Spread and exchange of bla NDM-1 in hospitalized neonates: role of mobilizable genetic elements
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To investigate the mobilizable elements associated with bla NDM-1 in Enterobacteriaceae isolated from septicaemic neonates at a NICU in India, during December, 2008–2011. An attempt was also made to understand whether there was a pattern in the temporal acquisition of bla NDM-1 within the unit. Transferability of carbapenem resistance was tested by conjugation and transformation. Plasmid types and addiction systems were analysed. The genetic background of bla NDM-1 and association with class 1 integron were evaluated by PCR mapping. RFLP was carried out to discriminate plasmids of same incompatibility group. Transfer of carbapenem resistance was successful in 13/15 cases. bla NDM-1 was associated with different plasmid scaffolds (IncFII, IncL/M, IncN, IncR, IncHIB-M/FIB-M), IncF type being the prevalent one. Addiction systems ccdAB and hok/sok were associated with transferable plasmids. Genetic structures surrounding bla NDM-1 showed its association with at least a remnant of ISAba125 at its 5′-end. The spread of NDM-1 was not related to class 1 integron which possessed resistance determinants against trimethoprim (dfrA12, dfrA1, dfrA5), streptomycin (aadA2, aacA4), and rifampicin (arr-3). RFLP showed that three isolates possessed the same FII/FIIs plasmid; two of these three isolates were from a single neonate, implying interspecies transfer of bla NDM-1. The predominance of FII plasmids and ISAba125 along with bla NDM-1 was noted, but no specific pattern in the temporal acquisition of mobile genetic elements could be identified. To the best of our knowledge, this report is the first to inform the in-vivo interspecies plasmid transfer event of bla NDM-1 in a neonate.
KeywordsNeonatal Intensive Care Unit Meropenem Colistin Mobile Genetic Element Ertapenem
Compliance with ethical standards
The study was partially supported by Department of Science & Technology, West Bengal research grant and Indian Council of Medical Research (ICMR) intramural fund. Saswati Datta and Shravani Mitra were supported by fellowships from ICMR and Council of Scientific & Industrial Research (CSIR) respectively.
Conflict of interest
All authors report no conflicts of interest.
The study protocol was carefully reviewed and approved by the Institutional Ethics Committee of the National Institute of Cholera and Enteric Diseases (Indian Council of Medical Research) (No. C-48/2010 T & E, No. C-48/2011- T & E, and No. A-1/2016-IEC respectively).
Individual informed consent was waived because this study used currently existing samples collected during the course of routine diagnosis of sepsis and did not pose any additional risks to the patients. The patient records/information were anonymized and de-identified prior to analysis.
- 5.Sonnevend A, Al Baloushi A, Ghazawi A, Hashmey R, Girgis S, Hamadeh MB, Al Haj M, Pál T (2013) Emergence and spread of NDM-1 producer Enterobacteriaceae with contribution of IncX3 plasmids in the United Arab Emirates. J Med Microbiol 62:1044–1050. doi: 10.1099/jmm.0.059014-0 CrossRefPubMedGoogle Scholar
- 6.Giske CG, Fröding I, Hasan CM, Turlej-Rogacka A, Toleman M, Livermore D, Woodford N, Walsh TR (2012) Diverse sequence types of Klebsiella pneumoniae contribute to the dissemination of bla NDM-1 in India, Sweden, and the United Kingdom. Antimicrob Agents Chemother 56:2735–2738. doi: 10.1128/AAC.06142-11 CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Day KM, Ali S, Mirza IA, Sidjabat HE, Silvey A, Lanyon CV, Cummings SP, Abbasi SA, Raza MW, Paterson DL, Perry JD (2013) Prevalence and molecular characterization of Enterobacteriaceae producing NDM-1 carbapenemase at a military hospital in Pakistan and evaluation of two chromogenic media. Diagn Microbiol Infect Dis 75:187–191CrossRefPubMedGoogle Scholar
- 13.Shibata N, Doi Y, Yamane K, Yagi T, Kurokawa H, Shibayama K, Kato H, Kai K, Arakawa Y (2003) PCR typing of genetic determinants for metallo-β-lactamases and integrases carried by gram negative bacteria isolated in Japan, with focus on the class 3 integron. J Clin Microbiol 41:5407–5413CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, Walsh TR (2009) Characterization of a new metallo-β-lactamase gene, bla NDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 53:5046–5054. doi: 10.1128/AAC.00774-09 CrossRefPubMedPubMedCentralGoogle Scholar