Abstract
The NpmA bacterial 16S rRNA methyltransferase, which is identified from Escherichia coli strains, confers high resistance to many types of aminoglycoside upon its host cells. But despite its resistance-conferring ability, only two cases of its isolation from E. coli (14 years apart) have been reported to date. Here, we investigated the effect of the npmA gene on aminoglycoside resistance in Pseudomonas aeruginosa and Klebsiella pneumoniae and its stability in E. coli cells by comparing it with armA, another 16S rRNA methyltransferase gene currently spreading globally. As a result, we found that npmA conferred resistance to all types of aminoglycoside antibiotics we tested (except streptomycin) in both P. aeruginosa and K. pneumoniae, as well in E. coli. In addition, co-expression of armA and npmA resulted in an additive effect for the resistance. However, in return for the resistance, we also observed that the growth rates and the cell survivability of the strains transformed with the npmA-harboring plasmids were inferior than those of the control strains and that these plasmids were easily disrupted by IS10, IS1, and IS5 insertion sequences. We discuss these data in the context of the threat posed by pathogenic strains possessing npmA.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
WHO. Antimicrobial resistance: global report on surveillance. http://apps.who.int/iris/bitstream/10665/112642/1/9789241564748_eng.pdf. 2014.
Al-Tawfiq JA, Laxminarayan R, Mendelson M. How should we respond to the emergence of plasmid-mediated colistin resistance in humans and animals? Int J Infect Dis. 2017;54:77–84.
Sheng WH, Badal RE, Hsueh PR, on behalf of the SMART Program. Distribution of extended-spectrum β-lactamases, AmpC β-lactamases, and carbapenemases among enterobacteriaceae isolates causing intra-abdominal infections in the Asia-Pacific region: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART). Antimicrob Agents Chemother. 2013;57:2981–8.
Galimand M, Courvalin P, Lambert T. Plasmid-mediated high-level resistance to aminoglycosides in Enterobacteriaceae due to 16S rRNA methylation. Antimicrob Agents Chemother. 2003;47:2565–71.
Wachino J, Arakawa Y. Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria: an update. Drug Resist Updat. 2012;15:133–48.
Sekizuka T, et al. Complete sequencing of the blaNDM-1-positive IncA/C plasmid from Escherichia coli ST38 isolate suggests a possible origin from plant pathogens. PLoS ONE. 2011;6:e25334 https://doi.org/10.1371/journal.pone.0025334.
Ho PL, et al. Complete sequencing of pNDM-HK encoding NDM-1 carbapenemase from a multidrug-resistant Escherichia coli strain isolated in Hong Kong. PLoS ONE. 2011;6:e17989 https://doi.org/10.1371/journal.pone.0017989.
Waterman PE, et al. Bacterial peritonitis due to Acinetobacter baumannii sequence type 25 with plasmid-borne New Delhi metallo-β-lactamase in Honduras. Antimicrob Agents Chemother. 2013;57:4584–6.
Beauclerk AAD, Cundliffe E. Sites of action of two ribosomal RNA methylases responsible for resistance to aminoglycosides. J Mol Biol. 1987;193:661–71.
Wachino J, et al. Novel plasmid-mediated 16S rRNA m1A1408 methyltransferase, NpmA, found in a clinically isolated Escherichia coli strain resistant to structurally diverse aminoglycosides. Antimicrob Agents Chemother. 2007;51:4401–9.
Zhao Z, et al. Evaluation of automated systems for aminoglycosides and fluoroquinolones susceptibility testing for Carbapenem-resistant. Enterobact Antimicrob Resist Infect Control. 2017;6:77 https://doi.org/10.1186/s13756-017-0235-7.
Demirci H, et al. A structural basis for streptomycin-induced misreading of the genetic code. Nat Commun. 2013;4:1355 https://doi.org/10.1038/ncomms2346
Casacuberta E, González J. The impact of transposable elements in environmental adaptation. Mol Ecol. 2013;22:1503–17.
Stoebel DM, Dorman CJ. The effect of mobile element IS10 on experimental regulatory evolution in Escherichia coli. Mol Biol Evol. 2010;27:2105–12.
Chou HH, Berthet J, Marx CJ. Fast growth increases the selective advantage of a mutation arising recurrently during evolution under metal limitation. PLoS Genet. 2009;5:e1000652 https://doi.org/10.1371/journal.pgen.1000652.
Gaffé J, et al. Insertion sequence-driven evolution of Escherichia coli in chemostats. J Mol Evol. 2011;72:398–412.
Pósfai G, et al. Emergent properties of reduced-genome Escherichia coli. Science. 2006;312:1044–6.
Szpirer CY, Faelen M, Couturier M. Mobilization function of the pBHR1 plasmid, a derivative of the broad-host-range plasmid pBBR1. J Bacteriol. 2001;183:2101–10.
Merrick MJ, Gibbins JR, Postgate JR. A rapid and efficient method for plasmid transformation of Klebsiella pneumoniae and Escherichia coli. J Gen Microbiol. 1987;133:2053–7.
Dennis JJ, Sokol PA. Electrotransformaiton of Pseudomonas. Methods Mol Biol. 1995;47:125–33.
den Dunnen JT, et al. HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutat. 2016;37:564–9.
Acknowledgements
We thank Ms. Sayaka Takahashi for technical assistance. This work is partially supported by Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development, AMED (16fk0108120j0001).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Ishizaki, Y., Shibuya, Y., Hayashi, C. et al. Instability of the 16S rRNA methyltransferase-encoding npmA gene: why have bacterial cells possessing npmA not spread despite their high and broad resistance to aminoglycosides?. J Antibiot 71, 798–807 (2018). https://doi.org/10.1038/s41429-018-0070-y
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41429-018-0070-y
This article is cited by
-
Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria
Nature Communications (2025)
-
Cycloimidamicins, Novel natural lead compounds for translation inhibition in Pseudomonas aeruginosa
The Journal of Antibiotics (2023)
