressor protein. Direct investigation of the role of this efflux pump in clinical isolates is relatively limited. Hypothesis. The contribution of MexXY-OprM to P. aeruginosa aminoglycoside resistance is isolate-specific. Aim. To quantify the role of MexXY-OprM and its repressor, MexZ, in clinical isolates of P. aeruginosa. Methodology. The mexXY genes were deleted from ten clinical isolates of P. aeruginosa , and the mexZ gene from nine isolates. Antimicrobial susceptibility testing was carried out for commonly used antipseudomonal drugs on the engineered mutants and the isogenic wild-type isolates. RT-qPCR was used to measure expression of the mexX gene. Results. All but one of the mexXY mutants were more susceptible to the clinically used aminoglycosides tobramycin, gentamicin and amikacin but the degree to which susceptibility increased varied greatly between isolates. The mexXY mutants were also more susceptible to a fluoroquinolone, ciprofloxacin. In three isolates with functional MexZ, deletion of mexZ increased expression of mexXY and aminoglycoside tolerance. Conversely, deleting mexZ from six clinical isolates with mexZ sequence variants had little or no effect on expression of mexXY or on aminoglycoside susceptibility, consistent with the variants abolishing MexZ function. Genome analysis showed that over 50 % of 619 clinical isolates had sequence variants predicted to reduce the affinity of MexZ for DNA, likely increasing mexXY expression and hence efflux of aminoglycosides. Conclusion. Our findings show that the interplay between MexXY, MexZ and the level of mexXY expression plays an important role in aminoglycoside resistance in clinical isolates of P. aeruginosa but the magnitude of the contribution of this efflux pump to resistance is isolate-specific.

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Role of RND Efflux Pumps in Drug Resistance of Cystic Fibrosis Pathogens

Cited by 29 publications

References 188 publications

In vitro activity of honey, total alkaloids of Sophora alopecuroides and matrine alone and in combination with antibiotics against multidrug-resistant Pseudomonas aeruginosa isolates

In vitro activity of honey, total alkaloids of Sophora alopecuroides and matrine alone and in combination with antibiotics against multidrug-resistant Pseudomonas aeruginosa isolates

Molecular detection of mexXY-oprM, mexPQ-opmE Efflux pumps in multi-drug resistant Pseudomonas aeruginosa isolates in patients referred to teaching hospitals in Babylon province, Iraq

Aminoglycoside resistance in Pseudomonas aeruginosa: the contribution of the MexXY-OprM efflux pump varies between isolates

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