Mobile fosfomycin resistance genes in Enterobacteriaceae—An increasing threat

Zurfluh, Katrin; Treier, Andrea; Schmitt, Kira; Stephan, Roger

doi:10.1002/mbo3.1135

Cited by 62 publications

(45 citation statements)

References 57 publications

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“…Presently, fosA3 is widely distributed among E. coli strains isolated from Asian countries, the United States, and Europe ( Wachino et al, 2010 ; Hou et al, 2012 ; Lee et al, 2012 ; Alrowais et al, 2015 ; Benzerara et al, 2017 ; Wang et al, 2017 ; Sorlozano-Puerto et al, 2020 ). Therefore, the possible global dissemination of fosA3 -bearing E. coli isolates has become a serious public health concern ( Zurfluh et al, 2020 ). Conjugative plasmids, particularly IncF and IncN plasmids seem to play a predominant role in the rapid dissemination of the fosA3 gene ( Yang et al, 2014 ; Villa et al, 2015 ; Huang et al, 2020 ; Zurfluh et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the possible global dissemination of fosA3 -bearing E. coli isolates has become a serious public health concern ( Zurfluh et al, 2020 ). Conjugative plasmids, particularly IncF and IncN plasmids seem to play a predominant role in the rapid dissemination of the fosA3 gene ( Yang et al, 2014 ; Villa et al, 2015 ; Huang et al, 2020 ; Zurfluh et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Occurrence and molecular epidemiology of fosA3-bearing Escherichia coli from ducks in Shandong province of China

et al. 2022

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The plasmid-borne fosfomycin resistance gene fosA3 has been identified in Escherichia coli ( E. coli ) from various animals but has rarely been reported in ducks. In this study, we investigated the fosA3 prevalence and molecular characteristics of fosA3 -harboring E. coli strains from ducks in Shandong province of China. In 416 E. coli isolates, 91 (21.88%) were identified as fosA3 -bearing strains, and the fosfomycin-resistant phenotype of 88 of the 91 fosA3 -harboring strains was successfully transferred to the recipient strains. Seven different genetic structures surrounding the fosA3 gene were detected and 2 new contexts were discovered among the fosA3 -carrying E. coli . Twenty fosA3 -harboring isolates and their trans-conjugants were randomly selected for pulsed-field gel electrophoresis ( PFGE ) typing and S1-nuclease PFGE, respectively. The PFGE patterns revealed that the 20 randomly selected fosA3 -bearing isolates were not a result of clonal dissemination. S1-PFGE showed that 15 of the 20 randomly selected trans-conjugants carried a single plasmid, and these 15 plasmids that harbored fosA3 (55–190 kb) were distributed into the following replicon types: IncF (n = 11), IncI1 (n = 1), IncN (n = 1), untypable (n = 1), and W-FIC (n = 1). Additionally, as vectors for fosA3 in E. coli , F-:A1:B6, N/ST1, IncI1/ST2, W-FIC, and one untypable plasmid had never been reported before. These observations highlighted the importance of ducks as a reservoir for multidrug-resistant fosA3 -carrying E. coli .

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Occurrence and molecular epidemiology of fosA3-bearing Escherichia coli from ducks in Shandong province of China

et al. 2022

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“…Tigecycline, colistin, Fosfomycin, and ceftazidime–avibactam were considered as the most effective agents for the CRKP infection treatments, and were even regarded as the last “trump card” to defend against CRKP ( Doi, 2019 ). However, clinical isolates resistant to those four antibiotics emerged frequently ( Petrosillo et al, 2019 ; Fang et al, 2020 ; Yahav et al, 2020 ; Zurfluh et al, 2020 ; Yusuf et al, 2021 ). Hence, verifying the related mechanism and demonstrating the potential of the spread of these resistant phenotypes in clinical isolate are urgent, which are the vital clues to solve antibiotic resistance.…”

Section: Introductionmentioning

confidence: 99%

The Co-occurrence of NDM-5, MCR-1, and FosA3-Encoding Plasmids Contributed to the Generation of Extensively Drug-Resistant Klebsiella pneumoniae

Zhou

Cao

et al. 2022

Front. Microbiol.

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The rise and global dissemination of extensively drug-resistant (XDR) bacteria are often related to plasmid-borne mobile antimicrobial resistance genes. Notably, isolates having multiple plasmids are often highly resistant to almost all the antibiotics available. In this study, we characterized an extensively drug-resistant Klebsiella pneumoniae 1678, which exhibited high-level resistance to almost all the available antibiotics. Through whole-genome sequencing (WGS), more than 20 resistant elements and 5 resistant plasmids were observed. Notably, the tigecycline resistance of K. pneumoniae 1678 was not related to the plasmid-borne tetA gene but associated with the overexpression of AcrAB and OqxAB efflux pumps, according to the susceptibility results of tetA-transformant and the related mRNA quantification of RND efflux pumps. Except for tigecycline resistance, three plasmids, mediating resistance to colistin, Fosfomycin, and ceftazidime–avibactam, respectively, were focused. Detailed comparative genetic analysis showed that all these plasmids belonged to dominated epidemic plasmids, and harbored completed conjugation systems. Results of conjugation assay indicated that these three plasmids not only could transfer to E. coli J53 with high conjugation frequencies, respectively, but also could co-transfer to E. coli J53 effectively, which was additionally confirmed by the S1-PFGE plasmids profile. Moreover, multiple insertion sequences (IS) and transposons (Tn) were also found surrounding the vital resistant genes, which may form several novel mechanisms involved in the resistant determinants’ mobilization. Overall, we characterized and reported the uncommon co-existence and co-transferring of FosA3-, NDM-5, and MCR-1-encoding plasmids in a K. pneumoniae isolate, which may increase the risk of spread of these resistant phenotypes and needing great concern.

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“…To date, 10 fosA variants ( fosA1 ∼ fosA10 ) have been identified in Enterobacteriaceae since the first fosA (namely fosA1 ) described in Serratia marcescens in 1980 ( Mendoza et al, 1980 ; Zurfluh et al, 2020 ). Fosfomycin resistance has been sporadically reported in Salmonella , one of the leading foodborne pathogens ( Lin and Chen, 2015 ; Qi et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Chromosomally Located fosA7 in Salmonella Isolates From China

Wang

et al. 2021

Front. Microbiol.

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This study aimed to investigate the prevalence of fosfomycin fosA7 in Salmonella enterica isolates from food animals and retail meat products in China and the impact of fosA7 on bacterial fitness. A total of 360 Salmonella isolates collected from 11 provinces and cities in China were detected for fosA7. All fosA7-positive Salmonella isolates were determined minimum inhibitory concentrations (MICs) and sequenced by Illumina Hiseq. The fosA7 gene of S. Derby isolate HA2-WA5 was knocked out. The full length of fosA7 was cloned into vector pBR322 and then transformed into various hosts. MICs of fosfomycin, growth curves, stability, and fitness of fosA7 were evaluated. The fosA7 gene was identified in S. Derby (ST40, n = 30) and S. Reading (ST1628, n = 5). MICs to fosfomycin of 35 fosA7-positive isolates were 1 to 32 mg/L. All fosA7 were located on chromosomes of Salmonella. The deletion of fosA7 in HA2-WA5 decreased fosfomycin MIC by 16-fold and slightly affected its fitness. The acquisition of plasmid-borne fosA7 enhanced MICs of fosfomycin in Salmonella (1,024-fold) and Escherichia coli (16-fold). The recombinant plasmid pBR322-fosA7 was stable in Salmonella Typhimurium, S. Pullorum, S. Derby, and E. coli, except for Salmonella Enteritidis, and barely affected on the growth of them but significantly increased biological fitness in Salmonella. The spread of specific Salmonella serovars such as S. Derby ST40 will facilitate the dissemination of fosA7. fosA7 can confer high-level fosfomycin resistance and enhance bacterial fitness in Salmonella if transferred on plasmids; thus, it has the potential to be a reservoir of the mobilized fosfomycin resistance gene.

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Mobile fosfomycin resistance genes in Enterobacteriaceae—An increasing threat

Cited by 62 publications

References 57 publications

Occurrence and molecular epidemiology of fosA3-bearing Escherichia coli from ducks in Shandong province of China

Occurrence and molecular epidemiology of fosA3-bearing Escherichia coli from ducks in Shandong province of China

The Co-occurrence of NDM-5, MCR-1, and FosA3-Encoding Plasmids Contributed to the Generation of Extensively Drug-Resistant Klebsiella pneumoniae

Chromosomally Located fosA7 in Salmonella Isolates From China

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