scholarly journals Evolutionary instability of collateral susceptibility networks in ciprofloxacin resistant clinical Escherichia coli strains

2021 ◽  
Author(s):  
Vidar Sørum ◽  
Emma L. Øynes ◽  
Anna S. Møller ◽  
Klaus Harms ◽  
Ørjan Samuelsen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Treatment Guidelines ◽  
Acquired Resistance ◽  
Resistance Development ◽  
Compensatory Evolution ◽  
Collateral Sensitivity ◽  
Resistance Determinants ◽  
Main Driver ◽  
Collateral Effects ◽  
Compensatory Mutations

Collateral sensitivity and resistance occur when resistance development towards one antimicrobial either potentiates or deteriorates the effect of others, respectively. Previous reports on collateral effects on susceptibility focus on newly acquired resistance determinants and propose that novel treatment guidelines informed by collateral networks may reduce the evolution, selection and spread of antimicrobial resistance. In this study, we investigate the evolutionary stability of collateral networks in five ciprofloxacin resistant, clinical Escherichia coli strains. After 300 generations of experimental evolution without antimicrobials, we show complete fitness restoration in four of five genetic backgrounds and demonstrate evolutionary instability in collateral networks of newly acquired resistance determinants. We show that compensatory mutations reducing efflux expression is the main driver destabilizing initial collateral networks and identify rpoS as a putative target for compensatory evolution. Our results add another layer of complexity to future predictions and clinical application of collateral networks.

scholarly journals Genetic but No Phenotypic Associations between Biocide Tolerance and Antibiotic Resistance in Escherichia coli from German Broiler Fattening Farms

2021 ◽  
Vol 9 (3) ◽  
pp. 651
Author(s):  
Alice Roedel ◽  
Szilvia Vincze ◽  
Michaela Projahn ◽  
Uwe Roesler ◽  
Caroline Robé ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Acquired Resistance ◽  
Antibiotic Resistance Genes ◽  
Animal Husbandry ◽  
Metal Resistance ◽  
Resistant Bacteria ◽  
Virulence Determinants ◽  
Phylogenetic Distribution ◽  
Resistance Determinants

Biocides are frequently applied as disinfectants in animal husbandry to prevent the transmission of drug-resistant bacteria and to control zoonotic diseases. Concerns have been raised, that their use may contribute to the selection and persistence of antimicrobial-resistant bacteria. Especially, extended-spectrum β-lactamase- and AmpC β-lactamase-producing Escherichia coli have become a global health threat. In our study, 29 ESBL-/AmpC-producing and 64 NON-ESBL-/AmpC-producing E.coli isolates from three German broiler fattening farms collected in 2016 following regular cleaning and disinfection were phylogenetically characterized by whole genome sequencing, analyzed for phylogenetic distribution of virulence-associated genes, and screened for determinants of and associations between biocide tolerance and antibiotic resistance. Of the 30 known and two unknown sequence types detected, ST117 and ST297 were the most common genotypes. These STs are recognized worldwide as pandemic lineages causing disease in humans and poultry. Virulence determinants associated with extraintestinal pathogenic E.coli showed variable phylogenetic distribution patterns. Isolates with reduced biocide susceptibility were rarely found on the tested farms. Nine isolates displayed elevated MICs and/or MBCs of formaldehyde, chlorocresol, peroxyacetic acid, or benzalkonium chloride. Antibiotic resistance to ampicillin, trimethoprim, and sulfamethoxazole was most prevalent. The majority of ESBL-/AmpC-producing isolates carried blaCTX-M (55%) or blaCMY-2 (24%) genes. Phenotypic biocide tolerance and antibiotic resistance were not interlinked. However, biocide and metal resistance determinants were found on mobile genetic elements together with antibiotic resistance genes raising concerns that biocides used in the food industry may lead to selection pressure for strains carrying acquired resistance determinants to different antimicrobials.

scholarly journals Compensatory Evolution in Rifampin-Resistant Escherichia coli

Genetics ◽  
2000 ◽  
Vol 156 (4) ◽  
pp. 1471-1481 ◽  
Author(s):  
Mary G Reynolds
Keyword(s):  
Escherichia Coli ◽  
Parallel Evolution ◽  
Clinical Problem ◽  
Relative Fitness ◽  
Serial Transfer ◽  
Compensatory Evolution ◽  
Rifampin Resistance ◽  
Compensatory Mutations ◽  
High Level ◽  
The Cost

Abstract This study examines the intrinsic fitness burden associated with RNA polymerase (rpoB) mutations conferring rifampin resistance in Escherichia coli K12 (MG1655) and explores the nature of adaptation to the costs of resistance. Among 28 independent Rifr mutants, the per-generation fitness burden (in the absence of rifampin) ranged from 0 to 28%, with a median of 6.4%. We detected no relationship between the magnitude of the cost and the level of resistance. Adaptation to the costs of rif resistance was studied by following serial transfer cultures for several Rifr mutants both in the presence of rifampin and in the absence. For cultures evolved in the absence of rifampin, single clones isolated after 200 generations were more fit than their ancestor; we saw no association between increased fitness and changes in the level of rifampin resistance; and in all cases, increased fitness was due to compensatory mutations, rather than to reversion to drug sensitivity. However, in the parallel evolution experiments in the presence of rifampin, overall levels of resistance increased as did relative fitness—for all strains save one that had an initially high level of resistance. Among the evolved clones tested, five (of seven) demonstrated increased transcription efficiency (assessed using a semiquantitative RT-PCR protocol). The implications of these results for our understanding of adaptive molecular evolution and the increasing clinical problem of antibiotic resistance are discussed.

scholarly journals Collateral sensitivity interactions between antibiotics depend on local abiotic conditions

2020 ◽  
Author(s):  
Richard C. Allen ◽  
Katia R. Pfrunder-Cardozo ◽  
Alex R. Hall
Keyword(s):  
Escherichia Coli ◽  
Real World ◽  
Cross Resistance ◽  
Local Conditions ◽  
Abiotic Conditions ◽  
Collateral Sensitivity ◽  
Resistance Evolution ◽  
Real World Applications ◽  
Collateral Effects ◽  
Resistant Mutants

AbstractMutations conferring resistance to one antibiotic can increase (cross resistance) or decrease (collateral sensitivity) resistance to others. Drug combinations displaying collateral sensitivity could be used in treatments that slow resistance evolution. However, lab-to-clinic translation requires understanding whether collateral effects are robust across different environmental conditions. Here, we isolated and characterized resistant mutants of Escherichia coli using five antibiotics, before measuring collateral effects on resistance to other antibiotics. During both isolation and phenotyping, we varied conditions in ways relevant in nature (pH, temperature, bile). This revealed local abiotic conditions modified expression of resistance against both the antibiotic used during isolation and other antibiotics. Consequently, local conditions influenced collateral sensitivity in two ways: by favouring different sets of mutants (with different collateral sensitivities), and by modifying expression of collateral effects for individual mutants. These results place collateral sensitivity in the context of environmental variation, with important implications for translation to real-world applications.

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 Resistance Mechanisms of Multiresistant Pseudomonas aeruginosa Strains from Germany and Correlation with Hypermutation

2007 ◽  
Vol 51 (11) ◽  
pp. 4062-4070 ◽  
Author(s):  
B. Henrichfreise ◽  
I. Wiegand ◽  
W. Pfister ◽  
B. Wiedemann
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Type Ii ◽  
Mechanisms Of Resistance ◽  
Resistance Determinants ◽  
Class 1 ◽  
Mutator Strains ◽  
Multiresistant Strains

ABSTRACT In this study, we analyzed the mechanisms of multiresistance for 22 clinical multiresistant and clonally different Pseudomonas aeruginosa strains from Germany. Twelve and 10 strains originated from cystic fibrosis (CF) and non-CF patients, respectively. Overproduction of the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was studied. Furthermore, loss of OprD, alterations in type II topoisomerases, AmpC overproduction, and the presence of 25 acquired resistance determinants were investigated. The presence of a hypermutation phenotype was also taken into account. Besides modifications in GyrA (91%), the most frequent mechanisms of resistance were MexXY-OprM overproduction (82%), OprD loss (82%), and AmpC overproduction (73%). Clear differences between strains from CF and non-CF patients were found: numerous genes coding for aminoglycoside-modifying enzymes and located, partially in combination with β-lactamase genes, in class 1 integrons were found only in strains from non-CF patients. Furthermore, multiple modifications in type II topoisomerases conferring high quinolone resistance levels and overexpression of MexAB-OprM were exclusively detected in multiresistant strains from non-CF patients. Correlations of the detected phenotypes and resistance mechanisms revealed a great impact of efflux pump overproduction on multiresistance in P. aeruginosa. Confirming previous studies, we found that additional, unknown chromosomally mediated resistance mechanisms remain to be determined. In our study, 11 out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable. This extremely high proportion of mutator strains should be taken into consideration for the treatment of multiresistant P. aeruginosa.

scholarly journals Impact of Feed Supplementation with Antimicrobial Agents on Growth Performance of Broiler Chickens, Clostridium perfringens and Enterococcus Counts, and Antibiotic Resistance Phenotypes and Distribution of Antimicrobial Resistance Determinants in Escherichia coli Isolates

2007 ◽  
Vol 73 (20) ◽  
pp. 6566-6576 ◽  
Author(s):  
Moussa S. Diarra ◽  
Fred G. Silversides ◽  
Fatoumata Diarrassouba ◽  
Jane Pritchard ◽  
Luke Masson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Broiler Chickens ◽  
Antimicrobial Agents ◽  
Growth Promoters ◽  
Feed Supplementation ◽  
E Coli ◽  
Resistance Determinants ◽  
Class 1

ABSTRACT The effects of feed supplementation with the approved antimicrobial agents bambermycin, penicillin, salinomycin, and bacitracin or a combination of salinomycin plus bacitracin were evaluated for the incidence and distribution of antibiotic resistance in 197 commensal Escherichia coli isolates from broiler chickens over 35 days. All isolates showed some degree of multiple antibiotic resistance. Resistance to tetracycline (68.5%), amoxicillin (61.4%), ceftiofur (51.3%), spectinomycin (47.2%), and sulfonamides (42%) was most frequent. The levels of resistance to streptomycin, chloramphenicol, and gentamicin were 33.5, 35.5, and 25.3%, respectively. The overall resistance levels decreased from day 7 to day 35 (P < 0.001). Comparing treatments, the levels of resistance to ceftiofur, spectinomycin, and gentamicin (except for resistance to bacitracin treatment) were significantly higher in isolates from chickens receiving feed supplemented with salinomycin than from the other feeds (P < 0.001). Using a DNA microarray analysis capable of detecting commonly found antimicrobial resistance genes, we characterized 104 tetracycline-resistant E. coli isolates from 7- to 28-day-old chickens fed different growth promoters. Results showed a decrease in the incidence of isolates harboring tet(B), bla TEM, sulI, and aadA and class 1 integron from days 7 to 35 (P < 0.01). Of the 84 tetracycline-ceftiofur-resistant E. coli isolates, 76 (90.5%) were positive for bla CMY-2. The proportions of isolates positive for sulI, aadA, and integron class 1 were significantly higher in salinomycin-treated chickens than in the control or other treatment groups (P < 0.05). These data demonstrate that multiantibiotic-resistant E. coli isolates can be found in broiler chickens regardless of the antimicrobial growth promoters used. However, the phenotype and the distribution of resistance determinants in E. coli can be modulated by feed supplementation with some of the antimicrobial agents used in broiler chicken production.

scholarly journals Extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing Escherichia coli isolates causing bacteremia in the Netherlands (2014 – 2016) differ in clonal distribution, antimicrobial resistance gene and virulence gene content

2019 ◽  
Author(s):  
Denise van Hout ◽  
Tess D. Verschuuren ◽  
Patricia C.J. Bruijning-Verhagen ◽  
Thijs Bosch ◽  
Anita C. Schürch ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
The Netherlands ◽  
Resistance Gene ◽  
Acquired Resistance ◽  
Virulence Gene ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
Clonal Distribution

ABSTRACTBackgroundKnowledge on the molecular epidemiology of Escherichia coli causing E. coli bacteremia (ECB) in the Netherlands is mostly based on extended-spectrum beta-lactamase-producing E. coli (ESBL-Ec). We determined differences in clonality and resistance and virulence gene (VG) content between non-ESBL-producing E. coli (non-ESBL-Ec) and ESBL-Ec blood isolates with different epidemiological characteristics.Materials/methodsA random selection of non-ESBL-Ec isolates as well as all available ESBL-Ec blood isolates was obtained from two Dutch hospitals between 2014 and 2016. Whole genome sequencing was performed to infer sequence types (STs), serotypes, acquired antibiotic resistance genes and VG scores, based on presence of 49 predefined putative pathogenic VG.ResultsST73 was most prevalent among the 212 non-ESBL-Ec (N=26, 12.3%) and ST131 among the 69 ESBL-Ec (N=30, 43.5%). Prevalence of ST131 among non-ESBL-Ec was 10.4% (N=22, P value < 0.001 compared to ESBL-Ec). O25:H4 was the most common serotype in both non-ESBL-Ec and ESBL-Ec. Median acquired resistance gene counts were 1 (IQR 1 – 6) and 7 (IQR 4 – 9) for non-ESBL-Ec and ESBL-Ec, respectively (P value < 0.001). Among non-ESBL-Ec, acquired resistance gene count was highest among blood isolates from a primary gastro-intestinal focus (median 4, IQR 1 – 8). Median VG scores were 13 (IQR 9 – 20) and 12 (IQR 8 – 14) for non-ESBL-Ec and ESBL-Ec, respectively (P value = 0.002). VG scores among non-ESBL-Ec from a primary urinary focus (median 15, IQR 11 – 21) were higher compared to non-ESBL-Ec from a primary gastro-intestinal (median 10, IQR 6 – 13) or hepatic-biliary focus (median 11, IQR 5 – 18) (P values = 0.007 and 0.036, respectively). VG content varied between different E. coli STs.ConclusionsNon-ESBL-Ec and ESBL-Ec blood isolates from two Dutch hospitals differed in clonal distribution, resistance gene and VG content. Also, resistance gene and VG content differed between non-ESBL-Ec from different primary foci of ECB.

scholarly journals mSphere of Influence: Evolutionary Strategies To Sensitize Drug-Resistant Pathogens

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Rebecca S. Shapiro
Keyword(s):  
Drug Resistance ◽  
Antimicrobial Resistance ◽  
Genetic Interaction ◽  
Interaction Networks ◽  
Evolutionary Strategies ◽  
Drug Resistant ◽  
Bacterial Evolution ◽  
Resistance Development ◽  
Collateral Sensitivity ◽  
Link Type

ABSTRACTRebecca S. Shapiro studies antimicrobial resistance and genetic interaction networks. In this mSphere of Influence article, she reflects on how the papers “Bacterial evolution of antibiotic hypersensitivity” by Lázár et al. (V. Lázár, G. Pal Singh, R. Spohn, I. Nagy, et al., Mol Syst Biol 9:700, 2013,https://doi.org/10.1038/msb.2013.57) and “Use of collateral sensitivity networks to design drug cycling protocols that avoid resistance development” by L. Imamovic and M. O. A. Sommer (Sci Transl Med 5:204ra132, 2013,https://doi.org/10.1126/scitranslmed.3006609) impacted her thinking about multigene interaction effects on drug resistance.

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