Skip to main content
NCBI home page
Wiley Open Access Collection logoLink to Wiley Open Access Collection
. 2021 May 6;68(6):3048–3054. doi: 10.1111/tbed.13980

Colistin‐resistant Entero bacter kobei carrying mcr‐9.1 and bla CTX‐M‐15 infecting a critically endangered franciscana dolphin (Pontoporia blainvillei), Brazil

Danny Fuentes‐Castillo 1,2, Fábio P Sellera 2,3, Daphne W Goldberg 4, Herrison Fontana 2,5, Fernanda Esposito 2,5, Brenda Cardoso 2,6, Joana Ikeda 7, Anneliese Kyllar 7,8, José L Catão‐Dias 1, Nilton Lincopan 2,5,6,✉
PMCID: PMC9290994  PMID: 33411986

Abstract

The emergence of mobile mcr genes mediating resistance to colistin is a critical public health issue that has hindered the treatment of serious infections caused by multidrug‐resistant pathogens in humans and other animals. We report the emergence of the mcr‐9.1 gene in a polymyxin‐resistant extended‐spectrum β‐lactamase (ESBL)‐producing Enterobacter kobei infecting a free‐living franciscana dolphin (Pontoporia blainvillei), threatened with extinction in South America. Genomic analysis confirmed the presence of genes conferring resistance to clinically relevant β‐lactam [bla CTX‐M‐15, bla ACT‐9, bla OXA‐1 and bla TEM‐1B], aminoglycoside [aac(3)‐IIa, aadA1, aph(3'')‐Ib and aph(6)‐Id], trimethoprim [dfrA14], tetracycline [tetA], quinolone [aac(6')‐Ib‐cr and qnrB1], fosfomycin [fosA], sulphonamide [sul2] and phenicol [catA1 and catB3] antibiotics. The identification of mcr‐9.1 in a CTX‐M‐15‐producing pathogen infecting a critically endangered animal is of serious concern, which should be interpreted as a sign of further spread of critical priority pathogens and their resistance genes in threatened ecosystems.

Keywords: Enterobacterales, MCR, multidrug‐resistant, One Health, polymyxin, Wildlife

1. INTRODUCTION

The global emergence and rapid dissemination of mobile phosphoethanolamine transferase mcr genes, responsible for transferable colistin resistance in Enterobacterales, is a public health concern (El‐Sayed Ahmed et al., 2020; Wang, Liu, et al., 2020). In this regard, since the first report of the mcr‐1 gene, in 2015, novel alleles including mcr‐2, mcr‐3, mcr‐4, mcr‐5, mcr‐6, mcr‐7, mcr‐8, mcr‐9 and mcr‐10 have been globally identified (El‐Sayed Ahmed et al., 2020; Li et al., 2020; Ling et al., 2020; Liu et al., 2016; Wang, Feng, et al., 2020). Worryingly, the occurrence of mcr genes has been documented in critical priority extended‐spectrum β‐lactamase (ESBL)‐producing pathogens, mostly isolated from humans and food‐producing animals (El‐Sayed Ahmed et al., 2020; Liu et al., 2016; Wang, Liu, et al., 2020).

The franciscana dolphin (Pontoporia blainvillei) is considered the most threatened small cetacean in the south‐western Atlantic Ocean, which includes the coasts of Brazil, Uruguay and Argentina (Sucunza et al., 2018). Due to their coastal habits, these animals have been frequently exposed to different degrees of anthropogenic impacts, including fisheries by catch and habitat degradation (Sucunza et al., 2018). Consequently, this species is currently listed as vulnerable to extinction by the International Union for Conservation of Nature (Cunha et al., 2014; Zerbini et al., 2017), and as critically endangered by the Red Book of Threatened Species of Fauna, Brazil (ICMBio, 2018).

In this study, we report the emergence of mcr‐9.1 in an ESBL‐producing E. kobei infecting a free‐living franciscana dolphin in Brazil. Additionally, an epidemiological landscape of global distribution of MCR‐9‐producing Enterobacterales circulating at human‐animal interface is presented.

2. MATERIALS AND METHODS

In December 2019, a female neonate franciscana was found stranded alive in Mambucaba Beach, in Angra dos Reis (−23.027184, −44.518130), located in the Southern coast of Rio de Janeiro state, Brazil (Figure S1). The animal was rescued by the staff of the Santos Basin Beach Monitoring Project (PMP‐BS), presenting excoriations on the head and with part of the umbilical cord still present. The dolphin was closely monitored, receiving intensive care and bottle‐feeding with a special dolphin formula every 3 hr. However, after 11 hr in captivity, the animal began to exhibit clinical signs of shock leading to death. In order to determine the main causes of death, necropsy was performed, where histopathological analysis of fixed lung tissue revealed severe pneumonia. Additionally, bacteriological culture of respiratory exudate collected through the spiracle was positive for Gram‐negative bacilli.

Antimicrobial susceptibility testing was performed by the disc diffusion method (CLSI, 2020), including amoxicillin/clavulanic acid, aztreonam, cefotaxime, ceftriaxone, cefepime, cefoxitin, ceftiofur, ciprofloxacin, enrofloxacin, chloramphenicol, amikacin, gentamicin, ertapenem, imipenem, meropenem, sulfamethoxazole/trimethoprim and tetracycline. In addition, colistin susceptibility testing was performed by broth microdilution method (EUCAST, 2020). The minimum inhibitory concentration (MIC) for fosfomycin was determined by using the agar dilution method (CLSI, 2020). ESBL production was screened by the double‐disc synergy test (DDST; Jarlier et al., 1988). Escherichia coli ATCC 25,922 was used as control strain. Bacterial conjugation for the mcr‐9.1‐positive E. kobei isolate was done in a liquid and solid mating‐out assay (Lampkowska et al., 2008), using the azide‐resistant E. coli C600 as recipient.

Genomic DNA was extracted and used to construct a paired‐end library, which was sequenced using the NextSeq 550 platform (Illumina), using paired‐end reads (150 bp). De novo genome assembly and contig annotation was carried out using CLC Genomics Workbench 12.0.3. Prediction of bacterial species, resistome and plasmidome was performed using fast K‐mer algorithm KmerFinder 3.2 (Larsen et al., 2014), ResFinder 3.2 (Zankari et al., 2012) and PlasmidFinder 2.1 (Carattoli et al., 2014) databases, respectively (http://www.genomicepidemiology.org/).

3. RESULTS AND DISCUSSION

The Gram‐negative bacilli were identified as belonging to the Enterobacter cloacae complex (E11R strain) by using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF). The E11R strain displayed a multidrug‐resistant (MDR) profile (Magiorakos et al., 2012) to amoxicillin/clavulanic acid, aztreonam, cefotaxime, ceftriaxone, cefepime, cefoxitin, ceftiofur, ciprofloxacin, enrofloxacin, chloramphenicol, fosfomycin (MIC, >1,024 µg/ml), gentamicin, sulfamethoxazole/trimethoprim and tetracycline, remaining susceptible to ertapenem, imipenem, meropenem and amikacin. Furthermore, E11R strain exhibited resistance to colistin (MIC, 16 µg/ml), whereas ESBL production was detected by the DDST.

Genomic analysis identified the E11R strain as E. kobei, confirming a wide resistome, with genes conferring resistance to colistin [mcr‐9.1], β‐lactams [bla CTX‐M‐15, bla ACT‐9, bla OXA‐1 and bla TEM‐1B], aminoglycosides [aac(3)‐IIa, aadA1, aph(3'')‐Ib and aph(6)‐Id], trimethoprim [dfrA14], tetracycline [tetA], quinolones [aac(6')‐Ib‐cr and qnrB1], fosfomycin [fosA], sulphonamide [sul2] and phenicols [catA1 and catB3]. IncHI2 and IncHI2A replicons were detected, and analysis of the genetic environment confirmed that mcr‐9.1 was flanked by the insertion sequences IS903B and IS26, as previously reported (Figure 1; Kieffer et al., 2019; Lin et al., 2020; Tyson et al., 2020; Yuan et al., 2019). The region upstream of mcr‐9.1 in E. kobei E11R strain included nucleotidyltransferase (NTase, transferase enzyme), IS26, pcoS (encoding a two‐component sensor histidine kinase) and IS903B. On the other hand, the region downstream of mcr‐9.1 included wbuC (encoding a cupin fold metalloprotein), but no genes encoding the two‐component system qseC‐qseB, which has been associated with the expression of mcr‐9 in other Enterobacterales (Kananizadeh et al., 2020; Kieffer et al., 2019). Conjugation attempts to evaluate the transferability of the mcr‐9.1 gene were unsuccessful. In this regard, absence of the qseC‐qseB genes in the E. kobei E11R strain could be associated with the unsuccessful selection of transconjugants in agar plates supplemented with colistin (1 mg/ml) (Tyson et al., 2020).

FIGURE 1.

FIGURE 1

Open in a new tab

Genetic context of the mcr‐9.1 gene in the colistin‐resistant Enterobacter kobei strain E11R. IS903B and IS26 elements were found upstream and downstream of mcr‐9.1 in a similar way that in MCR‐9‐producing Enterobacter spp. DKU_NT_01 strain (GenBank accession number: CP021137.1) isolated from soybean in South Korea; Salmonella Saintpaul [CVM N16S133 (CP049986.1), NY‐N14748 (CP048926.1), CVM N40391 (CP049983.1) and CVM N52030 (CP049981.1)], S. Heidelberg [CVM N16S321 (CP049313.1), CVM N58631 (CP049307.1) and CVMN53023 (CP049310.1)], and S. Albany [CVM N18S2238 (CP049312)] strains isolated from ground turkey; S. Johannesburg [CVM N58011 (CP049309)] strain isolated from chicken breast; and Escherichia coli [CVM N18EC0432 (CP048293.1)] strain isolated from chicken wings, in the United States of America (Tyson et al., 2020)

In recent years, colistin has been used as a last‐resort for the treatment of infections caused by multidrug‐resistant and/or carbapenem‐resistant Gram‐negative bacteria (El‐Sayed Ahmed et al., 2020). However, the previous and extensive use of colistin in production animals, as a growth promoter or for prophylaxis, has been recognized as a responsible factor for the emergence and the rapid dissemination of mobile colistin resistance (mcr) genes (Rhouma et al., 2016). In this respect, since the detection of mcr‐1, nine additional mcr homologues have been described, with several gene variants occurring worldwide (El‐Sayed Ahmed et al., 2020; Wang, Liu, et al., 2020).

The mcr‐9.1 allele was identified for the first time in Salmonella Typhimurium isolated from a human patient (Carroll et al., 2019) and currently has been reported worldwide with a rapid dissemination among Enterobacterales from human, food, poultry, pets, swine and horse samples (Figure 2). Recently, two novel variants, mcr‐9.2 and mcr‐9.3, have been identified in Enterobacter hormaechei subsp. xiangfangensis (GenBank accession number: MN164032.1) and Klebsiella pneumoniae (GenBank accession number: MT505326.1) isolates, respectively.

FIGURE 2.

FIGURE 2

Open in a new tab

Global distribution of MCR‐9‐positive Enterobacterales. The occurrence of MCR‐9‐producing Enterobacterales (i.e. Citrobacter freundii, Citrobacter telavivum, Enterobacter asburiae, Enterobacter cloacae, Enterobacter hormaechei, Enterobacter kobei, Enterobacter xiangfangensis Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella quasipneumoniae, Klebsiella variicola, Providencia alcalifaciens and Salmonella enterica) has been reported in Argentina (1, Faccone et al., 2020), Australia (2, Kamathewatta et al., 2020), Belgium (3, Wang, Liu, et al., 2020), Brazil (4, Saidenberg et al., 2020; 5, Leite et al., 2020; 6, This study), Colombia (7, Rada et al., 2020), China (8, Yuan et al., 2019; 9, Lin et al., 2020; 10, Pan et al., 2020), Denmark (3, Wang, Liu, et al., 2020), Egypt (11, Khalifa, Oreiby, 2020; 12, Sadek et al., 2020; 13, Soliman et al., 2020), France (14, Kieffer et al., 2019), Germany (15, Borowiak et al., 2020), Israel (16, Ribeiro et al., 2020), Japan (17, Kananizadeh et al., 2020; 18, Khalifa, Soliman, et al., 2020), Korea (19, Cha et al., 2020), Montenegro (3, Wang, Liu, et al., 2020), Poland (3, Wang, Liu, et al., 2020), Qatar (20, Tsui et al., 2020), Romania (3, Wang, Liu, et al., 2020), Serbia (3, Wang, Liu, et al., 2020), Slovenia (3, Wang, Liu, et al., 2020), South Africa (21, Sekyere et al., 2020), Spain (3, Wang, Liu, et al., 2020), Sweden (22, Börjesson et al., 2020) and the United States of America (23, Carrol et al, 2019; 24, Chavda et al., 2019; 25, Tyson et al., 2020), from human and non‐human sources

In this study, we report the emergence of mcr‐9.1 in an ESBL‐producing E. kobei isolated from an infected free‐living franciscana dolphin, a species critically endangered by anthropogenic activities in Brazil (Cunha et al., 2014; ICMBio, 2018). The occurrence of CTX‐M‐15‐producing E. coli has been reported in captive dolphins (Manageiro et al., 2015), and now, we demonstrated that this type of pathogen can also threaten free‐living dolphins, which may have serious implications for wild populations and associated ecosystems.

The environmental dissemination of critical priority pathogens has been considered a serious threat to ecosystem maintenance (de Carvalho et al., 2020; Sevilla et al., 2020; Founou et al., 2019; Sekyere et al., 2020). This issue considered another form of environmental pollution (Guenther et al., 2011), could also substantially increase the risk for marine populations acquire such bacteria (Power et al., 2016). Specifically in Brazilian coast, the occurrence of MCR‐type, ESBL‐ and/or carbapenemase‐producing bacteria has been documented in recreational waters (Campana et al., 2017; Fernandes et al., 2017; Paschoal et al., 2017; Sellera, Fernandes, Moura, et al., 2017), beach sand samples (Furlan et al., 2020), mangrove waters (Sacramento et al., 2018), and marine hosts (Goldberg et al., 2019; Sellera et al., 2018; Sellera, Fernandes, Sartori, et al., 2017). In this way, considering the One Health perspective, environment and wild animals are also acting as bioindicators for clinically important antibiotic‐resistant pathogens that can seriously affect human communities related with these ecosystems (McEwen & Collignon, 2018; White & Hughes, 2019).

In summary, we report the emergence of MCR‐9‐producing bacteria in marine wildlife. Considering that oceanic environments and human and animal health are strictly connected, the dissemination of clinically important MDR pathogens in marine ecosystems must be viewed as serious One Health problem. Finally, since multidrug‐resistant pathogens have begun to be associated with fatal cases of infections in endangered animals (Fuentes‐Castillo et al., 2020), continued surveillance of MCR‐ and ESBL‐producing bacteria in marine ecosystems should be globally performed for a better comprehension of the transmission pathways and clinical impacts on marine wildlife.

CONFLICT OF INTERESTS

No potential conflict of interest was reported by the authors.

ETHICAL APPROVAL

The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to. No ethical approval was required for this specific study. The licences and research permit for monitoring programme and the biological sampling were issued by the Brazilian government (IBAMA‐ABIO 624/2015); all animal handling procedures and protocols followed the required ethics and welfare practices.

Supporting information

Supplementary Material

Click here for additional data file. (626.5KB, docx)

ACKNOWLEDGEMENTS

This work was supported by Bill & Melinda Gates Foundation, Grand Challenges Explorations Brazil—New approaches to characterize the global burden of antimicrobial resistance [grant OPP1193112]; Fundação de Amparo à Pesquisa do Estado de São Paulo [FAPESP 19/15578‐4]; Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq 443819/2018‐1, 312249/2017‐9 and 433128/2018‐6]; Comisión Nacional de Investigación Científica y Tecnológica [CONICYT BCH 72170436]; and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior [CAPES 88882.333054/2019‐01, 88887.506496/2020‐00]. N. L. and J.L C‐D are research fellows of CNPq (312249/2017‐9 and 304999/2018‐0). We thank Cefar Diagnóstica Ltda. (São Paulo, Brazil) and CEFAP‐GENIAL facility for kindly supplying antibiotic discs for susceptibility testing and Illumina sequencing, respectively. We gratefully acknowledge Petrobras for the permission to use these data. The Santos Basin Beach Monitoring Project (Projeto de Monitoramento de Praias da Bacia de Santos—PMP‐BS), conducted from Laguna/SC to Saquarema/RJ, is a requirement set by the Brazilian Institute of the Environment (IBAMA) for the environmental licensing of the oil and natural gas production and transport by Petrobras.

Fuentes‐Castillo D, Sellera FP, Goldberg DW, et al. Colistin‐resistant Entero bacter kobei carrying mcr‐9.1 and bla CTX‐M‐15 infecting a critically endangered franciscana dolphin (Pontoporia blainvillei), Brazil. Transbound Emerg Dis. 2021;68:3048–3054. 10.1111/tbed.13980

[The copyright line for this article was changed on 11 May 2021 after first online publication].

DATA AVAILABILITY STATEMENT

The whole genome nucleotide sequence of the E. kobei E11R isolate is available in the GenBank database under accession number PRJNA615090. Additionally, genomic data of E. kobe E11R strain will be available in the OneBR platform (http://onehealthbr.com/) under the accession number OneBR‐ER1.

REFERENCES

  1. Börjesson, S. , Greko, C. , Myrenås, M. , Landén, A. , Nilsson, O. , & Pedersen, K. (2020). A link between the newly described colistin resistance gene mcr‐9 and clinical Enterobacteriaceae isolates carrying bla SHV‐12 from horses in Sweden. Journal of Global Antimicrobial Resistance, 20, 285–289. 10.1016/j.jgar.2019.08.007 [DOI] [PubMed] [Google Scholar]
  2. Borowiak, M. , Baumann, B. , Fischer, J. , Thomas, K. , Deneke, C. , Hammerl, J. A. , Szabo, I. , & Malorny, B. (2020). Development of a novel mcr‐6 to mcr‐9 multiplex PCR and assessment of mcr‐1 to mcr‐9 occurrence in colistin‐resistant Salmonella enterica isolates from environment, feed, animals and food (2011–2018) in Germany. Frontiers in Microbiology, 11, 80. doi: 10.3389/fmicb.2020.00080 [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campana, E. H. , Montezzi, L. F. , Paschoal, R. P. , & Picão, R. C. (2017). NDM‐producing Klebsiella pneumoniae ST11 goes to the beach. International Journal of Antimicrobial Agents, 49(1), 119–121. 10.1016/j.ijantimicag.2016.10.006 [DOI] [PubMed] [Google Scholar]
  4. Carattoli, A. , Zankari, E. , García‐Fernández, A. , Voldby Larsen, M. , Lund, O. , Villa, L. , Møller Aarestrup, F. , & Hasman, H. (2014). In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrobial Agents and Chemotherapy, 58, 3895–3903. 10.1128/AAC.02412-14 [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carroll, L. M. , Gaballa, A. , Guldimann, C. , Sullivan, G. , Henderson, L. O. , & Wiedmann, M. (2019). Identification of novel mobilized colistin resistance gene mcr‐9 in a multidrug‐resistant, colistin‐susceptible Salmonella enterica serotype Typhimurium isolate. Mbio, 10(3), e00853–e919. 10.1128/mBio.00853-19 [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cha, M. H. , Woo, G. J. , Lee, W. , Kim, S. H. , Woo, J. H. , Kim, J. , Ryu, J. G. , Kwak, H. S. , & Chi, Y. M. (2020). Emergence of transferable mcr‐9 gene‐carrying colistin‐resistant Salmonella enterica Dessau ST14 isolated from retail chicken meat in Korea. Foodborne Pathogens and Disease, 17(11), 720–727. 10.1089/fpd.2020.2810 [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chavda, K. D. , Westblade, L. F. , Satlin, M. J. , Hemmert, A. C. , Castanheira, M. , Jenkins, S. G. , Chen, L. , & Kreiswirth, B. N. (2019). First report of blaVIM‐4‐ and mcr‐9‐coharboring Enterobacter Species isolated from a pediatric patient. mSphere, 4(5), e00629–e719. 10.1128/mSphere.00629-19 [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clinical and Laboratory Standards Institute . (2020). Performance standards for antimicrobial susceptibility testing: Fifteenth informational supplement M100–S30. CLSI. [Google Scholar]
  9. Cunha, H. A. , Medeiros, B. V. , Barbosa, L. A. , Cremer, M. J. , Marigo, J. , Lailson‐Brito, J. , Azevedo, A. F. , & Solé‐Cava, A. M. (2014). Population structure of the endangered franciscana dolphin (Pontoporia blainvillei): Reassessing management units. PLoS One, 9(1), e85633. 10.1371/journal.pone.0085633 [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. de Carvalho, M. , Fernandes, M. R. , Sellera, F. P. , Lopes, R. , Monte, D. F. , Hippólito, A. G. , Milanelo, L. , Raso, T. F. , & Lincopan, N. (2020). International clones of extended‐spectrum β‐lactamase (CTX‐M)‐producing Escherichia coli in peri‐urban wild animals, Brazil. Transboundary and Emerging Diseases, 67(5),1804–1815.doi: 10.1111/tbed.13558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. El‐Sayed Ahmed, M. , Zhong, L. L. , Shen, C. , Yang, Y. , Doi, Y. , & Tian, G. B. (2020). Colistin and its role in the Era of antibiotic resistance: An extended review (2000–2019). Emerging Microbes and Infections, 9(1), 868–885. 10.1080/22221751.2020.1754133 [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. European Committee on Antimicrobial Susceptibility Testing (EUCAST) . (2020). The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version10.0. Retrieved from https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_10.0_Breakpoint_Tables.pdf.
  13. Faccone, D. , Martino, F. , Albornoz, E. , Gomez, S. , Corso, A. , & Petroni, A. (2020). Plasmid carrying mcr‐9 from an extensively drug‐resistant NDM‐1‐producing Klebsiella quasipneumoniae subsp. quasipneumoniae clinical isolate. Infection, Genetics and Evolution, 81, 104273. 10.1016/j.meegid.2020.104273 [DOI] [PubMed] [Google Scholar]
  14. Fernandes, M. R. , Sellera, F. P. , Esposito, F. , Sabino, C. P. , Cerdeira, L. , & Lincopan, N. (2017). Colistin‐resistant mcr‐1‐positive Escherichia coli on public beaches, an infectious threat emerging in recreational waters. Antimicrobial Agents and Chemotherapy, 61(7), e00234–e317. 10.1128/AAC.00234-17 [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Founou, L. L. , Founou, R. C. , Ntshobeni, N. , Govinden, U. , Bester, L. A. , Chenia, H. Y. , Djoko, C. F. , & Essack, S. Y. (2019). Emergence and spread of extended spectrum β‐lactamase producing Enterobacteriaceae (ESBL‐PE) in pigs and exposed workers: a Multicentre Comparative Study between Cameroon and South Africa. Pathogens, 8(1), 10. 10.3390/pathogens8010010 [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fuentes‐Castillo, D. , Navas‐Suárez, P. E. , Gondim, M. F. , Esposito, F. , Sacristán, C. , Fontana, H. , Fuga, B. , Piovani, C. , Kooij, R. , Lincopan, N. , & Catão‐Dias, J. L. (2020). Genomic characterization of multidrug‐resistant ESBL‐producing Escherichia coli ST58 causing fatal colibacillosis in critically endangered Brazilian merganser (Mergus octosetaceus). Transboundary and Emerging Diseases, 10.1111/tbed.13686 [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Furlan, J. P. R. , dos Santos, L. D. R. , Ramos, M. S. , Gallo, I. F. L. , & Stehling, E. G. (2020). Presence of colistin resistance mcr‐4 gene and clinically relevant antimicrobial resistance genes in sand samples from a public beach. Water, Air, & Soil Pollution, 231, 321. 10.1007/s11270-020-04707-7 [DOI] [Google Scholar]
  18. Goldberg, D. W. , Fernandes, M. R. , Sellera, F. P. , Costa, D. , Loureiro Bracarense, A. P. , & Lincopan, N. (2019). Genetic background of CTX‐M‐15‐producing Enterobacter hormaechei ST114 and Citrobacter freundii ST265 co‐infecting a free‐living green turtle (Chelonia mydas). Zoonoses and Public Health, 66(5), 540–545. 10.1111/zph.12572 [DOI] [PubMed] [Google Scholar]
  19. Guenther, S. , Ewers, C. , & Wieler, L. H. (2011). extended‐spectrum beta‐lactamases producing E. coli in wildlife, yet another form of environmental pollution? Frontiers in Microbiology, 2(246), 1–13. 10.3389/fmicb.2011.00246 [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Instituto Chico Mendes de Conservação da Biodiversidade (ICMBIO) , (2018). Livro Vermelho da Fauna Brasileira Ameaçada de Extinção, (Vol. 1, pp. 1–492). Brasília: ICMBIO. Retrieved from https://www.icmbio.gov.br/portal/images/stories/comunicacao/publicacoes/publicacoes‐diversas/livro_vermelho_2018_vol1.pdf [Google Scholar]
  21. Jarlier, V. , Nicolas, M. H. , Fournier, G. , & Philippon, A. (1988). Extended broad‐spectrum beta‐lactamases conferring transferable resistance to newer beta‐lactam agents in Enterobacteriaceae: Hospital prevalence and susceptibility patterns. Reviews of Infectious Diseases, 10, 867–878. 10.1093/clinids/10.4.867 [DOI] [PubMed] [Google Scholar]
  22. Kamathewatta, K. , Bushell, R. , Rafa, F. , Browning, G. , Billman‐Jacobe, H. , & Marenda, M. (2020). Colonization of a hand washing sink in a veterinary hospital by an Enterobacter hormaechei strain carrying multiple resistances to high importance antimicrobials. Antimicrobial Resistance and Infection Control, 9(1), 163. 10.1186/s13756-020-00828-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kananizadeh, P. , Oshiro, S. , Watanabe, S. , Iwata, S. , Kuwahara‐Arai, K. , Shimojima, M. , Ogawa, M. , Tada, T. , & Kirikae, T. (2020). Emergence of carbapenem‐resistant and colistin‐susceptible Enterobacter cloacae complex co‐harboring blaIMP‐1 and mcr‐9 in Japan. BMC Infectious Diseases, 20(1), 282. 10.1186/s12879-020-05021-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Khalifa Hazim O., Oreiby Atef F., Abd El‐Hafeez Amer Ali, Okanda Takashi, Haque Anwaral, Anwar Kazi S., Tanaka Masaki, Miyako Keisuke, Tsuji Shoji, Kato Yasuyuki, Matsumoto Tetsuya (2020). First Report of Multidrug‐Resistant Carbapenemase‐Producing Bacteria Coharboring mcr‐9 Associated with Respiratory Disease Complex in Pets: Potential of Animal‐Human Transmission. Antimicrobial Agents and Chemotherapy, 65(1), e01890–20. 10.1128/aac.01890-20 [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Khalifa, H. O. , Soliman, A. M. , Saito, T. , Kayama, S. , Yu, L. , Hisatsune, J. , Sugai, M. , Nariya, H. , Ahmed, A. M. , Shimamoto, T. , Matsumoto, T. & Shimamoto, T. (2020). First report of bla VIM‐1‐, bla NDM‐1‐, and mcr‐9‐co‐harboring foodborne Klebsiella pneumoniae . Antimicrobial Agents and Chemotherapy, 64(9), e00882–e920. 10.1128/AAC.00882-20 [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kieffer, N. , Royer, G. , Decousser, J. W. , Bourrel, A. S. , Palmieri, M. , Ortiz De La Rosa, J. M. , Jacquier, H. , Denamur, E. , Nordmann, P. & Poirel, L. (2019). mcr‐9, an inducible gene encoding an acquired phosphoethanolamine transferase in Escherichia coli, and its origin. Antimicrobial Agents and Chemotherapy, 63(9), e00965–e1019. 10.1128/AAC.00965-19 [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lampkowska, J. , Feld, L. , Monaghan, A. , Toomey, N. , Schjorring, S. , Jacobsen, B. , Vandervoet, H. , Andersen, S. , Bolton, D. , Krogfelt, K. A. , Wilcks, A. , Bardowski, J. & Aarts, H. (2008). A standardized conjugation protocol to asses antibiotic resistance transfer between lactococcal species. International Journal of Food Microbiology, 127(1–2), 172–175. 10.1016/j.ijfoodmicro.2008.06.017 [DOI] [PubMed] [Google Scholar]
  28. Larsen, M. V. , Cosentino, S. , Lukjancenko, O. , Saputra, D. , Rasmussen, S. , Hasman, H. , Sicheritz‐Ponten, T. , Aarestrup, F. M. , Ussery, D. W. , & Lund, O. (2014). Benchmarking of methods for genomic taxonomy. Journal of Clinical Microbiology, 52(5), 1529–1539. 10.1128/JCM.02981-13 [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Leite, E. L. , Araújo, W. J. , Vieira, T. R. , Zenato, K. S. , Vasconcelos, P. C. , Cibulski, S. , Givisiez, P. E. N. , Cardoso, M. R. I. , & Oliveira, C. (2020). First genome of a mcr‐9‐mediated colistin‐resistant Salmonella Typhimurium from Brazilian livestock. Journal of Global Antimicrobial Resistance, S2213–7165(20), 30243–30245.Advance online publication. doi: 10.1016/j.jgar.2020.09.012. [DOI] [PubMed] [Google Scholar]
  30. Li, Y. , Dai, X. , Zeng, J. , Gao, Y. , Zhang, Z. , & Zhang, L. (2020). Characterization of the global distribution and diversified plasmid reservoirs of the colistin resistance gene mcr‐9 . Scientific Reports, 10(1), 8113. 10.1038/s41598-020-65106-w [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lin, M. , Yang, Y. , Yang, Y. , Chen, G. , He, R. , Wu, Y. , Zhong, L. L. , El‐Sayed Ahmed, M. A. E. , Feng, S. , Shen, C. , Wen, X. , Huang, J. , Li, H. , Zheng, X. & Tian, G. B. (2020). Co‐occurrence of mcr‐9 and bla NDM‐1 in Enterobacter cloacae isolated from a patient with bloodstream infection. Infection and Drug Resistance, 13, 1397–1402. 10.2147/IDR.S248342 [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ling, Z. , Yin, W. , Shen, Z. , Wang, Y. , Shen, J. , & Walsh, T. R. (2020). Epidemiology of mobile colistin resistance genes mcr‐1 to mcr‐9 . Journal of Antimicrobial Chemotherapy, in Press, 2020, 10.1093/jac/dkaa205 [DOI] [PubMed] [Google Scholar]
  33. Liu, Y.‐Y. , Wang, Y. , Walsh, T. R. , Yi, L.‐X. , Zhang, R. , Spencer, J. , Doi, Y. , Tian, G. , Dong, B. , Huang, X. , Yu, L.‐F. , Gu, D. , Ren, H. , Chen, X. , Lv, L. , He, D. , Zhou, H. , Liang, Z. , Liu, J.‐H. , & Shen, J. (2016). Emergence of plasmid‐mediated colistin resistance mechanism MCR‐1 in animals and human beings in China: A microbiological and molecular biological study. Lancet Infectious Diseases, 16(2), 161–168. 10.1016/S1473-3099(15)00424-7 [DOI] [PubMed] [Google Scholar]
  34. Magiorakos, A.‐P. , Srinivasan, A. , Carey, R. B. , Carmeli, Y. , Falagas, M. E. , Giske, C. G. , Harbarth, S. , Hindler, J. F. , Kahlmeter, G. , Olsson‐Liljequist, B. , Paterson, D. L. , Rice, L. B. , Stelling, J. , Struelens, M. J. , Vatopoulos, A. , Weber, J. T. , & Monnet, D. L. (2012). Multidrug‐resistant, extensively drug‐resistant and pandrug‐resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clinical Microbiology and Infection, 18(3), 268–281. 10.1111/j.1469-0691.2011.03570.x [DOI] [PubMed] [Google Scholar]
  35. Manageiro, V. , Clemente, L. , Jones‐Dias, D. , Albuquerque, T. , Ferreira, E. , & Caniça, M. (2015). CTX‐M‐15‐producing Escherichia coli in dolphin. Portugal. Emerging Infectious Diseases, 21(12), 2249–2251. 10.3201/eid2112.141963 [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. McEwen, S. A. , & Collignon, P. J. (2018). Antimicrobial resistance: A one health perspective. Microbiology Spectrum, 6(2), 10.1128/microbiolspec.ARBA-0009-2017 [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Pan, Y. , Fang, Y. , Song, X. , Lyu, N. , Chen, L. , Feng, Y. , & Hu, Y. (2020). Co‐occurrence of mcr‐9, extended spectrum β‐lactamase (ESBL) and AmpC genes in a conjugative IncHI2A plasmid from a multidrug‐resistant clinical isolate of Salmonella diarizonae . The Journal of Infection, S0163–4453(20), 30703–30709.Advance online publication. doi: 10.1016/j.jinf.2020.11.008. [DOI] [PubMed] [Google Scholar]
  38. Paschoal, R. P. , Campana, E. H. , Corrêa, L. L. , Montezzi, L. F. , Barrueto, L. R. L. , da Silva, I. R. , Bonelli, R. R. , Castro, L. D. S. , & Picão, R. C. (2017). Concentration and variety of carbapenemase producers in recreational coastal waters showing distinct levels of pollution. Antimicrobial Agents and Chemotherapy, 61(12), e01963–e2017. 10.1128/AAC.01963-17 [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Power, M. L. , Samuel, A. , Smith, J. J. , Stark, J. S. , Gillings, M. R. , & Gordon, D. M. (2016). Escherichia coli out in the cold: Dissemination of human‐derived bacteria into the Antarctic microbiome. Environmental Pollution, 215, 58–65. 10.1016/j.envpol.2016.04.013 [DOI] [PubMed] [Google Scholar]
  40. Rada Ana M., De La Cadena Elsa, Agudelo Carlos, Capataz Cesar, Orozco Nataly, Pallares Cristian, Dinh An Q., Panesso Diana, Ríos Rafael, Diaz Lorena, Correa Adriana, Hanson Blake M., Villegas Maria V., Arias Cesar A., Restrepo Eliana (2020). Dynamics of blaKPC‐2 Dissemination from Non‐CG258 Klebsiella pneumoniae to Other Enterobacterales via IncN Plasmids in an Area of High Endemicity. Antimicrobial Agents and Chemotherapy, 64(12), 1–9. 10.1128/aac.01743-20 [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rhouma, M. , Beaudry, F. , & Letellier, A. (2016). Resistance to colistin: what is the fate for this antibiotic in pig production? International Journal of Antimicrobial Agents, 48(2), 119–126. 10.1016/j.ijantimicag.2016.04.008 [DOI] [PubMed] [Google Scholar]
  42. Ribeiro Teresa Gonçalves, Izdebski Radosław, Urbanowicz Paweł, Carmeli Yehuda, Gniadkowski Marek, Peixe Luísa (2021). Citrobacter telavivum sp. nov. with chromosomal mcr‐9 from hospitalized patients. European Journal of Clinical Microbiology & Infectious Diseases, 40(1), 123–131. 10.1007/s10096-020-04003-6 [DOI] [PubMed] [Google Scholar]
  43. Sacramento, A. G. , Fernandes, M. R. , Sellera, F. P. , Muñoz, M. E. , Vivas, R. , Dolabella, S. S. , & Lincopan, N. (2018). Genomic analysis of MCR‐1 and CTX‐M‐8 co‐producing Escherichia coli ST58 isolated from a polluted mangrove ecosystem in Brazil. Journal of Global Antimicrobial Resistance, 15, 288–289. 10.1016/j.jgar.2018.10.024 [DOI] [PubMed] [Google Scholar]
  44. Sadek, M. , Nariya, H. , Shimamoto, T. , Kayama, S. , Yu, L. , Hisatsune, J. , Sugai, M. , Nordmann, P. , Poirel, L. , & Shimamoto, T. (2020). First genomic characterization of blaVIM‐1 and mcr‐9‐coharbouring Enterobacter hormaechei isolated from food of animal origin. Pathogens, 9(9), E687. 10.3390/pathogens9090687 [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Saidenberg, A. , Stegger, M. , Price, L. B. , Johannesen, T. B. , Aziz, M. , Cunha, M. , & Knöbl, T. (2020). mcr‐Positive Escherichia coli ST131‐H22 from poultry in Brazil. Emerging Infectious Diseases, 26(8), 1951–1954. 10.3201/eid2608.191724 [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sekyere, J. O. , Maningi, N. E. , Modipane, L. , & Mbelle, N. M. (2020). Emergence of mcr‐9.1 in extended‐spectrum‐β‐lactamase‐producing clinical enterobacteriaceae in Pretoria, South Africa: global evolutionary phylogenomics, resistome, and mobilome. mSystems, 5(3), e00148‐20.doi: 10.1128/mSystems.00148‐20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sellera, F. P. , Fernandes, M. R. , Moura, Q. , Carvalho, M. , & Lincopan, N. (2018). Extended‐spectrum‐β‐lactamase (CTX‐M)‐producing Escherichia coli in wild fishes from a polluted area in the Atlantic Coast of South America. Marine Pollution Bulletin, 135, 183–186. 10.1016/j.marpolbul.2018.07.012 [DOI] [PubMed] [Google Scholar]
  48. Sellera, F. P. , Fernandes, M. R. , Moura, Q. , Souza, T. A. , Cerdeira, L. , & Lincopan, N. (2017). Draft genome sequence of Enterobacter cloacae ST520 harbouring bla KPC‐2, bla CTX‐M‐15 and bla OXA‐17 isolated from coastal waters of the South Atlantic Ocean. Journal of Global Antimicrobial Resistance, 10, 279–280. 10.1016/j.jgar.2017.07.017 [DOI] [PubMed] [Google Scholar]
  49. Sellera, F. P. , Fernandes, M. R. , Sartori, L. , Carvalho, M. P. , Esposito, F. , Nascimento, C. L. , Dutra, G. H. , Mamizuka, E. M. , Pérez‐Chaparro, P. J. , McCulloch, J. A. & Lincopan, N. (2017). Escherichia coli carrying IncX4 plasmid‐mediated mcr‐1 and bla CTX‐M genes in infected migratory Magellanic penguins (Spheniscus magellanicus). Journal of Antimicrobial Chemotherapy, 72(4), 1255–1256. 10.1093/jac/dkw543 [DOI] [PubMed] [Google Scholar]
  50. Sevilla, E. , Marín, C. , Delgado‐Blas, J. F. , González‐Zorn, B. , Vega, S. , Kuijper, E. , Bolea, R. & Mainar‐Jaime, R. C. (2020). Wild griffon vultures (Gyps fulvus) fed at supplementary feeding stations: Potential carriers of pig pathogens and pig‐derived antimicrobial resistance? Transboundary and Emerging Diseases, 67(3), 1295–1305. 10.1111/tbed.13470 [DOI] [PubMed] [Google Scholar]
  51. Soliman, A. M. , Maruyama, F. , Zarad, H. O. , Ota, A. , Nariya, H. , Shimamoto, T. , & Shimamoto, T. (2020). Emergence of a multidrug‐resistant Enterobacter hormaechei clinical isolate from Egypt co‐harboring mcr‐9 and blaVIM‐4. Microorganisms, 8(4), 595. 10.3390/microorganisms8040595 [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Sucunza, F. , Danilewicz, D. , Cremer, M. , Andriolo, A. , & Zerbini, A. N. (2018). Refining estimates of availability bias to improve assessments of the conservation status of an endangered dolphin. PLoS One, 13(3), e0194213. 10.1371/journal.pone.0194213 [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Tsui, C. , Sundararaju, S. , Al Mana, H. , Hasan, M. R. , Tang, P. , & Perez‐Lopez, A. (2020). Draft genome sequence of an extended‐spectrum β‐lactamase‐producing Klebsiella oxytoca strain bearing mcr‐9 from Qatar. Microbiology Resource Announcements, 9(23), e00429–e520. 10.1128/MRA.00429-20 [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Tyson, G. H. , Li, C. , Hsu, C. H. , Ayers, S. , Borenstein, S. , Mukherjee, S. , Tran, T. T. , McDermott, P. F. & Zhao, S. (2020). The mcr‐9 gene of Salmonella and Escherichia coli is not associated with colistin resistance in the United States. Antimicrobial Agents and Chemotherapy, 64(8), e00573–e620. 10.1128/AAC.00573-20 [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Wang, C. , Feng, Y. , Liu, L. , Wei, L. , Kang, M. , & Zong, Z. (2020). Identification of novel mobile colistin resistance gene mcr‐10 . Emerging Microbes and Infections, 9(1), 508–516. 10.1080/22221751.2020.1732231 [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Wang, Y. , Liu, F. , Hu, Y. , Zhang, G. , Zhu, B. , & Gao, G. F. (2020). Detection of mobile colistin resistance gene mcr‐9 in carbapenem‐resistant Klebsiella pneumoniae strains of human origin in Europe. The Journal of Infection, 80(5), 578–606. 10.1016/j.jinf.2019.12.016 [DOI] [PubMed] [Google Scholar]
  57. White, A. , & Hughes, J. M. (2019). Critical importance of a One Health approach to antimicrobial resistance. EcoHealth, 16(3), 404–409. 10.1007/s10393-019-01415-5 [DOI] [PubMed] [Google Scholar]
  58. Yuan, Y. , Li, Y. , Wang, G. , Li, C. , Xiang, L. , She, J. , Yang, Y. , Zhong, F. & Zhang, L. (2019). Coproduction of MCR‐9 and NDM‐1 by colistin‐resistant Enterobacter hormaechei isolated from bloodstream infection. Infection and Drug Resistance, 12, 2979–2985. 10.2147/IDR.S217168 [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Zankari, E. , Hasman, H. , Cosentino, S. , Vestergaard, M. , Rasmussen, S. , Lund, O. , Aarestrup, F. M. , & Larsen, M. V. (2012). Identification of acquired antimicrobial resistance genes. The Journal of Antimicrobial Chemotherapy, 67, 2640–2644. 10.1093/jac/dks261 [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Zerbini, A. N. , Secchi, E. , Crespo, E. , Danilewicz, D. , & Reeves, R. (2017). Pontoporia blainvillei . The IUCN Red List of Threatened Species. 2017: e.T17978A123792204. Available: www.iucnredlist.org. Accessed 20 August 2020.

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Material

Click here for additional data file. (626.5KB, docx)

Data Availability Statement

The whole genome nucleotide sequence of the E. kobei E11R isolate is available in the GenBank database under accession number PRJNA615090. Additionally, genomic data of E. kobe E11R strain will be available in the OneBR platform (http://onehealthbr.com/) under the accession number OneBR‐ER1.

Articles from Transboundary and Emerging Diseases are provided here courtesy of Wiley

RESOURCES