Skip to main content

Advertisement

SpringerLink
Log in

Molecular Characteristics and Genetic Analysis of Extensively Drug-Resistant Isolates with different Tn3 Mobile Genetic Elements

  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

Extensively drug-resistant (XDR) bacteria are the main caues for causing clinical infectious diseases. Our aim was to distinguish the present molecular epidemiological situation of XDR Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli isolates recovered from local hospitals in Changzhou. Antibiotic susceptibility and phenotypic analysis, multilocus sequence typing and Pulsed Field Gel Electrophoresis were performed to trace these isolates. Resistant phenotype and gene analysis from 29 XDR strains demonstrated that they mainly included TEM, CTX-M-1/2, OXA-48, and KPC products. A. baumannii strains belonged to sequence type (ST) ST224, and carrying the blaCTX-M-2/TEM gene. The quinolone genes aac(6’)-ib-cr and qnrB were carrying only in A. baumannii and E.coli. Three (2.3%) of these strains were found to contain the blaNDM-1 or blaNDM-5 gene. A new genotype of K. pneumoniae was found as ST2639. Epidemic characteristics of the XDR clones showed that antibiotic resistance genes distributed unevenly in different wards in Changzhou’s local hospitals. With the sequencing of blaNDM carrying isolates, the plasmids often carrying a highly conservative Tn3-relavent mobile genetic element. The especially coupled insert sequence ISKox3 may be a distinctive resistance gene transfer loci. The genotypic diversity variation of XDRs suggested that tracking and isolating the sources of antibiotic resistance especially MBL-encoding genes such as blaNDM—will help manage the risk of infection by these XDRs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

Data used for the manuscript have been retrieved from published studies and other publications available online.

References

  1. Bassetti M, Righi E, Carnelutti A, Graziano E, Russo A (2018) Multidrug-resistant Klebsiella pneumoniae: challenges for treatment, prevention and infection control. Expert Rev Anti Infect Ther 16(10):749–761

    CAS  PubMed  Google Scholar 

  2. Huemer M, Mairpady Shambat S, Brugger SD, Zinkernagel AS (2020) Antibiotic resistance and persistence—implications for human health and treatment perspectives. EMBO Rep 21(12):e51034

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Mulani MS, Kamble EE, Kumkar SN, Tawre MS, Pardesi KR (2019) Emerging strategies to combat ESKAPE pathogens in the era of antimicrobial resistance: a review. Front Microbiol 10:539

    PubMed  PubMed Central  Google Scholar 

  4. Ma YX, Wang CY, Li YY, Li J, Wan QQ, Chen JH, Niu LN (2020) Considerations and caveats in combating ESKAPE pathogens against nosocomial infections. Adv Sci 7(1):1901872

    CAS  Google Scholar 

  5. Balandín B, Ballesteros D, Pintado V, Soriano-Cuesta C, Cid-Tovar I, Sancho-González M, Royuela A (2022) Multicentre study of ceftazidime/avibactam for Gram-negative bacteria infections in critically ill patients. Int J Antimicrob Agents 59(3):106536

    PubMed  Google Scholar 

  6. Bassetti M, Garau J (2021) Current and future perspectives in the treatment of multidrug-resistant Gram-negative infections. J Antimicrobial Chem 76(Supplement_4):iv23–iv37

    CAS  Google Scholar 

  7. van Duin D, Doi Y (2017) The global epidemiology of carbapenemase-producing Enterobacteriace-ae. Virulence 8(4):460–469

    PubMed  Google Scholar 

  8. Liu YY, Wang, et al (2016) Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 16(2):161–168

  9. Garg SK, Singh O, Juneja D, Tyagi N, Khurana AS, Qamra A, Barkate H (2017) Resurgence of polymyxin B for MDR/XDR gram-negative infections: an overview of current evidence. Crit Care Res Pract, 2017

  10. Karaiskos I, Galani I, Papoutsaki V, Galani L, Giamarellou H (2022) Carbapenemase producing Klebsiella pneumoniae: Implication on future therapeutic strategies. Expert Rev Anti Infect Ther 20(1):53–69

    CAS  PubMed  Google Scholar 

  11. Turton JF, Wright L, Underwood A, Witney AA, Chan YT, Al-Shahib A, Woodford N (2015) High-resolution analysis by whole-genome sequencing of an international lineage (sequence type 111) of Pseudomonas aeruginosa associated with metallo-carbapenemases in the United Kingdom. J Clin Microbiol 53(8):2622–2631

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Shimizu W, Kayama S, Kouda S, Ogura Y, Kobayashi K, Shigemoto N, Sugai M (2015) Persistence and epidemic propagation of a Pseudomonas aeruginosa sequence type 235 clone harboring an IS 26 composite transposon carrying the bla IMP-1 integron in Hiroshima, Japan, 2005 to 2012. Antimicrob Agents Chemother 59(5):2678–2687

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Roy Chowdhury P, Scott M, Worden P, Huntington P, Hudson B, Karagiannis T, Djordjevic SP (2016) Genomic islands 1 and 2 play key roles in the evolution of extensively drug-resistant ST235 isolates of Pseudomonas aeruginosa. Open Biol 6(3):150175

    PubMed  PubMed Central  Google Scholar 

  14. Giani T, Arena F, Pollini S et al (2018) Italian nationwide survey on Pseudomonas aeruginosa from invasive infections: activity of ceftolozane/tazobactam and comparators, and molecular epidemiology of carbapenemase producers. J Antimicrob Chemother 73(3):664–671

    CAS  PubMed  Google Scholar 

  15. Botelho J, Grosso F, Quinteira S, Brilhante M, Ramos H, Peixe L (2018) Two decades of bla VIM-2-producing Pseudomonas aeruginosa dissemination: an interplay between mobile genetic elements and successful clones. J Antimicrob Chemother 73(4):873–882

    CAS  PubMed  Google Scholar 

  16. Zhang AN, Li LG, Ma L, Gillings MR, Tiedje JM, Zhang T (2018) Conserved phylogenetic distribution and limited antibiotic resistance of class 1 integrons revealed by assessing the bacterial genome and plasmid collection. Microbiome 6(1):1–14

    Google Scholar 

  17. Pragasam AK, Veeraraghavan B, Bakthavatchalam YD, Gopi R, Aslam RF (2017). Strengths and limitations of various screening methods for carbapenem-resistant Enterobacteriaceae including new method recommended by Clinical and Laboratory Standards Institute, 2017: a tertiary care experience. Indian J Med Microbio 35(1):116–119

  18. Patidar N, Vyas N, Sharma S, Sharma B (2021) Phenotypic detection of carbapenemase production in carbapenem-resistant Enterobacteriaceae by modified hodge test and modified strip carba NP test. J Lab Physicians 13(01):014–021

    CAS  Google Scholar 

  19. Kim HK, Park JS, Sung H, Kim MN (2015) Further modification of the modified Hodge test for detecting metallo-β-lactamase-producing carbapenem-resistant Enterobacteriaceae. Ann Lab Med 35(3):298

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhao G, Wang J, Yao et al(2022) Alkaline lysis-recombinase polymerase amplification combined with CRISPR/Cas12a assay for the ultrafast visual identification of pork in meat products. Food Chem 383:132318

  21. Kazi M, Ajbani K, Tornheim JA, Shetty A, Rodrigues C (2019) Multiplex PCR to detect pAmpC β-lactamases among Enterobacteriaceae at a tertiary care laboratory in Mumbai. India Microbiol 165(2):246

    CAS  Google Scholar 

  22. Probst K, Nurjadi D, Heeg K, Frede AM, Dalpke AH, Boutin S (2021) Molecular detection of carbapenemases in Enterobacterales: a comparison of real-time multiplex PCR and whole-genome sequencing. Antibiotics 10(6):726

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhao X, Hu M, Zhang Q et al (2020) Characterization of integrons and antimicrobial resistance in Salmonella from broilers in Shandong, China. Poult Sci 99(12):7046–7054

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Timofte D, Dan M, Maciuca IE, Ciucu L, Dabija ER, Guguianu E, Panzaru CV (2015) Emergence of concurrent infections with colistin-resistant ESBL-positive Klebsiella pneumoniae and OXA-23-producing Acinetobacter baumannii sensitive to colistin only in a Romanian cardiac intensive care unit. Eur J Clin Microbiol Infect Dis 34:2069–2074

    CAS  PubMed  Google Scholar 

  25. Bezdicek M, Nykrynova M, Sedlar K et al (2021) Rapid high-resolution melting genotyping scheme for Escherichia coli based on MLST derived single nucleotide polymorphisms. Sci Rep 11(1):16572

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Xu H, Zhou HJ, Li XG, Du XL, Hu JR, Chen DK, Cui ZG (2021) Genomic subtyping of nosocomial transmission of carbapenem resistant Klebsiella pneumoniae. Zhonghua yu Fang yi xue za zhi [Chin J Prev Med] 55(4):512–516

    CAS  PubMed  Google Scholar 

  27. Adjei AY, Vasaikar SD, Apalata T, Okuthe EG, Songca SP (2021) Phylogenetic analysis of carbapenem-resistant Acinetobacter baumannii isolated from different sources using multilocus sequence typing scheme. Infect Genet Evol 96:105132

    CAS  PubMed  Google Scholar 

  28. Chen Y, Zhou Z, Jiang Y, Yu Y (2011) Emergence of NDM-1-producing Acinetobacter baumannii in China. J Antimicrob Chemother 66(6):1255–1259

    CAS  PubMed  Google Scholar 

  29. Karlowsky JA, Hoban DJ, Hackel MA, Lob SH, Sahm DF (2017) Resistance among Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal and urinary tract infections in Latin American countries: SMART 2013–2015. Braz J Infect Dis 21:343–348

    PubMed  PubMed Central  Google Scholar 

  30. Marra AR, WeyCastelo SB et al (2006) Nosocomial bloodstream infections caused by Klebsiella pneumoniae: impact of extended-spectrum β-lactamase (ESBL) production on clinical outcome in a hospital with high ESBL prevalence. BMC Infect Dis 6:1–8

    Google Scholar 

  31. Tumbarello M, Spanu T, Sanguinetti, et al (2006) Bloodstream infections caused by extended-spectrum-β-lactamase-producing Klebsiella pneumoniae: risk factors, molecular epidemiology, and clinical outcome. Antimicrob Agents Chemother 50(2):498–504

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Du J, Li P, Liu H, Lü D, Liang H, Dou Y (2014) Phenotypic and molecular characterization of multidrug resistant Klebsiella pneumoniae isolated from a university teaching hospital. China PloS one 9(4):e95181

    PubMed  Google Scholar 

  33. Shoeb E, Badar U, Akhter J, Shams H, Sultana M, Ansari MA (2012) Horizontal gene transfer of stress resistance genes through plasmid transport. World J Microbiol Biotechnol 28:1021–1025

    CAS  PubMed  Google Scholar 

  34. Dunn SJ, Connor C, McNally A (2019) The evolution and transmission of multi-drug resistant Escherichia coli and Klebsiella pneumoniae: the complexity of clones and plasmids. Curr Opin Microbiol 51:51–56

    CAS  PubMed  Google Scholar 

  35. Catalano A, Iacopetta D, Ceramella J et al (2022) Multidrug resistance (MDR): a widespread phenomenon in pharmacological therapies. Molecules 27(3):616

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang W, Zhao L, Hu Y, Dottorini T, Fanning S, Xu J, Li F (2020) Epidemiological study on prevalence, serovar diversity, multidrug resistance, and CTX-M-type extended-spectrum β-lactamases of Salmonella spp. from patients with diarrhea, food of animal origin, and pets in several provinces of China. Antimicrob Agents Chemother 64(7):e00092-e120

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Yang DK, Liang HJ et al (2015) Analysis of drug-resistant gene detection of blaOXA-like genes from Acinetobacter baumannii. Genet Mol Res 14(4):18999–19004

    CAS  PubMed  Google Scholar 

  38. Zhang J, Zhou K et al (2016) High prevalence of ESBL-producing Klebsiella pneumoniae causing community-onset infections in China. Front Microbiol 7:1830

    PubMed  PubMed Central  Google Scholar 

  39. Zhao Z, Lan F, Liu M et al (2017) Evaluation of automated systems for aminoglycosides and fluoroquinolones susceptibility testing for Carbapenem-resistant Enterobacteriaceae. Antimicrob Resist Infect Control 6(1):1–6

    CAS  Google Scholar 

  40. Jiang M, Liu L et al (2016) Molecular epidemiology of multi-drug resistant Acinetobacter baumannii Isolated in Shandong. China Front Microbiol 7:1687

    PubMed  Google Scholar 

  41. Xu X, Li, et al (2017) Molecular characterisations of integrons in clinical isolates of Klebsiella pneumoniae in a Chinese tertiary hospital. Microb Pathog 104:164–170

    CAS  PubMed  Google Scholar 

  42. Hu WS, Yao SM, Fung CP, Hsieh YP, Liu CP, Lin JF (2007) An OXA-66/OXA-51-like carbapenemase and possibly an efflux pump are associated with resistance to imipenem in Acinetobacter baumannii. Antimicrob Agents Chemother 51(11):3844–3852

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Azimi L, Talebi M, Pourshafie MR, Owlia P, Lari AR (2015) Characterization of carbapenemases in extensively drug resistance Acinetobacter baumannii in a burn care center in Iran. Int J Mol Cell Med 4(1):46

    PubMed  PubMed Central  Google Scholar 

  44. Wang S, Zhao SY et al (2016) Antimicrobial resistance and molecular epidemiology of Escherichia coli causing bloodstream infections in three hospitals in Shanghai. China PloS one 11(1):e0147740

    PubMed  Google Scholar 

  45. Jin Y, Song X et al (2017) Characteristics of carbapenemase-producing Klebsiella pneumoniae as a cause of neonatal infection in Shandong, China. Exp Ther Med 13(3):1117–1126

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Chen Y, Gao J, Zhang H, Ying C (2017) Spread of the bla OXA–23-containing TN 2008 in carbapenem-resistant Acinetobacter baumannii isolates grouped in CC92 from China. Front Microbiol 8:163

    PubMed  PubMed Central  Google Scholar 

  47. LiLan J et al (2014) Sequential isolation in a patient of Raoultella planticola and Escherichia coli bearing a novel IS CR1 element carrying blaNDM-1. PLoS ONE 9(3):e89893

    Google Scholar 

  48. Zhao Y, Wang L, Zhang Z, Feng J, Kang H, Fang L, Tong Y (2017) Structural genomics of pNDM-BTR harboring In191 and Tn 6360, and other bla NDM-carrying IncN1 plasmids. Future Microbiol 12(14):1271–1281

    CAS  PubMed  Google Scholar 

  49. Pál T, Ghazawi A, Darwish D, Villa L, Carattoli A, Hashmey R, Sonnevend Á (2017) Characterization of NDM-7 carbapenemase-producing Escherichia coli isolates in the Arabian Peninsula. Microb Drug Resist 23(7):871–878

    PubMed  Google Scholar 

  50. Paskova V, Medvecky M et al (2018) Characterization of NDM-encoding plasmids from Enterobacteriaceae recovered from Czech hospitals. Front Microbiol 9:1549

    PubMed  PubMed Central  Google Scholar 

  51. LiuLi X et al (2017) Molecular characterization of Escherichia coli isolates carrying mcr-1, fosA3, and extended-spectrum-β-lactamase genes from food samples in China. Antimicrob Agents Chemother 61(6):e00064-e117

    Google Scholar 

  52. Botelho J, Lood C, Partridge SR, Van Noort V, Lavigne R, Grosso F, Peixe L (2019) Combining sequencing approaches to fully resolve a carbapenemase-encoding megaplasmid in a Pseudomonas shirazica clinical strain. Emerg Microbes Infect 8(1):1186–1194

    PubMed  PubMed Central  Google Scholar 

  53. Szuplewska M, Czarnecki J, Bartosik D (2014) Autonomous and non-autonomous Tn 3-family transposons and their role in the evolution of mobile genetic elements. Mob Genet Elements 4(6):1–4

    PubMed  Google Scholar 

  54. Partridge SR, Kwong SM, Firth N, Jensen SO (2018) Mobile genetic elements associated with antimicrobial resistance. Clin Microbiol Rev 31(4):e00088-e117

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Partridge SR, Brown HJ, Stokes HW, Hall RM (2001) Transposons Tn 1696 and Tn 21 and their integrons In4 and In2 have independent origins. Antimicrob Agents Chemother 45(4):1263–1270

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study received financial support from the Key Laboratory Project of Changzhou City (CM20223016), Leading Talent of Changzhou “The 14th Five-Year Plan” High-Level Health Talents Training Project (2022CZLJ025), Top Talent of Changzhou “The 14th Five-Year Plan” High-Level Health Talents Training Project (2022CZBJ096), Changzhou health green seedling talent plan and Changzhou science and technology Foundation (CJ20210073,CJ20220237 and CJ20220158), Young Talent Project (CZQM2020113), Innovation project of Changzhou Medical Center (CMCB202217).

Author information

Author notes

  1. Jiazhen Wang and Xin Dong equally contributed to this work.

Authors and Affiliations

  1. School of Public Health, Xuzhou Medical University, Xuzhou, 221004, China

    Jiazhen Wang, Fengming Wang, Jingyue Gu & Bowen Tu

  2. Pathogenic Biological Laboratory, Changzhou Disease Control and Prevention Centre, Changzhou Medical Centre, Nanjing Medical University, Changzhou, 213000, Jiangsu, China

    Xin Dong, Fengming Wang, Jinyi Jiang, Ying Zhao, Jian Xu, Xujian Mao & Bowen Tu

Authors
  1. Jiazhen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xin Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fengming Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jinyi Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jingyue Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jian Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xujian Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bowen Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors made substantial contributions to the conception and writing of the manuscript. They have also read and agreed to the publication of the manuscript.

Corresponding author

Correspondence to Bowen Tu.

Ethics declarations

Conflict of interest

There is no conflict of interest regarding the publication of this paper.

Ethical Approval

Not applicable.

Code Availability

Not applicable.

Consent to Participate

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Dong, X., Wang, F. et al. Molecular Characteristics and Genetic Analysis of Extensively Drug-Resistant Isolates with different Tn3 Mobile Genetic Elements. Curr Microbiol 80, 246 (2023). https://doi.org/10.1007/s00284-023-03340-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00284-023-03340-x

Keywords

Search

Navigation