Mechanisms for Development of Ciprofloxacin Resistance in a Clinical Isolate of Pseudomonas aeruginosa

Xu, Congjuan; Liu, Huimin; Pan, Xiaolei; Ma, Zhenzhen; Wang, Dan; Zhang, Xinxin; Zhu, Guangbo; Bai, Fang; Cheng, Zhihui; Wu, Weihui; Jin, Yongxin

doi:10.3389/fmicb.2020.598291

Cited by 17 publications

(79 citation statements)

References 46 publications

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“…Total RNA isolation and RT-qPCR were carried out as described in our early studies ( Xu et al, 2020a ; Xu et al, 2020b ). Overnight bacterial strains were subcultured to the log phase (OD 600 = 1.0) at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…RNAseq was performed as described before ( Xu et al, 2020a , b ). The quality and quantity of total RNAs from CSP18 and ARP36 were determined with a Bioanalyzer 2100 system (Agilent Technologies, Palo Alto, CA, United States), a NanoDrop spectrophotometer, and electrophoresis on a 1% (wt/vol) agarose gel.…”

Section: Methodsmentioning

confidence: 99%

“…DNA purification and resequencing were conducted as previously described ( Xu et al, 2020a , b ). Genomic DNA of bacterial strains was extracted with DNA isolation kit (Tiangen Biotec, Beijing, China).…”

Section: Methodsmentioning

confidence: 99%

“…The early strain was isolated soon after the patient was admitted to the hospital, while the later one was isolated after the antibiotic therapy for 7 days. The early isolate CSP18 [named as CSP18 due to its sensitivity to ciprofloxacin in our earlier study ( Xu et al, 2020a )]was susceptible to aztreonam, while the later one ARP36 was aztreonam resistant. Therefore, we wanted to explore the molecular mechanisms of aztreonam resistance in the resistant clinical isolate in comparison with the sensitive one in the clinical setting.…”

Section: Introductionmentioning

confidence: 99%

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A MexR Mutation Which Confers Aztreonam Resistance to Pseudomonas aeruginosa

Zhang

et al. 2021

Front. Microbiol.

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Therapy for Pseudomonas aeruginosa infections is hard due to its high natural and acquirable antibiotic resistance. After colonization in the hosts, P. aeruginosa commonly accumulates genomic mutations which confer them antibiotic resistance and better adaptations to the host environment. Deciphering the mechanisms of antibiotic resistance development in the clinical setting may provide critical insights into the design of effective combinatory antibiotic therapies to treat P. aeruginosa infections. In this work, we demonstrate a resistance mechanism to aztreonam of a clinical isolate (ARP36) in comparison with a sensitive one (CSP18). RNAseq and genomic DNA resequencing were carried out to compare the global transcriptional profiles and in the clinical setting genomic profiles between these two isolates. The results demonstrated that hyperexpression of an efflux pump MexAB-OprM caused by a R70Q substitution in MexR, contributed to the increased resistance to aztreonam in the isolate ARP36. Simulation of mexR of ARP36 by gene editing in CSP18 conferred CSP18 an ARP36-like susceptibility to the aztreonam. The R70Q substitution prevented MexR from binding to the intergenic region between mexR and mexAB-oprM operon, with no impact on its dimerization. The presented experimental results explain for the first time why the clinically relevant R70Q substitution in the MexR derepresses the expression of mexAB-oprM in P. aeruginosa.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A MexR Mutation Which Confers Aztreonam Resistance to Pseudomonas aeruginosa

Zhang

et al. 2021

Front. Microbiol.

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“…It has been documented that CIP resistance can arise through the acquisition of mutations in genes encoding the target proteins of CIP and regulators of efflux pumps (Rehman et al, 2019 ; Xu et al, 2021 ). Furthermore, recent advances show a global response of P. aeruginosa to CIP stress.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Biosynthesis of Fatty Acids Contributes to Ciprofloxacin Resistance in Pseudomonas aeruginosa

Tang

Zhu

et al. 2022

Front. Microbiol.

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Antibiotic-resistant Pseudomonas aeruginosa is insensitive to antibiotics and difficult to deal with. An understanding of the resistance mechanisms is required for the control of the pathogen. In this study, gas chromatography–mass spectrometer (GC-MS)-based metabolomics was performed to identify differential metabolomes in ciprofloxacin (CIP)-resistant P. aeruginosa strains that originated from P. aeruginosa ATCC 27853 and had minimum inhibitory concentrations (MICs) that were 16-, 64-, and 128-fold (PA-R16CIP, PA-R64CIP, and PA-R128CIP, respectively) higher than the original value, compared to CIP-sensitive P. aeruginosa (PA-S). Upregulation of fatty acid biosynthesis forms a characteristic feature of the CIP-resistant metabolomes and fatty acid metabolome, which was supported by elevated gene expression and enzymatic activity in the metabolic pathway. The fatty acid synthase inhibitor triclosan potentiates CIP to kill PA-R128CIP and clinically multidrug-resistant P. aeruginosa strains. The potentiated killing was companied with reduced gene expression and enzymatic activity and the returned abundance of fatty acids in the metabolic pathway. Consistently, membrane permeability was reduced in the PA-R and clinically multidrug-resistant P. aeruginosa strains, which were reverted by triclosan. Triclosan also stimulated the uptake of CIP. These findings highlight the importance of the elevated biosynthesis of fatty acids in the CIP resistance of P. aeruginosa and provide a target pathway for combating CIP-resistant P. aeruginosa.

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Antimicrobial Photodynamic Therapy for the Remote Eradication of Bacteria

Xin

Kwek

et al. 2023

ChemPlusChem

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The emergence of multi‐drug resistant bacteria strains has been an uphill battle in modern healthcare worldwide, due to the increasing difficulty of killing them. The evolving pathogenicity of bacteria has led to researchers searching for more effective antimicrobial therapeutics to successfully eliminate them without undesirable consequences to the human body. In recent years, antimicrobial photodynamic therapy (APDT), an obsolete technique for cancer treatments, has been reported to eradicate bacteria and biofilm‐related infections. The principle of antimicrobial photodynamic therapy solely relies on the photosensitizers (PSs) generating reactive oxygen species, in the presence of oxygen and light, to destroy pathogens. Thus, it can target a broad spectrum of microorganisms, owing to the indirect interaction between PSs and the bacteria, resulting in the less likelihood for the development of drug resistant bacteria strains. This review will focus on the recent progress of APDT in the last five years and some future perspectives of APDT. The mechanism of APDT against bacteria and biofilms, various PSs used for APDT, and some common multidrug‐resistant bacteria strains will be briefly introduced. The reported in vivo applications of APDT in the several types of bacterial infections that includes periodontitis, wound infections, keratitis, endophthalmitis and tuberculosis in the last five years will be summarized in detail.

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Mechanisms for Development of Ciprofloxacin Resistance in a Clinical Isolate of Pseudomonas aeruginosa

Cited by 17 publications

References 46 publications

A MexR Mutation Which Confers Aztreonam Resistance to Pseudomonas aeruginosa

A MexR Mutation Which Confers Aztreonam Resistance to Pseudomonas aeruginosa

Enhanced Biosynthesis of Fatty Acids Contributes to Ciprofloxacin Resistance in Pseudomonas aeruginosa

Antimicrobial Photodynamic Therapy for the Remote Eradication of Bacteria

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