scholarly journals Transmission and antibiotic resistance of Achromobacter in cystic fibrosis

2021 ◽  
Author(s):  
Migle Gabrielaite ◽  
Jennifer A. Bartell ◽  
Niels Nørskov-Lauritsen ◽  
Tacjana Pressler ◽  
Finn C. Nielsen ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Antibiotic Resistance ◽  
Severe Disease ◽  
Treatment Strategies ◽  
Clinic Visit ◽  
Resistance Development ◽  
Epidemiological Analysis ◽  
Maldi Tof ◽  
First Time ◽  
Resistance Data

Achromobacter species are increasingly being detected in patients with cystic fibrosis (CF), and this emerging pathogen is associated with antibiotic resistance and more severe disease outcomes. Nonetheless, little is known about the extent of transmission and antibiotic resistance development in Achromobacter infections. We sequenced the genomes of 101 clinical isolates of Achromobacter (A. xylosoxidans based on MALDI-TOF/API N20 typing) collected from 51 patients with CF—the largest longitudinal dataset to-date. We performed phylogenetic analysis on the genomes and combined this with epidemiological and antibiotic resistance data to identify patient-to-patient transmission and development of antibiotic resistance. We confirmed that MALDI-TOF/API N20 was not sufficient for Achromobacter species-level typing, and that the population of Achromobacter isolates was composed of five different species where A. xylosoxidans accounted for 52% of infections. Most patients were infected by unique Achromobacter clone types; nonetheless, suspected patient-to-patient transmission cases identified by shared clone types were observed in 35% (N=18) of patients. In 15 of 16 cases the suspected transmissions were further supported by genome- or clinic visit-based epidemiological analysis. Finally, we found that resistance developed over time. We show that whole-genome sequencing (WGS) is essential for Achromobacter species typing and patient-to-patient transmission identification which was identified in A. ruhlandii, A. xylosoxidans and, for the first time, A. insuavis. Furthermore, we show that the development of antibiotic resistance is associated with chronic Achromobacter infections. Our findings emphasize that transmission and antibiotic resistance should be considered in future treatment strategies.

scholarly journals Transmission and antibiotic resistance of Achromobacter in cystic fibrosis

2020 ◽  
Author(s):  
Migle Gabrielaite ◽  
Jennifer A. Bartell ◽  
Niels Nørskov-Lauritsen ◽  
Tacjana Pressler ◽  
Finn C. Nielsen ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Antibiotic Resistance ◽  
Severe Disease ◽  
Treatment Strategies ◽  
Clinic Visit ◽  
Resistance Development ◽  
Epidemiological Analysis ◽  
Maldi Tof ◽  
First Time ◽  
Resistance Data

AbstractAchromobacter species are increasingly being detected in patients with cystic fibrosis (CF), and this emerging pathogen is associated with antibiotic resistance and more severe disease outcomes. Nonetheless, little is known about the extent of transmission and antibiotic resistance development in Achromobacter infections.We sequenced the genomes of 101 clinical isolates of Achromobacter (A. xylosoxidans based on MALDI-TOF/API N20 typing) collected from 51 patients with CF—the largest longitudinal dataset to-date. We performed phylogenetic analysis on the genomes and combined this with epidemiological and antibiotic resistance data to identify patient-to-patient transmission and development of antibiotic resistance.We found that MALDI-TOF/API N20 was not sufficient for Achromobacter species-level typing, and that the population of Achromobacter isolates was composed of five different species where A. xylosoxidans accounted for 52% of infections. Most patients were infected by unique Achromobacter clone types; nonetheless, suspected patient-to-patient transmission cases identified by shared clone types were observed in 35% (N=18) of patients. In 15 of 16 cases the suspected transmissions were further supported by genome- or clinic visit-based epidemiological analysis. Finally, we found that resistance developed over time.We show that whole-genome sequencing (WGS) is essential for Achromobacter species typing and patient-to-patient transmission identification which was identified in A. ruhlandii, A. xylosoxidans and, for the first time, A. insuavis. Furthermore, we show that the development of antibiotic resistance is associated with chronic Achromobacter infections. Our findings emphasize that transmission and antibiotic resistance should be considered in future treatment strategies.

scholarly journals Lack of Association between Hypermutation and Antibiotic Resistance Development in Pseudomonas aeruginosa Isolates from Intensive Care Unit Patients

2004 ◽  
Vol 48 (9) ◽  
pp. 3573-3575 ◽  
Author(s):  
Olivia Gutiérrez ◽  
Carlos Juan ◽  
José L. Pérez ◽  
Antonio Oliver
Keyword(s):  
Cystic Fibrosis ◽  
Intensive Care Unit ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Intensive Care ◽  
Large Collection ◽  
Resistance Development ◽  
Icu Patients

ABSTRACT Hypermutation is a common feature of Pseudomonas aeruginosa isolates from chronically infected cystic fibrosis patients that is linked with antibiotic resistance development. In this work, using a large collection of sequential P. aeruginosa isolates from ICU patients, we found that despite the fact that mutational antibiotic resistance development is a frequent outcome, the prevalence of hypermutable strains is low (found in isolates from only 1 of 103 patients) and there is no evidence of coselection of the hypermutable and antibiotic resistance phenotypes.

scholarly journals Achromobacter genetic adaptation in cystic fibrosis

2021 ◽  
Author(s):  
Migle Gabrielaite ◽  
Finn C. Nielsen ◽  
Helle K. Johansen ◽  
Rasmus L. Marvig
Keyword(s):  
Cystic Fibrosis ◽  
Antibiotic Resistance ◽  
Ion Transport ◽  
Genome Wide Association Study ◽  
Severe Disease ◽  
Genetic Adaptation ◽  
Emerging Pathogens ◽  
Inorganic Ion ◽  
Gene Enrichment ◽  
Genome Wide

AbstractAchromobacter is an emerging pathogen in patients with cystic fibrosis (CF) and Achromobacter caused infections are associated with more severe disease outcomes and high intrinsic antibiotic resistance. While conventional CF pathogens are studied extensively, little is known about the genetic determinants leading to antibiotic resistance and the genetic adaptation in Achromobacter infections.Here, we analyzed 101 Achromobacter genomes from 51 patients with CF isolated during the course of up to 20 years of infection to identify within-host adaptation, mutational signatures, and genetic variation associated with increased antibiotic resistance.We found that the same regulatory and inorganic ion transport genes were frequently mutated in persisting clone types within and between Achromobacter species indicating convergent genetic adaptation. Genome-wide association study (GWAS) of six antibiotic resistance phenotypes revealed the enrichment of associated genes involved in inorganic ion transport genes, transcription gene enrichment in β-lactams, and energy production and translation gene enrichment in the trimethoprim/sulfonamide group.Overall, we provide insights into the pathogenomics of Achromobacter infections in patients with CF airways. Since emerging pathogens are increasingly recognised as an important healthcare issue, our findings on evolution of antibiotic resistance and genetic adaptation can facilitate better understanding of disease progression and how mutational changes have implications for patients with CF.

scholarly journals Antimicrobial Resistance: Then and Now

2020 ◽  
Vol 2 (02) ◽  
pp. 50-55
Author(s):  
Kanika Sharma ◽  
Baitullah Abdali ◽  
Payal Kesharwani ◽  
Neha Mittal ◽  
Hemlata Bisht
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
20Th Century ◽  
Mechanisms Of Resistance ◽  
Resistance Development ◽  
Development History ◽  
The Past ◽  
Genetic Makeup ◽  
Resistance Data ◽  
Alexander Fleming

Antibiotics have been regarded as one of the major discoveries of the 20th century. But the problem that came attached with is the rise of antibiotic resistance in hospitals and communities. The genetic makeup of microbes has benefitted from man's overuse of antibiotics to exploit every source of resistance genes and means of horizontal gene transmission to give rise to various mechanisms of resistance. Alexander Fleming upon accepting the 1945 Nobel Prize in Medicine said “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them. There is a danger that an ignorant man may easily under dose himself and by exposing his microbes to non lethal quantities of the drug and make them resistant”. This review presents the multifaceted aspects of antibiotic resistance development, history, superbug and superresiatance and resistance data observed over the past years with an overt conclusion showing undeniable methods to overcome the discussed problem, glaringly striking that it is time to act.

scholarly journals A MexR Mutation Which Confers Aztreonam Resistance to Pseudomonas aeruginosa

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhenzhen Ma ◽  
Congjuan Xu ◽  
Xinxin Zhang ◽  
Dan Wang ◽  
Xiaolei Pan ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Clinical Setting ◽  
Gene Editing ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Resistance Development ◽  
Host Environment ◽  
Dna Resequencing ◽  
First Time

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.

scholarly journals Epidemiological Analysis of Sequential Pseudomonas aeruginosa Isolates from Chronic Bronchiectasis Patients without Cystic Fibrosis

1999 ◽  
Vol 37 (6) ◽  
pp. 2071-2073 ◽  
Author(s):  
I. Pujana ◽  
L. Gallego ◽  
G. Martín ◽  
F. López ◽  
J. Canduela ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Genetic Similarity ◽  
Cross Infection ◽  
Major Type ◽  
Common Source ◽  
Epidemiological Investigation ◽  
Epidemiological Analysis ◽  
Pcr Fingerprinting

PCR fingerprinting was used for the epidemiological investigation of 64 Pseudomonas aeruginosa isolates collected from 16 chronic bronchiectasis patients without cystic fibrosis: 56% of the patients harbored one clone, 12.5% carried a single major type with minor variants, and 31.5% carried two clones. Only a minority of the acquisitions of antibiotic resistance was related to the acquisition of exogenous strains. Mucoid and nonmucoid sets of isolates did not display any consistent differences in their patterns. The genetic similarity among the clones ranged from 10 to 69%. Cross-infection or common-source exposure did not appear to have occurred.

scholarly journals Risk factors for antibiotic resistance development in healthcare settings in China: A systematic review

2021 ◽  
pp. 1-30
Author(s):  
Qi Chen ◽  
Duguang Li ◽  
Claudia Beiersmann ◽  
Florian Neuhann ◽  
Babak Moazen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Antibiotic Resistance ◽  
Resistance Development ◽  
Healthcare Settings

scholarly journals Vibrio cholerae Triggers SOS and Mutagenesis in Response to a Wide Range of Antibiotics: a Route towards Multiresistance

2011 ◽  
Vol 55 (5) ◽  
pp. 2438-2441 ◽  
Author(s):  
Zeynep Baharoglu ◽  
Didier Mazel
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Vibrio Cholerae ◽  
Fluorescent Protein ◽  
Resistance Development ◽  
Content Type ◽  
E Coli ◽  
Wide Range ◽  
Green Fluorescent ◽  
Regulated Promoters

ABSTRACTAntibiotic resistance development has been linked to the bacterial SOS stress response. InEscherichia coli, fluoroquinolones are known to induce SOS, whereas other antibiotics, such as aminoglycosides, tetracycline, and chloramphenicol, do not. Here we address whether various antibiotics induce SOS inVibrio cholerae. Reporter green fluorescent protein (GFP) fusions were used to measure the response of SOS-regulated promoters to subinhibitory concentrations of antibiotics. We show that unlike the situation withE. coli, all these antibiotics induce SOS inV. cholerae.

scholarly journals Cancer immunoediting: A game theoretical approach

2020 ◽  
pp. 1-12
Author(s):  
Fatemeh Tavakoli ◽  
Javad Salimi Sartakhti ◽  
Mohammad Hossein Manshaei ◽  
David Basanta
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Evolutionary Game ◽  
Equilibrium Phase ◽  
Tumor Development ◽  
Treatment Strategies ◽  
Cancer Immunoediting ◽  
Proposed Model ◽  
Game Theoretical Approach ◽  
First Time

The role of the immune system in tumor development increasingly includes the idea of cancer immunoediting. It comprises three phases: elimination, equilibrium, and escape. In the first phase, elimination, transformed cells are recognized and destroyed by immune system. The rare tumor cells that are not destroyed in this phase may then enter the equilibrium phase, where their growth is prevented by immunity mechanisms. The escape phase represents the final phase of this process, where cancer cells begin to grow unconstrained by the immune system. In this study, we describe and analyze an evolutionary game theoretical model of proliferating, quiescent, and immune cells interactions for the first time. The proposed model is evaluated with constant and dynamic approaches. Population dynamics and interactions between the immune system and cancer cells are investigated. Stability of equilibria or critical points are analyzed by applying algebraic analysis. This model allows us to understand the process of cancer development and might help us design better treatment strategies to account for immunoediting.

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