scholarly journals Chromosomally Encoded mcr-5 in Colistin Non-susceptible Pseudomonas aeruginosa

2018 ◽  
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 ◽  
First Report ◽  
Chromosomal Copy

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.

scholarly journals Chromosomally Encoded mcr-5 in Colistin-Nonsusceptible Pseudomonas aeruginosa

2018 ◽  
Vol 62 (8) ◽  
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.

scholarly journals Cefiderocol Activity against Clinical Pseudomonas aeruginosa Isolates Exhibiting Ceftolozane-Tazobactam Resistance

2021 ◽  
Author(s):  
Patricia J Simner ◽  
Stephan Beisken ◽  
Yehudit Bergman ◽  
Andreas E Posch ◽  
Sara E Cosgrove ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Binding Sites ◽  
Whole Genome ◽  
The Novel ◽  
Broth Microdilution ◽  
Mechanisms Of Resistance ◽  
Fold Reduction ◽  
Target Binding

Abstract Objective Mutations in the AmpC-AmpR region are associated with treatment-emergent ceftolozane-tazobactam (TOL-TAZ) and ceftazidime-avibactam (CAZ-AVI) resistance. We sought to determine if these mutations impact susceptibility to the novel cephalosporin-siderophore compound cefiderocol. Methods Thirty-two paired isolates from 16 patients with index P. aeruginosa isolates susceptible to TOL-TAZ and subsequent P. aeruginosa isolates available after TOL-TAZ exposure from January 2019 to December 2020 were included. TOL-TAZ, CAZ-AVI, imipenem-relebactam (IMI-REL), and cefiderocol minimum inhibitory concentrations (MICs) were determined using broth microdilution. Whole genome sequencing of paired isolates was used to identify mechanisms of resistance to cefiderocol that emerged, focusing on putative mechanisms of resistance to cefiderocol or earlier siderophore-antibiotic conjugates based on the previously published literature. Results Analyzing the 16 pairs of P. aeruginosa isolates, ≥4-fold increases in cefiderocol MICs occurred in 4 of 16 isolates. Cefiderocol non-susceptibility criteria was met for only 1 of the 4 isolates, using Clinical and Laboratory Standards Institute criteria. Specific mechanisms identified included the following: AmpC E247K (2 isolates), MexR A66V and L57D (1 isolate each), and AmpD G116D (1 isolate) substitutions. For both isolates with AmpC E247K mutations, ≥4-fold MIC increases occurred for both TOL-TAZ and CAZ-AVI, while a ≥4-fold reduction in IMI-REL MICs was observed. Conclusions Our findings suggest that alterations in the target binding sites of P. aeruginosa derived AmpC β-lactamases have the potential to reduce the activity of three of four novel β-lactams (i.e., ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol) and potentially increase susceptibility to imipenem-relebactam. These findings are in need of validation in a larger cohort.

scholarly journals 697. Pseudomonas aeruginosa PcrV and Psl, the Molecular Targets of Bispecific Monoclonal Antibody MEDI3902, Are Conserved Among Diverse Hospital Isolates Collected From an International Surveillance Study

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S251-S251
Author(s):  
David E Tabor
Keyword(s):  
Crystal Structure ◽  
Monoclonal Antibody ◽  
Pseudomonas Aeruginosa ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Crystal Structure Analysis ◽  
Clinical Isolates ◽  
Whole Genome ◽  
Mechanically Ventilated ◽  
Bispecific Monoclonal Antibody

Abstract Background Pseudomonas aeruginosa is a frequent cause of life-threatening infections in mechanically ventilated patients and is associated with high mortality rates. Bispecific monoclonal antibody MEDI3902 targeting Pa type-3-secretion system (PcrV) and the Psl exopolysaccharide is currently under phase 2b development for the prevention of pneumonia in mechanically ventilated subjects with Pa colonization in the lower respiratory tract. In this study, we sought to survey a vast collection of global Pa clinical isolates for presence of pcrV and psl loci and MEDI3902 epitope conservation to evaluate the magnitude of Pa strain coverage by MEDI3902. Methods 913 Pa clinical isolates were collected from diverse patients and geographical locations in 2004–2014. Whole genome sequencing of the full collection was performed via MiSeq 2 × 250 runs (Illumina®). PcrV and Psl expression was detected by immunoblotting and ELISA, respectively. The crystal structure of anti-PcrV fab and PcrV fragment complex-crystals was solved at 2.8 Å resolution. MEDI3902 activity against representative isolates was tested in cytotoxicity and opsonophagocytosis assays and in a murine pneumonia model. Results Whole-genome sequencing revealed intact pcrV and psl genetic elements in 99% and 94% of isolates, respectively. We identified 46 variants of PcrV that were all bound by the anti-PcrV moiety of MEDI3902 and confirmed through crystal structure analysis that antibody-antigen contact residues were preserved in all variants. Similarly, anti-Psl binding was confirmed for selected isolates containing the complete Psl operon and strains lacking non-essential psl genes. Importantly, 99.9% of isolates contained the full complement of either genetic element. Consistent with these results, we observed potent MEDI3902 activity against diverse strain types, including strains that expressed only a single target. Conclusion Our results indicate PcrV and Psl are highly prevalent in recent clinical isolates from around the world, suggesting that MEDI3902 can mediate broad coverage against Pa. Disclosures D. E. Tabor, Astra Zeneca: employee, Salary.

scholarly journals Mycobacterium chimaera genomics with regard to epidemiological and clinical investigations conducted for the open-chest post-surgical Mycobacterium chimaera infections outbreak

2021 ◽  
Author(s):  
Emmanuel Lecorche ◽  
Côme Daniau ◽  
Kevin La ◽  
Faiza Mougari ◽  
Hanaa Benmansour ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Clinical Isolates ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Healthcare Facilities ◽  
Open Chest

Abstract Background Post-surgical infections due to Mycobacterium chimaera appeared as a novel nosocomial threat in 2015, with a worldwide outbreak due to contaminated heater-cooler units used in open chest surgery. We report the results of investigations conducted in France including whole genome sequencing comparison of patient and HCU isolates. Methods We sought M. chimaera infection cases from 2010 onwards through national epidemiological investigations in healthcare facilities performing cardiopulmonary bypass together with a survey on good practices and systematic heater-cooler unit microbial analyses. Clinical and HCU isolates were subjected to whole genome sequencing analyzed with regards to the reference outbreak strain Zuerich-1. Results Only two clinical cases were shown to be related to the outbreak, although 23% (41/175) heater-cooler units were declared positive for M. avium complex. Specific measures to prevent infection were applied in 89% (50/56) healthcare facilities although only 14% (8/56) of them followed the manufacturer maintenance recommendations. Whole genome sequencing comparison showed that the clinical isolates and 72% (26/36) of heater-cooler unit isolates belonged to the epidemic cluster. Within clinical isolates, 5 to 9 non-synonymous single nucleotide polymorphisms were observed, among which an in vivo mutation in a putative efflux pump gene observed in a clinical isolate obtained for one patient under antimicrobial treatment. Conclusions Cases of post-surgical M. chimaera infections were declared to be rare in France, although heater-cooler units were contaminated as in other countries. Genomic analyses confirmed the connection to the outbreak and identified specific single nucleotide polymorphisms, including one suggesting fitness evolution in vivo.

scholarly journals Tracing Melioidosis Back to the Source: Using Whole-Genome Sequencing To Investigate an Outbreak Originating from a Contaminated Domestic Water Supply

2015 ◽  
Vol 53 (4) ◽  
pp. 1144-1148 ◽  
Author(s):  
Evan McRobb ◽  
Derek S. Sarovich ◽  
Erin P. Price ◽  
Mirjam Kaestli ◽  
Mark Mayo ◽  
...  
Keyword(s):  
Water Supply ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Clinical Isolates ◽  
Whole Genome ◽  
Northern Australia ◽  
Source Attribution ◽  
Environmental Strain ◽  
Content Type ◽  
Groundwater Supply

Melioidosis, a disease of public health importance in Southeast Asia and northern Australia, is caused by the Gram-negative soil bacillusBurkholderia pseudomallei. Melioidosis is typically acquired through environmental exposure, and case clusters are rare, even in regions where the disease is endemic.B. pseudomalleiis classed as a tier 1 select agent by the Centers for Disease Control and Prevention; from a biodefense perspective, source attribution is vital in an outbreak scenario to rule out a deliberate release. Two cases of melioidosis within a 3-month period at a residence in rural northern Australia prompted an investigation to determine the source of exposure.B. pseudomalleiisolates from the property's groundwater supply matched the multilocus sequence type of the clinical isolates. Whole-genome sequencing confirmed the water supply as the probable source of infection in both cases, with the clinical isolates differing from the likely infecting environmental strain by just one single nucleotide polymorphism (SNP) each. For the first time, we report a phylogenetic analysis of genomewide insertion/deletion (indel) data, an approach conventionally viewed as problematic due to high mutation rates and homoplasy. Our whole-genome indel analysis was concordant with the SNP phylogeny, and these two combined data sets provided greater resolution and a better fit with our epidemiological chronology of events. Collectively, this investigation represents a highly accurate account of source attribution in a melioidosis outbreak and gives further insight into a frequently overlooked reservoir ofB. pseudomallei. Our methods and findings have important implications for outbreak source tracing of this bacterium and other highly recombinogenic pathogens.

scholarly journals Whole-Genome Sequencing Confirms that Burkholderia pseudomallei Multilocus Sequence Types Common to Both Cambodia and Australia Are Due to Homoplasy

2014 ◽  
Vol 53 (1) ◽  
pp. 323-326 ◽  
Author(s):  
Birgit De Smet ◽  
Derek S. Sarovich ◽  
Erin P. Price ◽  
Mark Mayo ◽  
Vanessa Theobald ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genome Analysis ◽  
Burkholderia Pseudomallei ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Content Type ◽  
Sequence Types

Burkholderia pseudomalleiisolates with shared multilocus sequence types (STs) have not been isolated from different continents. We identified two STs shared between Australia and Cambodia. Whole-genome analysis revealed substantial diversity within STs, correctly identified the Asian or Australian origin, and confirmed that these shared STs were due to homoplasy.

scholarly journals Integrating Culture-based Antibiotic Resistance Profiles with Whole-genome Sequencing Data for 11,087 Clinical Isolates

2019 ◽  
Vol 17 (2) ◽  
pp. 169-182 ◽  
Author(s):  
Valentina Galata ◽  
Cédric C. Laczny ◽  
Christina Backes ◽  
Georg Hemmrich-Stanisak ◽  
Susanne Schmolke ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Clinical Isolates ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data
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