Co-occurrence of aminoglycoside and β-lactam resistance mechanisms in aminoglycoside- non-susceptible Escherichia coli isolated in the Zurich area, Switzerland

Bodendoerfer, Elias; Marchesi, Martina; Imkamp, Frank; Courvalin, Patrice; Böttger, Erik C.; Mancini, Stefano

doi:10.1016/j.ijantimicag.2020.106019

Cited by 29 publications

(41 citation statements)

References 39 publications

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“…The variations in results of the prevalent ESBL types might be attributed to differences in sampling period and geographical locations (Vital et al 2018). Aminoglycosides are antibiotics that are frequently used in combination with β-lactams for the treatment of gram-negative bacterial infections (Bodendoerfer et al 2020). One mechanism of resistance of aminoglycosides involves the formation of enzymes, which modify the antibiotic drug at various sites (Bodendoerfer et al 2020;Schaenzer & Wright 2020).…”

Section: Resultsmentioning

confidence: 99%

“…Aminoglycosides are antibiotics that are frequently used in combination with β-lactams for the treatment of gram-negative bacterial infections (Bodendoerfer et al 2020). One mechanism of resistance of aminoglycosides involves the formation of enzymes, which modify the antibiotic drug at various sites (Bodendoerfer et al 2020;Schaenzer & Wright 2020). The strA gene is one of the resistance genes that encode aminoglycoside-modifying enzyme, which confers resistance to streptomycin (Frye & Jackson 2013;Poirel et al 2018).…”

Section: Resultsmentioning

confidence: 99%

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Predominance of blaTEM and tetA genes in antibiotic-resistant Escherichia coli isolates from Laguna Lake, Philippines

Salvador-Membreve

Rivera

2021

Journal of Water, Sanitation and Hygiene for Development

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Lakes are one of the sinks of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs); however, information on ARB and ARGs in lakes in the Philippines is scarce. In this study, Escherichia coli was isolated from the largest freshwater lake in the Philippines, Laguna Lake, to detect antibiotic resistance and the presence of ARGs. Broth microdilution assay (BMA) and molecular identification of five environmentally prevalent ARGs (strA, blaCTX-M, blaSHV, blaTEM, and tetA) were performed. The majority (75.70%) of the isolates harbored at least one of the targeted antibiotic genes. Multiplex PCR detected about 49.07% of the isolates had genes for extended-spectrum β-lactamases (ESBL), which were mostly represented by blaTEM (47.66%). The genes strA and tetA were observed in this study with detection frequencies of 29.91 and 45.33%, respectively. About 95.69% of thermotolerant E. coli isolates were non-susceptible to six different antibiotics using BMA. Nearly 37% of the isolates were found to be multidrug-resistant (MDR) with most isolates resistant to ampicillin (81.72%). Furthermore, the occurrence of ESBL genes was significantly correlated with tetA genes (P = 0.013). To date, this study is the first to report on the presence of MDR and thermotolerant E. coli in Laguna Lake, Philippines.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Predominance of blaTEM and tetA genes in antibiotic-resistant Escherichia coli isolates from Laguna Lake, Philippines

Salvador-Membreve

Rivera

2021

Journal of Water, Sanitation and Hygiene for Development

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“…In contrast, susceptibility to standard-of-care aminoglycosides was lower, at <97% and <79%, respectively, when based on RMTase gene annotations alone and not taking into account the high number of aminoglycoside-modifying enzymes that inactivate the various standard-of-care aminoglycosides but not apramycin. The higher levels of aminoglycoside resistance in CP isolates might not be surprising, given the frequent co-occurrence of different resistance genes, including that of RMTases with carbapenemases [ 6 , 30 , 31 , 32 ]. Of note, we did not detect any aac(3)-IV genes in the critical pathogen populations of carbapenem-resistant A. baumannii and Pseudomonas aeruginosa .…”

Section: Discussionmentioning

confidence: 99%

Epidemiologic, Phenotypic, and Structural Characterization of Aminoglycoside-Resistance Gene aac(3)-IV

Plattner

Gysin

Haldimann

et al. 2020

IJMS

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Aminoglycoside antibiotics are powerful bactericidal therapeutics that are often used in the treatment of critical Gram-negative systemic infections. The emergence and global spread of antibiotic resistance, however, has compromised the clinical utility of aminoglycosides to an extent similar to that found for all other antibiotic-drug classes. Apramycin, a drug candidate currently in clinical development, was suggested as a next-generation aminoglycoside antibiotic with minimal cross-resistance to all other standard-of-care aminoglycosides. Here, we analyzed 591,140 pathogen genomes deposited in the NCBI National Database of Antibiotic Resistant Organisms (NDARO) for annotations of apramycin-resistance genes, and compared them to the genotypic prevalence of carbapenem resistance and 16S-rRNA methyltransferase (RMTase) genes. The 3-N-acetyltransferase gene aac(3)-IV was found to be the only apramycin-resistance gene of clinical relevance, at an average prevalence of 0.7%, which was four-fold lower than that of RMTase genes. In the important subpopulation of carbapenemase-positive isolates, aac(3)-IV was nine-fold less prevalent than RMTase genes. The phenotypic profiling of selected clinical isolates and recombinant strains expressing the aac(3)-IV gene confirmed resistance to not only apramycin, but also gentamicin, tobramycin, and paromomycin. Probing the structure–activity relationship of such substrate promiscuity by site-directed mutagenesis of the aminoglycoside-binding pocket in the acetyltransferase AAC(3)-IV revealed the molecular contacts to His124, Glu185, and Asp187 to be equally critical in binding to apramycin and gentamicin, whereas Asp67 was found to be a discriminating contact. Our findings suggest that aminoglycoside cross-resistance to apramycin in clinical isolates is limited to the substrate promiscuity of a single gene, rendering apramycin best-in-class for the coverage of carbapenem- and aminoglycoside-resistant bacterial infections.

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“…Furthermore, 76 strains (63.3%; 76/120) carried bla OXA−1 and eight (6.7%; 8/120) bla CTX−M−27 . Previous studies reported the co-occurrence of bla CTX−M−15 and bla OXA−1 , whereas other members of the CTX-M family (e.g., bla CTX−M−27 ) and bla OXA−1 appear to be mutually exclusive (Schaufler et al, 2016b;Livermore et al, 2019;Bodendoerfer et al, 2020). Here, almost all strains carrying the bla OXA−1 gene (98.7%; 75/76) carried the bla CTX−M−15 gene in addition and none showed the combination of bla OXA−1 and another CTX-M gene.…”

Section: Antimicrobial Resistance Determinantsmentioning

confidence: 96%

Circulation of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli of Pandemic Sequence Types 131, 648, and 410 Among Hospitalized Patients, Caregivers, and the Community in Rwanda

et al. 2021

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Multi-drug resistant (MDR), gram-negative Enterobacteriaceae, such as Escherichia coli (E. coli) limit therapeutic options and increase morbidity, mortality, and treatment costs worldwide. They pose a serious burden on healthcare systems, especially in developing countries like Rwanda. Several studies have shown the effects caused by the global spread of extended-spectrum beta-lactamase (ESBL)-producing E. coli. However, limited data is available on transmission dynamics of these pathogens and the mobile elements they carry in the context of clinical and community locations in Sub-Saharan Africa. Here, we examined 120 ESBL-producing E. coli strains from patients hospitalized in the University Teaching Hospital of Butare (Rwanda), their attending caregivers as well as associated community members and livestock. Based on whole-genome analysis, the genetic diversification and phylogenetics were assessed. Moreover, the content of carried plasmids was characterized and investigated for putative transmission among strains, and for their potential role as drivers for the spread of antibiotic resistance. We show that among the 30 different sequence types (ST) detected were the pandemic clonal lineages ST131, ST648 and ST410, which combine high-level antimicrobial resistance with virulence. In addition to the frequently found resistance genes blaCTX–M–15, tet(34), and aph(6)-Id, we identified csg genes, which are required for curli fiber synthesis and thus biofilm formation. Numerous strains harbored multiple virulence-associated genes (VAGs) including pap (P fimbriae adhesion cluster), fim (type I fimbriae) and chu (Chu heme uptake system). Furthermore, we found phylogenetic relationships among strains from patients and their caregivers or related community members and animals, which indicates transmission of pathogens. Also, we demonstrated the presence and potential transfer of identical/similar ESBL-plasmids in different strains from the Rwandan setting and when compared to an external plasmid. This study highlights the circulation of clinically relevant, pathogenic ESBL-producing E. coli among patients, caregivers and the community in Rwanda. Combining antimicrobial resistance with virulence in addition to the putative exchange of mobile genetic elements among bacterial pathogens poses a significant risk around the world.

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Co-occurrence of aminoglycoside and β-lactam resistance mechanisms in aminoglycoside- non-susceptible Escherichia coli isolated in the Zurich area, Switzerland

Cited by 29 publications

References 39 publications

Predominance of blaTEM and tetA genes in antibiotic-resistant Escherichia coli isolates from Laguna Lake, Philippines

Predominance of blaTEM and tetA genes in antibiotic-resistant Escherichia coli isolates from Laguna Lake, Philippines

Epidemiologic, Phenotypic, and Structural Characterization of Aminoglycoside-Resistance Gene aac(3)-IV

Circulation of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli of Pandemic Sequence Types 131, 648, and 410 Among Hospitalized Patients, Caregivers, and the Community in Rwanda

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