Genomic variations between colistin-susceptible and -resistant Pseudomonas aeruginosa clinical isolates and their effects on colistin resistance

AbstractWhole genome sequencing (WGS) of historical Pseudomonas aeruginosa clinical isolates identified a chromosomal copy of mcr-5 within a Tn3-like transposon in P. aeruginosa MRSN 12280. The isolate was non-susceptible to colistin by broth microdilution and genome analysis revealed no mutations known to confer colistin resistance. To the best of our knowledge this is the first report of mcr in colistin non-susceptible P. aeruginosa.

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EMERGENCE OF PLASMID MEDIATED COLISTIN RESISTANCE GENE MCR-1 IN CARBAPENEM-RESISTANT PSEUDOMONAS AERUGINOSA CLINICAL ISOLATES FROM ALGERIA: A NEW SUCCESSFUL RESISTANCE COMBINATION TOWARD A THERAPEUTIC IMPASSE?

10.21506/j.ponte.2020.4.16 ◽

2020 ◽

Vol 76 (4) ◽

Author(s):

Addouda Abir ◽

Ayachi Ammar ◽

Hassaine Hafida ◽

Dhaouadi Sana ◽

Soufi Leila ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Resistance Gene ◽

Clinical Isolates ◽

Colistin Resistance ◽

Carbapenem Resistant ◽

Therapeutic Impasse

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Chromosomally Encoded mcr-5 in Colistin-Nonsusceptible Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00679-18 ◽

2018 ◽

Vol 62 (8) ◽

Cited By ~ 24

Author(s):

Erik Snesrud ◽

Rosslyn Maybank ◽

Yoon I. Kwak ◽

Anthony R. Jones ◽

Mary K. Hinkle ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Genome Analysis ◽

Clinical Isolates ◽

Whole Genome ◽

Broth Microdilution ◽

Colistin Resistance ◽

Content Type ◽

First Report

ABSTRACT Whole-genome sequencing (WGS) of historical Pseudomonas aeruginosa clinical isolates identified a chromosomal copy of mcr-5 within a Tn3-like transposon in P. aeruginosa MRSN 12280. The isolate was nonsusceptible to colistin by broth microdilution, and genome analysis revealed no mutations known to confer colistin resistance. To the best of our knowledge, this is the first report of mcr in colistin-nonsusceptible P. aeruginosa.

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Cephalosporin nitric oxide-donor prodrug DEA-C3D disperses biofilms formed by clinical cystic fibrosis isolates of Pseudomonas aeruginosa

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz378 ◽

2019 ◽

Vol 75 (1) ◽

pp. 117-125 ◽

Cited By ~ 8

Author(s):

Odel Soren ◽

Ardeshir Rineh ◽

Diogo G Silva ◽

Yuming Cai ◽

Robert P Howlin ◽

...

Keyword(s):

Nitric Oxide ◽

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Laser Scanning ◽

Laser Scanning Microscopy ◽

Clinical Isolates ◽

Nitric Oxide Donor ◽

Confocal Laser ◽

Broth Microdilution Method

Abstract Objectives The cephalosporin nitric oxide (NO)-donor prodrug DEA-C3D (‘DiEthylAmin-Cephalosporin-3′-Diazeniumdiolate’) has been shown to initiate the dispersal of biofilms formed by the Pseudomonas aeruginosa laboratory strain PAO1. In this study, we investigated whether DEA-C3D disperses biofilms formed by clinical cystic fibrosis (CF) isolates of P. aeruginosa and its effect in combination with two antipseudomonal antibiotics, tobramycin and colistin, in vitro. Methods β-Lactamase-triggered release of NO from DEA-C3D was confirmed using a gas-phase chemiluminescence detector. MICs for P. aeruginosa clinical isolates were determined using the broth microdilution method. A crystal violet staining technique and confocal laser scanning microscopy were used to evaluate the effects of DEA-C3D on P. aeruginosa biofilms alone and in combination with tobramycin and colistin. Results DEA-C3D was confirmed to selectively release NO in response to contact with bacterial β-lactamase. Despite lacking direct, cephalosporin/β-lactam-based antibacterial activity, DEA-C3D was able to disperse biofilms formed by three P. aeruginosa clinical isolates. Confocal microscopy revealed that DEA-C3D in combination with tobramycin produces similar reductions in biofilm to DEA-C3D alone, whereas the combination with colistin causes near complete eradication of P. aeruginosa biofilms in vitro. Conclusions DEA-C3D is effective in dispersing biofilms formed by multiple clinical isolates of P. aeruginosa and could hold promise as a new adjunctive therapy to patients with CF.

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Pharmacodynamics of once- versus twice-daily dosing of nebulized amikacin in an in vitro Hollow-Fiber Infection Model against 3 clinical isolates of Pseudomonas aeruginosa

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2021.115329 ◽

2021 ◽

Vol 100 (2) ◽

pp. 115329

Author(s):

Aaron James Heffernan ◽

Fekade Bruck Sime ◽

Saiyuri Naicker ◽

Katherine Andrews ◽

David Ellwood ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Hollow Fiber ◽

Clinical Isolates ◽

Infection Model

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Resistance and Heteroresistance to Colistin in Pseudomonas aeruginosa Isolates from Wenzhou, China

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00556-19 ◽

2019 ◽

Vol 63 (10) ◽

Cited By ~ 8

Author(s):

Jie Lin ◽

Chunquan Xu ◽

Renchi Fang ◽

Jianming Cao ◽

Xiucai Zhang ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Lipid A ◽

Population Analysis ◽

Colistin Resistance ◽

Content Type ◽

Maldi Tof Ms ◽

Expression Levels ◽

Maldi Tof ◽

Broth Microdilution Method ◽

Tof Ms

ABSTRACT The goal was to investigate the mechanisms of colistin resistance and heteroresistance in Pseudomonas aeruginosa clinical isolates. Colistin resistance was determined by the broth microdilution method. Colistin heteroresistance was evaluated by population analysis profiling. Time-kill assays were also conducted. PCR sequencing was performed to detect the resistance genes among (hetero)resistant isolates, and quantitative real-time PCR assays were performed to determine their expression levels. Pulsed-field gel electrophoresis and multilocus sequence typing were performed. Lipid A characteristics were determined via matrix-assisted laser desorption–ionization time of flight mass spectrometry (MALDI-TOF MS). Two resistant isolates and 9 heteroresistant isolates were selected in this study. Substitutions in PmrB were detected in 2 resistant isolates. Among heteroresistant isolates, 8 of 9 heteroresistant isolates had nonsynonymous PmrB substitutions, and 2 isolates, including 1 with a PmrB substitution, had PhoQ alterations. Correspondingly, the expression levels of pmrA or phoP were upregulated in PmrB- or PhoQ-substituted isolates. One isolate also found alterations in ParRS and CprRS. The transcript levels of the pmrH gene were observed to increase across all investigated isolates. MALDI-TOF MS showed additional 4-amino-4-deoxy-l-arabinose (l-Ara4N) moieties in lipid A profiles in (hetero)resistant isolates. In conclusion, both colistin resistance and heteroresistance in P. aeruginosa in this study mainly involved alterations of the PmrAB regulatory system. There were strong associations between mutations in specific genetic loci for lipid A synthesis and regulation of modifications to lipid A. The transition of colistin heteroresistance to resistance should be addressed in future clinical surveillance.

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Risk Factors for and Mechanisms of COlistin Resistance Among Enterobacterales: Getting at the CORE of the Issue

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab145 ◽

2021 ◽

Author(s):

John P Mills ◽

Laura J Rojas ◽

Steve H Marshall ◽

Susan D Rudin ◽

Andrea M Hujer ◽

...

Keyword(s):

Case Control Study ◽

Clinical Isolates ◽

Colistin Resistance ◽

E Coli ◽

The Core ◽

Increased Risk ◽

Recent Emergence ◽

Enterobacter Species ◽

Ann Arbor ◽

Control Study

Abstract Background Despite the recent emergence of plasmid-mediated colistin resistance, the epidemiology and mechanisms of colistin-resistant Enterobacterales (CORE) infections remain poorly understood. Methods A case-case-control study was conducted utilizing routine clinical isolates obtained at a single tertiary health system in Ann Arbor, MI. Patients with CORE isolates from January 1st 2016 to March 31st 2017 were matched 1:1 with patients with colistin-susceptible Enterobacterales (COSE) and uninfected controls. Multivariable logistic regression was used to compare clinical and microbiologic features of patients with CORE and COSE to controls. A subset of available CORE isolates underwent whole genome sequencing to identify putative colistin resistance genes. Results Of 16,373 tested clinical isolates, 166 (0.99%) were colistin-resistant, representing 103 unique patients. Among 103 CORE isolates, 103 COSE isolates, and 102 uninfected controls, antibiotic exposure in the antecedent 90 days and age > 55 years were predictors of both CORE and COSE. Of 33 isolates that underwent WGS, a large variety of mutations associated with colistin resistance were identified, including 4 mcr-1/mcr-1.1 genes and 4 pmrA/B mutations among 9 Escherichia coli isolates; 5 mgrB and 3 PmrA mutations among 8 Klebsiella pneumoniae isolates. Genetic mutations found in Enterobacter species were not associated with known phenotypic colistin resistance. Conclusions Increased age and prior antibiotic receipt were associated with increased risk for patients with CORE, and for patients with COSE. Mcr-1, pmrA/B, and mgrB were the predominant colistin resistance-associated mutations identified among E. coli and K. pneumoniae, respectively. Mechanisms of colistin resistance among Enterobacter species could not be determined.

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