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Infection and Immunity, July 2008, p. 3357, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00479-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

LETTER TO THE EDITOR

Dual Spectinomycin-Streptomycin Resistance Marker in Brucella spp.


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LETTER
 
Pathogenic microbiology investigators have a responsibility to consider the public health implications of their research, including the experimental introduction of antibiotic resistance markers that could influence the treatment of infectious diseases. Furthermore, the reviewers for Infection and Immunity as well as other scientific journals are asked to evaluate submitted manuscripts for the occurrence of "misuses of microbiology or of information derived from microbiology"(1). But the importance of resistance to multiple antibiotics conferred by single marker genes is not always recognized. A case in point is the bacterial aadA1 gene in the omega fragment, originally from plasmid R100.1 (6). The use of this marker has recently been reported for gene disruption in Brucella suis with selection for resistance against spectinomycin, an antibiotic not used in the treatment of brucellosis (5). However, this marker also confers resistance to streptomycin, a frontline antibiotic frequently included in therapeutic protocols for brucellosis (2). This point may be particularly important for this organism due to its status as a relatively frequent cause of laboratory-acquired infection and its classification as a risk group 3 pathogen, a CDC select agent, and a USDA high-consequence livestock pathogen (3, 4, 7). There may be implications for other investigators considering the use of the same marker or interested in obtaining the recombinant streptomycin-resistant Brucella strains reported in reference 5. Alternative markers not conferring resistance to streptomycin should be used or developed to avoid these problems associated with aadA1 in Brucella spp.


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FOOTNOTES
 
Editor: J. B. Bliska


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REFERENCES
 
    1
  1. American Society for Microbiology. 17 April 2008, accession date. Policy guidelines of the publications board of the ASM in the handling of manuscripts dealing with microbiological sensitive issues. http://journals.asm.org/misc/Pathogens_and_Toxins.shtml.
    2. 2
  2. Ariza, J., M. Bosilkovski, A. Cascio, J. D. Colmenero, M. J. Corbel, M. E. Falagas, Z. A. Memish, M. R. Roushan, E. Rubinstein, N. V. Sipsas, J. Solera, E. J. Young, and G. Pappas. 2007. Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations. PLoS Med. 4:e317.[CrossRef][Medline]
    3. 3
  3. National Institutes of Health. 2002. NIH guidelines for research involving recombinant DNA molecules. http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html.
    4. 4
  4. National Select Agent Registry. 2005. Select agent/toxin list. http://www.selectagents.gov/agentToxinList.htm.
    5. 5
  5. Posadas, D. M., F. A. Martín, J. V. Sabio y García, J. M. Spera, M. V. Delpino, P. Baldi, E. Campos, S. L. Cravero, and A. Zorreguieta. 2007. The TolC homologue of Brucella suis is involved in resistance to antimicrobial compounds and virulence. Infect. Immun. 75:379-389.[Abstract/Free Full Text]
    6. 6
  6. Prentki, P., and H. M. Krisch. 1984. In vitro insertional mutagenesis with a selectable DNA fragment. Gene 29:303-313.[CrossRef][Medline]
    7. 7
  7. U.S. Government Printing Office. 2007. Biosafety in microbiological and biomedical laboratories, 5th ed. U.S. Government Printing Office, Washington, DC.
Jon P. Woods
Department of Medical Microbiology & Immunology
University of Wisconsin
Madison, Wisconsin 53706-1532
Phone: (608) 265-6292
Fax: (608) 265-6717
E-mail: jpwoods{at}facstaff.wisc.edu


Author's Reply


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LETTER 
 
I agree that cassettes that do not provide cross-resistance to streptomycin, or, alternatively, unmarked deletion mutations, are more appropriate options for the inactivation of genes in Brucella spp. We are now avoiding the use of the spectinomycin cassette and have replaced it with an unmarked deletion mutation or another cassette.

Angeles Zorreguieta
Fundacion Instituto Leloir
CONICET and
University of Buenos Aires
Patricias Argentinas 435
Buenos Aires, Argentina
Phone: 54 11 52387500
Fax: 54 11 52387501
E-mail: azorreguieta{at}leloir.org.ar

Infection and Immunity, July 2008, p. 3357, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00479-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




This Article
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