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Volume 60, Issue 2

Effect of frameshift mutagen acriflavine on control of resistance genes in Free

Abstract

is a Gram-negative pathogenic bacterium that often exhibits a multidrug-resistant phenotype causing infections at various sites of the body and increasingly leading to septicaemic shock. This study evaluated the role of acriflavine, a frameshift mutagen, on the movement of insertion sequence IS in clinical isolates of , with the focus on changes in expression levels of the and genes. Resistance profiles were assessed with consideration of IS acting as a promoter upstream of the or gene. IS movement was observed in the acriflavine mutants Ab153M and Ab1225M. Ab153M exhibited an increase in the MIC values of carbapenems and ceftazidime, with IS gained upstream of the and genes, correlating with an increase in gene expression. Reduced expression of the 17, 23 and 25 kDa outer-membrane proteins (OMPs) was also observed in Ab153M. There was a significant decrease in MIC values of carbapenems with the loss of IS upstream of the and genes in strain Ab1225M, and a significant decrease in gene expression and, to a lesser extent, in expression. Ab1225M and a serially subcultured Ab1225 strain (Ab1225s) exhibited overexpression of the 17, 23, 25 and 27 kDa OMPs. There was a decrease in MIC values of the carbapenems and piperacillin/tazobactam but not of ceftazidime in Ab1225s, which had IS upstream of the and genes. A significant decrease in expression was observed in Ab1225s, whereas the expression of was similar to that in the Ab1225 parental strain. The attenuation in this strain may be due to overexpression of OMPs and it is clear that, even if IS is present upstream of an antibiotic resistance gene, it may not necessarily contribute towards the overexpression of antibiotic resistance genes ( in Ab1225s). Movement of the IS element within the chromosome may be an important regulatory mechanism employed by the bacterium under particular stress conditions, and the ability to upregulate the expression of antibiotic resistance genes is likely to be an important factor in the pathogenicity of this bacterium.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): OMP, outer-membrane protein
SGM
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2011-02-01
2024-04-20
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References

  1. Andrews J. M. 2007; BSAC standardized disc susceptibility testing method (version 6). J Antimicrob Chemother 60:20–41 [CrossRef]
     [Google Scholar]
  2. Anonymous. 1991; A guide to sensitivity testing. Report of the Working Party on Antibiotic Sensitivity Testing of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 27 (Suppl. D):1–50
     [Google Scholar]
  3. Aubert D., Naas T., Héritier C., Poirel L., Nordmann P. 2006; Functional characterization of IS 1999 , an IS 4 family element involved in mobilization and expression of β -lactam resistance genes. J Bacteriol 188:6506–6514 [CrossRef]
     [Google Scholar]
  4. Bossi L., Bossi-Figueroa N. 2007; A small RNA downregulates LamB maltoprotein in Salmonella . Mol Microbiol 65:799–810 [CrossRef]
     [Google Scholar]
  5. Brown S., Amyes S. G. B. 2006; OXA β -lactamases in Acinetobacter ; the story so far. J Antimicrob Chemother 57:1–3
     [Google Scholar]
  6. Chen C.-C., Hu S.-T. 2006; Two frameshift products involved in the transposition of bacterial insertion sequence IS 629 . J Biol Chem 281:21617–21628 [CrossRef]
     [Google Scholar]
  7. Corvec S., Caroff N., Espaze E., Giraudeau C., Drugeon H., Reynaud A. 2003; AmpC cephalosporinase hyperproduction in Acinetobacter baumannii clinical strains. J Antimicrob Chemother 52:629–635 [CrossRef]
     [Google Scholar]
  8. Corvec S., Poirel L., Naas T., Drugeon H., Nordmann P. 2007; Genetics and expression of the carbapenem-hydrolyzing oxacillinase gene bla OXA-23 in Acinetobacter baumannii . Antimicrob Agents Chemother 51:1530–1533 [CrossRef]
     [Google Scholar]
  9. Dolzani L., Tonin E., Lagatolla C., Prandin L., Monti-Bragadin C. 1995; Identification of Acinetobacter isolates in the A. calcoaceticus – A. baumannii complex by restriction analysis of the 16S–23S rRNA intergenic spacer sequences. J Clin Microbiol 33:1108–1113
     [Google Scholar]
  10. Fournier P. E., Richet H. 2006; The epidemiology and control of Acinetobacter baumannii in health care facilities. Clin Infect Dis 42:692–699 [CrossRef]
     [Google Scholar]
  11. Héritier C., Poirel L., Fournier P.-E., Claverie J.-M., Raoult D., Nordmann P. 2005; Characterization of the naturally occurring oxacillinase of Acinetobacter baumannii . Antimicrob Agents Chemother 49:4174–4179 [CrossRef]
     [Google Scholar]
  12. Hunt D. E., Sandham H. J. 1969; Improved agar gradient-plate technique. Appl Microbiol 17:329–330
     [Google Scholar]
  13. Kornberg A. 1980 DNA Replication San Francisco, USA: W. H. Freeman and Co;
     [Google Scholar]
  14. Lin L., Ling B.-D., Li X.-Z. 2009; Distribution of the multidrug efflux pump genes, adeABC , adeDE and adeIJK , and class 1 integron genes in multiple-antimicrobial-resistant clinical isolates of Acinetobacter baumannii–Acinetobacter calcoaceticus complex. Int J Antimicrob Agents 33:27–32 [CrossRef]
     [Google Scholar]
  15. Mahillon J., Chandler M. 1998; Insertion sequences. Microbiol Mol Biol Rev 62:725–774
     [Google Scholar]
  16. Mugnier P. D., Poirel L., Nordmann P. 2009; Functional analysis of insertion sequence IS Aba1 , responsible for genomic plasticity of Acinetobacter baumannii . J Bacteriol 191:2414–2418 [CrossRef]
     [Google Scholar]
  17. Nagai T., Phan Tran L. S., Inatsu Y., Itoh Y. 2000; A new IS 4 family insertion sequence, IS 4Bsu1 , responsible for genetic instability of poly- γ -glutamic acid production in Bacillus subtilis . J Bacteriol 182:2387–2392 [CrossRef]
     [Google Scholar]
  18. Nikaido H. 2003; Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 67:593–656 [CrossRef]
     [Google Scholar]
  19. Peleg A. Y., Seifert H., Paterson D. L. 2008; Acinetobacter baumannii : emergence of a successful pathogen. Clin Microbiol Rev 21:538–582 [CrossRef]
     [Google Scholar]
  20. Perez F., Hujer A. M., Hujer K. M., Decker B. K., Rather P. N., Bonomo R. A. 2007; Global challenge of multidrug-resistant Acinetobacter baumannii . Antimicrob Agents Chemother 51:3471–3484 [CrossRef]
     [Google Scholar]
  21. Rodríguez-Martínez J.-M., Nordmann P., Ronco E., Poirel L. 2010; Extended-spectrum cephalosporinase in Acinetobacter baumannii . Antimicrob Agents Chemother 54:3484–3488 [CrossRef]
     [Google Scholar]
  22. Ruiz M., Marti S., Fernandez-Cuenca F., Alvaro P., Vila J. 2007; Prevalence of IS Aba1 in epidemiologically unrelated Acinetobacter baumannii clinical isolates. FEMS Microbiol Lett 274:63–66 [CrossRef]
     [Google Scholar]
  23. Spelman D. W. 2002; Hospital-acquired infections. Med J Aust 176:286–291
     [Google Scholar]
  24. Vila J., Martí S., Sánchez-Céspedes J. 2007; Porins, efflux pumps and multidrug resistance in Acinetobacter baumannii . J Antimicrob Chemother 59:1210–1215 [CrossRef]
     [Google Scholar]
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Effect of frameshift mutagen acriflavine on control of resistance genes in Acinetobacter baumannii
J. Med. Microbiol. 60, 211 (2011); https://doi.org/10.1099/jmm.0.025544-0
/content/journal/jmm/10.1099/jmm.0.025544-0
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