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![The most common aminoglycoside- modifying enzymes in this study and their respective spectra of activity [ 1 , 8 ]](publication/341415074/figure/tbl2/AS:902754549645313@1592244865558/The-most-common-aminoglycoside-modifying-enzymes-in-this-study-and-their-respective.png)
The most common aminoglycoside- modifying enzymes in this study and their respective spectra of activity [ 1 , 8 ]
Source publication
We here assessed the co-occurrence of aminoglycoside and β-lactam resistance in 3358 consecutive Escherichia coli clinical isolates collected in 2014 in the greater Zurich area, Switzerland. Non-susceptibility to at least one of the tested aminoglycosides was observed in 470/3358 E. coli strains (14%). In strains categorized as broad spectrum β-lac...
Contexts in source publication
Context 1
... 2 shows the co-occurrence of aminoglycoside and β-lactam resistance genes in 424 strains classified as β-lactam wild-type, or BSBL-or ESBL-producers (Fisher's exact test P = 0.0 0 04998). Based on genotypic data, the isolates were grouped by aminoglycoside resistance mechanism conferring the same inferred resistance phenotype ( Table 3 ). Thus, all strains only carrying an aph(3') gene were classified as kanamycin-resistant [34] . ...Context 2
... determine whether clonal spread is involved in the cooccurrence of resistance described, the sequence types (STs) of the E. coli genomes were analysed. This revealed a wide diversity of 76 STs (Table S3). The most abundant, ST131, was found in 124 strains associated with several β-lactam and aminoglycoside resistance genes. ...Similar publications
Background
The increase in multidrug resistance (MDR) among pathogenic bacteria responsible for infectious diseases has led to lack of effectiveness of some antibiotics. The ability of Escherichia coli to harbor resistant genes has made the treatment of infections a major challenge. This study was carried out to assess antibiotic resistance and ext...
Significance
A fundamental question in evolution is the repeatability of adaptation. Will independently evolving populations respond similarly when facing the same environmental challenge? This question also has important public-health implications related to the growing problem of antibiotic resistance. For example, efforts to control resistance m...
Antibiotic resistance is a growing concern that has prompted a renewed focus on drug discovery, stewardship, and evolutionary studies of the patterns and processes that underlie this phenomenon. A resistant strain's competitive fitness relative to its sensitive counterparts in the absence of drug can impact its spread and persistence in both clinic...
The antibiotic trimethoprim (TMP) is used to treat a variety of Escherichia coli infections, but its efficacy is limited by the rapid emergence of TMP-resistant bacteria. Previous laboratory evolution experiments have identified resistance-conferring mutations in the gene encoding the TMP target, bacterial dihydrofolate reductase (DHFR), in particu...
A total of 292 E. coli isolates obtained from fecal samples from pigs in Central (n = 103) and Northeastern (n = 189) provinces of Thailand were included in this study. Eighty-six E. coli isolates were phenotypically confirmed to be β-lactamases producers and screened for the presence of β-lactamase genes. The CTX-M family was most frequently ident...
Citations
... MDR strains utilize various resistance mechanisms that pose challenges to the efficacy of existing antibiotic treatments. Beta-lactamases and aminoglycoside-modifying enzymes are prevalent mechanisms that confer resistance to beta-lactam antibiotics and aminoglycosides, respectively [5,6]. Beta-lactamases, such as extended-spectrum beta-lactamases (ESBLs) and carbapenemases, hydrolyze beta-lactam rings, rendering antibiotics ineffective [7]. ...
The current healthcare environment is at risk due to the facilitated transmission and empowerment of the ESKAPE pathogens, comprising of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. These pathogens have posed significant challenges to global public health and the threat has only amplified over time. These multidrug-resistant bacteria have become adept at escaping the effects of conventional antibiotics utilized, leading to severe healthcare-associated infections and compromising immunocompromised patient outcomes to a greater extent. The impact of ESKAPE pathogens is evident in the rapidly rising rates of treatment failures, increased mortality, and elevated healthcare costs. To combat this looming crisis, diverse strategies have been adopted, ranging from the development of novel antimicrobial agents and combination therapies to the implementation of stringent infection control measures. Additionally, there has been a growing emphasis on promoting antimicrobial stewardship programs to optimize the use of existing antibiotics and reduce the selective pressure driving the evolution of resistance. While progress has been made to some extent, the rapid adaptability of these pathogens and the enhancement of antimicrobial resistance mechanisms proves to be a major hurdle yet to be crossed by healthcare professionals. In this viewpoint, the impending threat heralded by the proliferation of ESKAPE pathogens, and the need for a concerted global effort via international collaborations for the assurance of effective and sustainable solutions, are explored. To curb the possibility of outbreaks in the future and to safeguard public health, better preparation via global awareness and defense mechanisms should be given paramount importance.
... Quinolone resistance was only correlated with resistance to aminoglycosides (0.29), which is supported by the findings that quinolone resistance was conferred by chromosomal mutations in gyrA, parC, and parE, in addition to a few strains that also possessed aac(6′)-1b-cr ( Fig. 3 and 4). Other groups have found a relationship between the acquisition of ESBL genes and those encoding aminoglycoside-modifying enzymes (82)(83)(84); however, this was not observed here (Fig. 2D, E, 3 and 4; Fig. S1). ...
Antimicrobial resistance (AMR) is an ever-present threat to the treatment of infectious diseases. However, the potential relevance of this phenomenon in environmental reservoirs still raises many questions. Detection of antimicrobial-resistant bacteria in the environment is a critical aspect for understanding the prevalence of resistance outside of clinical settings, as detection in the environment indicates that resistance is likely already widespread. We isolated antimicrobial-resistant Escherichia coli from three urban waterbodies over a 15-month time series, determined their antimicrobial susceptibilities, investigated their population structure, and identified genetic determinants of resistance. We found that E. coli populations at each site were composed of different dominant phylotypes and showed distinct patterns of antimicrobial and multidrug resistance, despite close geographic proximity. Many strains that were genome-sequenced belonged to sequence types of international concern, particularly the ST131 clonal complex. We found widespread resistance to clinically important antimicrobials such as amoxicillin, cefotaxime, and ciprofloxacin, but found that all strains were susceptible to amikacin and the last-line antimicrobials meropenem and fosfomycin. Resistance was most often due to acquirable antimicrobial resistance genes, while chromosomal mutations in gyrA, parC, and parE conferred resistance to quinolones. Whole-genome analysis of a subset of strains further revealed the diversity of the population of E. coli present, with a wide array of AMR and virulence genes identified, many of which were present on the chromosome, including blaCTX-M. Finally, we determined that environmental persistence, transmission between sites, most likely mediated by wild birds, and transfer of mobile genetic elements likely contributed significantly to the patterns observed.
IMPORTANCE
A One Health perspective is crucial to understand the extent of antimicrobial resistance (AMR) globally, and investigation of AMR in the environment has been increasing in recent years. However, most studies have focused on waterways that are directly polluted by sewage, industrial manufacturing, or agricultural activities. Therefore, there remains a lack of knowledge about more natural, less overtly impacted environments. Through phenotypic and genotypic investigation of AMR in Escherichia coli, this study adds to our understanding of the extent and patterns of resistance in these types of environments, including over a time series, and showed that complex biotic and abiotic factors contribute to the patterns observed. Our study further emphasizes the importance of incorporating the surveillance of microbes in freshwater environments in order to better comprehend potential risks for both human and animal health and how the environment may serve as a sentinel for potential future clinical infections.
... The frequent occurrence of combined resistance genes against different antibiotic groups already indicates the presence of several different plasmids and is confirmed by the finding of various different and multiple replicons, even in closely related isolates. Combinations of β-lactamases and aminoglycoside resistance genes, which have already been described as frequent combinations of antibiotic group resistance [49], were particularly common. ...
The spread of multidrug-resistant bacteria from humans or livestock is a critical issue. However, the epidemiology of resistant pathogens across wastewater pathways is poorly understood. Therefore, we performed a detailed comparison of third-generation cephalosporin-resistant Escherichia coli (3GCREC) from wastewater treatment plants (WWTPs) to analyze dissemination pathways. A total of 172 3GCREC isolated from four WWTPs were characterized via whole genome sequencing. Clonal relatedness was determined using multi-locus sequence typing (MLST) and core genome MLST. Resistance genotypes and plasmid replicons were determined. A total of 68 MLST sequence types were observed with 28 closely related clusters. Resistance genes to eight antibiotic classes were detected. In fluoroquinolone-resistant isolates, resistance was associated with three-or-more point mutations in target genes. Typing revealed high genetic diversity with only a few clonal lineages present in all WWTPs. The distribution paths of individual lines could only be traced in exceptional cases with a lack of enrichment of certain lineages. Varying resistance genes and plasmids, as well as fluoroquinolone resistance-associated point mutations in individual isolates, further corroborated the high diversity of 3GCREC in WWTPs. In total, we observed high diversity of 3GCREC inside the tested WWTPs with proof of resistant strains being released into the environment even after treatment processes.
... Four variants of AMEs were detected in the U7 isolate [aac(3')-IIa, aac(6')-Ib-cr, aph(3'')-Ib, aph(6)-Id)]. The aac(6')-Ib-cr determinant has been found as the most prevalent gene in E. coli from clinical samples and is commonly associated with blaCTX-M-15 and blaOXA-1 [66][67][68]. This association was found for UTI-U7, which exhibited resistance to gentamicin, ciprofloxacin, and norfloxacin. ...
Uropathogenic Escherichia coli (UPEC) is the most common bacterial agent associated with urinary tract infections, threatening public health systems with elevated medical costs and high morbidity rates. The successful establishment of the infection is associated with virulence factors encoded in its genome, in addition to antibacterial resistance genes, which could limit the treatment and resolution of the infection. In this sense, plant extracts from the genus Echeveria have traditionally been used to treat diverse infectious diseases. However, little is known about the effects of these extracts on bacteria and their potential mechanisms of action. This study aims to sequence a multidrug-resistant UPEC isolate (UTI-U7) and assess the multilocus sequence typing (MLST), virulence factors, antimicrobial resistance profile, genes, serotype, and plasmid content. Antimicrobial susceptibility profiling was performed using the Kirby-Bauer disk diffusion. The antibacterial and anti-adherent effects of the methanol extracts (ME) of Echeveria (E. craigiana, E. kimnachii, and E. subrigida) against UTI-U7 were determined. The isolate was characterized as an O25:H4-B2-ST2279-CH40 subclone and had resistant determinants to aminoglycosides, β-lactams, fluoroquinolones/quinolones, amphenicols, and tetracyclines, which matched with the antimicrobial resistance profile. The virulence genes identified encode adherence factors, iron uptake, protectins/serum resistance, and toxins. Identified plasmids belonged to the IncF group (IncFIA, IncFIB, and IncFII), alongside several prophage-like elements. After an extensive genome analysis that confirmed the pathogenic status of UTI-U7 isolate, Echeveria extracts were tested to determine their antibacterial effects; as an extract, E. subrigida (MIC, 5 mg/mL) displayed the best inhibitory effect. However, the adherence between UTI-U7 and HeLa cells was unaffected by the ME of the E. subrigida extract.
... Resistance to quinolones is principally mediated by mutations in the chromosomal quinolone resistance determining region (QRDR), but may also be plasmid-mediated by qnr, aac(6′)-Ib-cr, and genes for various efflux pumps (PMQR). Although PMQR genes alone confer clinically irrelevant levels of resistance, they may indirectly influence the selection of strains with high levels of resistance [60][61][62][63]. In this study, half of the isolates (52%) were found to harbor aac(6')-Ib-cr, eight (1.6%) harbored aac(6')-Ib, and only 18 (3.7%) ...
... bla CTX-M-15 ), variable resistance to aminoglycosides (aac(6')-Ib-cr), and low-level resistance to ciprofloxacin. Intermediate ciprofloxacin resistance can also be detected in strains with both qnrS and aac(6')-Ib-cr genes [60][61][62][63]. In the current study, a combination of aac(6')-Ib-cr and qnrS was detected in only four isolates, two of which also harbored group 1 bla CTX-M genes. ...
Background
Antibiotic resistance is one of the most serious global health problems and threatens the effective treatment of bacterial infections. Of greatest concern are infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC). The aim of our study was to evaluate the prevalence and molecular characteristics of ESBL-EC isolated over an 18-year pre-COVID period from lower respiratory tract (LRT) samples collected from selected Slovenian hospitals.
Objectives and methods
All isolates were identified by MALDI-TOF and phenotypically confirmed as ESBLs by a disk diffusion assay. Using a PCR approach, 487 non-repetitive isolates were assigned to phylogroups, sequence type groups, and clonal groups. Isolates were also screened for virulence-associated genes (VAGs) and antimicrobial resistance genes.
Results
The prevalence of ESBL-EC isolates from LRT in a large university hospital was low (1.4%) in 2005 and increased to 10.8% by 2019. The resistance profile of 487 non-repetitive isolates included in the study showed a high frequency of group 1 blaCTX-M (77.4%; n = 377), blaTEM (54.4%; n = 265) and aac(6')-Ib-cr (52%; n = 253) genes and a low proportion of blaSHV and qnr genes. Isolates were predominantly assigned to phylogroup B2 (73.1%; n = 356), which was significantly associated with clonal group ST131. The ST131 group accounted for 67.6% (n = 329) of all isolates and had a higher number of virulence factor genes than the non-ST131 group. The virulence gene profile of ST131 was consistent with that of other extraintestinal pathogenic E. coli (ExPEC) strains and was significantly associated with ten of sixteen virulence factor genes tested. Using ERIC-PCR fingerprinting, isolates with the same ERIC-profile in samples from different patients, and at different locations and sampling dates were confirmed, indicating the presence of “hospital-adapted” strains.
Conclusion
Our results suggest that the ESBL-EC isolates from LRT do not represent a specific pathotype, but rather resemble other ExPEC isolates, and may be adapted to the hospital environment. To our knowledge, this is the first study of ESBL-EC isolated from LRT samples collected over a long period of time.
... , 2 0 2 1 ) . T r e a t m e n t a g a i n s t Enterobacteriaceae include several families of antibiotics, notably fluoroquinolones and aminoglycosides and understanding the mechanisms of bacterial resistance to these antibiotics is of primary importance (Krause et al., 2016;World Health Organization, 2019;Bodendoerfer et al., 2020;Zhu et al., 2020). Additional drivers can also promote the emergence and propagation of AMR in interconnected environments (Aslam et al., 2021), highlighting the importance of identifying these factors and understanding their actual role in AMR. ...
Antimicrobial resistance is a critical public health issue that requires a thorough understanding of the factors that influence the selection and spread of antibiotic-resistant bacteria. Biocides, which are widely used in cleaning and disinfection procedures in a variety of settings, may contribute to this resistance by inducing similar defense mechanisms in bacteria against both biocides and antibiotics. However, the strategies used by bacteria to adapt and develop cross-resistance remain poorly understood, particularly within biofilms –a widespread bacterial habitat that significantly influences bacterial tolerance and adaptive strategies. Using a combination of adaptive laboratory evolution experiments, genomic and RT-qPCR analyses, and biofilm structural characterization using confocal microscopy, we investigated in this study how Escherichia coli biofilms adapted after 28 days of exposure to three biocidal active substances and the effects on cross-resistance to antibiotics. Interestingly, polyhexamethylene biguanide (PHMB) exposure led to an increase of gentamicin resistance (GenR) phenotypes in biofilms formed by most of the seven E. coli strains tested. Nevertheless, most variants that emerged under biocidal conditions did not retain the GenR phenotype after removal of antimicrobial stress, suggesting a transient adaptation (adaptive resistance). The whole genome sequencing of variants with stable GenR phenotypes revealed recurrent mutations in genes associated with cellular respiration, including cytochrome oxidase (cydA, cyoC) and ATP synthase (atpG). RT-qPCR analysis revealed an induction of gene expression associated with biofilm matrix production (especially curli synthesis), stress responses, active and passive transport and cell respiration during PHMB exposure, providing insight into potential physiological responses associated with adaptive crossresistance. In addition, confocal laser scanning microscopy (CLSM) observations demonstrated a global effect of PHMB on biofilm architectures and compositions formed by most E. coli strains, with the appearance of dense cellular clusters after a 24h-exposure. In conclusion, our results showed that the PHMB exposure stimulated the emergence of an adaptive cross-resistance to gentamicin in biofilms, likely induced through the activation of physiological responses and biofilm structural modulations altering gradients and microenvironmental conditions in the biological edifice.
... It has been well documented that bacteria resistant to aminoglycosides and carrying genes such as aac(6′)-Ib/Ibcr, rmtB, and armA are often resistant to multiple other antibiotics. (Ahmed et al., 2023;Bodendoerfer et al., 2020;Cirit et al., 2019) Therefore, implementing In the present study, it was observed that the majority of isolates carried only one PMQR gene. This is consistent with a previous report, which found that a single PMQR was present in 83.7% of Enterobacteriaceae isolates (Machuca et al., 2017). ...
The plasmid-mediated quinolone resistance (PMQR) and 16S ribosomal RNA (rRNA) methylase genes can lead to high-level bacterial resistance to various antibiotics, including quinolones and aminoglycosides. This study determined the prevalence of PMQR and 16S rRNA methylase determinants in clinical Escherichia coli. Non-duplicate E. coli resistant to quinolones (nalidixic acid, ciprofloxacin, or norfloxacin) and/or aminoglycosides (amikacin or gentamicin) were collected from patients at King Abdullah Hospital, Bisha, Saudi Arabia. A multiplex PCR was performed to identify the targeted genes. Out of 107 screened isolates, 44 (41%) were found to carry resistance genes, individually or in combination, including 41 PMQR and 14 16S rRNA methylase. The qnrS gene had the highest prevalence (23.4%) among PMQR, followed by aac(6′)-Ib (16.8%). Of the 14 identified 16S rRNA methylase, 8 were rmtB and 6 were armA. Out of 44 positive isolates, 72.7% carried only one resistance gene, 25% had co-existing resistance genes, with qnrS and rmtB or aac(6)-Ib and armA being the most common pairs. A single isolate was carried three genes (qnrS, aac(6′)-Ib and rmtB). As antibiotic resistance continues to become more prevalent, there is a need for extensive research to identify the genetic determinants of resistance and to develop new antibiotic therapies.
... In most situations, however, AG therapy may be discontinued after 48 to 72 h (the approximate time needed to obtain the results of the antibiogram). Clinicians must be aware of ESBL risk factors and coresistance to select appropriate antibiotics that may avoid the unnecessary use of aminoglycosides [20]. The two fundamental mechanisms of resistance to aminoglycosides in Enterobacterales are enzymatic modification or modification of their target [21,22]. ...
Aminoglycosides are a family of rapidly bactericidal antibiotics that often remain active against resistant Gram-negative bacterial infections. Over the past decade, their use in critically ill patients has been refined; however, due to their renal and cochleovestibular toxicity, their indications in the treatment of sepsis and septic shock have been gradually reduced. This article reviews the spectrum of activity, mode of action, and methods for optimizing the efficacy of aminoglycosides. We discuss the current indications for aminoglycosides, with an emphasis on multidrug-resistant Gram-negative bacteria, such as extended-spectrum β-lactamase-producing Enterobacterales, carbapenemase-producing Enterobacterales, multidrug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii. Additionally, we review the evidence for the use of nebulized aminoglycosides.
... These include fluoroquinolones, aminoglycosides, and fosfomycin as well as sulfonamides and trimethoprim [9]. Various resistance mechanisms also exist to impact the efficacy of these drugs and are often found in ESBL producing strains [26,47]. ...
Escherichia coli is a versatile commensal and pathogenic member of the human microflora. As the primary causative pathogen in urosepsis, E. coli places an immense burden on healthcare systems worldwide. To further exacerbate the issue, multi drug resistance (MDR) has spread rapidly through E. coli populations, making infections more troublesome and costlier to treat. This paper aimed to review the literature concerning the development of MDR in uropathogenic E. coli (UPEC) and explore the existing evidence of current and emerging treatment strategies. While some MDR strains maybe treated with β-lactam-β-lactamase inhibitor combinations as well as cephalosporins, cephamycin, temocillin and fosfomycin, current treatment strategies for many MDR UPEC strains are reliant on carbapenems. Carbapenem overreliance may contribute to the alarming dissemination of carbapenem-resistance amongst some UPEC communities, which has ushered in a new age of difficult to treat infections. Alternative treatment options for carbapenem resistant UPEC may include novel β-lactam-β-lactamase or carbapenemase inhibitor combinations, cefiderocol, polymyxins, tigecycline, aminoglycosides or fosfomycin. For metallo-β-lactamase producing strains (e.g., NDM, IMP-4), combinations of cefazidime-avibacam with aztreonam have been used. Additionally, the emergence of new antimicrobials brings new hope to the treatment of such infections. However, continued research is required to successfully bring these into the clinic for the treatment of MDR E. coli urosepsis.
... ESBL-producing E. coli has become an emerging public health problem due to the clinical failure of empirical treatment protocols. Although the resistance mechanisms of ESBL-producing E. coli may IRAN vary, it has been shown that the most common resistance mechanism of E. coli isolates against β-lactams is the production of β-lactamases (21,22). The proliferation of E. coli strains that produce a variety of ESBLs makes continuous monitoring necessary for appropriate antibiotic use and infection control. ...
Background and Objectives: Antibiotics-resistant Escherichia coli strains are considered one of the most important causes of human and animal infections worldwide. The aim of current study was to detect common resistance (carbapenems and quinolones) genes by PCR.
Materials and Methods: A total of 100 E. coli strains isolated from human urinary tract infection and 20 isolated strains of aborted sheep embryos were collected. PCR was performed using specific primers to detect the resistance genes.
Results: Overall, among the quinolones resistance genes, qnrS resistance gene had the highest frequency (48%) and among carbapenem resistance genes, imp resistance gene had the highest frequency (45%). The frequency of resistance genes, IMP (28.45%), KPC (9.5%), VIM (9.15%), NDM (7.20%) were observed in clinical and veterinary strains, respectively. According to the results, 38.6% of E. coli strains had at least one from five genes of resistance to quinolones. The lowest frequency of resistance gene was related to qnrA, which was observed in only 29 (24.2%) strains.
Conclusion: Monitoring of carbapenem and quinolone resistance in pathogenic E. coli to humans and animals has an important value in revising treatment guidelines and the national public health, and plays an important role in preventing the spread of resistant strains.
