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Antimicrobial Agents and Chemotherapy, October 2001, p. 2975-2976, Vol. 45, No. 10
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.10.2975-2976.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
LETTERS TO THE EDITOR
Interspecies Transfer of Antibiotic Resistance between
Helicobacter pylori and Helicobacter
acinonychis
 |
LETTER |
Helicobacter pylori is a gram-negative microaerophilic
bacterium that causes chronic gastritis and peptic ulcer disease in humans and is associated with gastric cancer. Antibiotic resistance in
H. pylori is a major cause of therapy failure. In general, bacteria can acquire antibiotic resistance either by spontaneous mutation or by horizontal transfer of resistance genes. A possible mechanism for acquisition of antibiotic resistance by H. pylori is genetic transformation (7). Recently, the
mechanism for transformation of H. pylori was suggested to
be specific for DNA of members of the genus Helicobacter
(6). This proposed genus-specific DNA uptake led us to
investigate whether interspecies transfer of antibiotic resistance can
take place in Helicobacter.
Previously, metronidazole resistance was reported for
Helicobacter acinonychis isolates from captive tigers with
ulcers (1). We observed that the H. acinonychis reference isolate (NCTC12686) and H. acinonychis isolate Sheeba (2) both consisted of a
large metronidazole-sensitive subpopulation and a small
metronidazole-resistant subpopulation. By repetitive subculture of
colonies of each subpopulation, both homogeneous
metronidazole-sensitive isolates (designated NCTC12686 MtzS and
Sheeba MtzS) and fully metronidazole-resistant isolates (NCTC12686 MtzR
and Sheeba MtzR; MICs for both were >256 µg/ml) were obtained. DNA
was isolated from the metronidazole-resistant strains Sheeba MtzR and
NCTC12686 MtzR and used for transformation of two
metronidazole-sensitive H. pylori strains through natural transformation, essentially as described by Wang et al.
(9). Metronidazole-resistant transformants were obtained
for both H. pylori strains (Table
1). In contrast, no
metronidazole-resistant colonies were obtained in a mock transformation
with phosphate-buffered saline (Table 1).
Conversely, the metronidazole-sensitive H. acinonychis
strains Sheeba MtzS and NCTC12686 MtzS could be transformed to
metronidazole resistance with chromosomal DNA isolated from two
H. pylori strains which are metronidazole resistant due to
known mutations that inactivate the rdxA nitroreductase gene
(Table 1). Type strain NCTC11637 is resistant due to a
transposon-induced deletion in rdxA (4); the
metronidazole-resistant variant of strain 1061 (1061 MtzR) contains the
null mutation containing rdxA of strain 439 (5). Transformation with this DNA resulted in high numbers of transformants, in contrast to control transformations
(phosphate-buffered saline without DNA), which did not yield any
metronidazole-resistant colonies. Additional evidence for interspecies
DNA transfer comes from transformation with plasmid pRdxA, which
contains a disrupted H. pylori-derived rdxA gene
(8). Transformation of H. acynonychis with
pRdxA resulted in similar numbers of transformants (Table 1).
Interspecies transformation was not limited to metronidazole
resistance, as both H. acinonychis strains could be readily
transformed to clarithromycin resistance. Both chromosomal DNA of the
clarithromycin-resistant variant of strain 1061 (1061 MtzR/ClaR)
(8), which is clarithromycin resistant due to a
single base pair mutation (A2142-G) in the 23S ribosomal
RNA gene (rDNA) (3), and an 850-bp PCR product of the 23S
rDNA of this strain transformed both H. acinonychis strains
to a clarithromycin-resistant phenotype (Table 1).
In conclusion, we provide evidence that (i) H. acinonychis
is competent for natural transformation and (ii) H. pylori
can acquire antibiotic resistance by uptake of DNA from other
Helicobacter species and vice versa. To what extent
interspecies gene transfer contributes to antibiotic resistance in the
genus Helicobacter depends on the relative frequencies of
intraspecies transfer, interspecies transfer, and mutation rate in
vivo, which remain to be investigated.
| |
FOOTNOTES |
*
Phone: 31-10-463-2982
Fax: 31-10-463-4682
E-mail: Kusters{at}MDL.AZR.NL
| |
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| | | | |
R. G. J. Pot
J. G. Kusters*
Department of Gastroenterology and Hepatology
Dijkzigt Hospital
Dr. Molewaterplein 40, Room L481
3015 GD Rotterdam, The
Netherlands
|
| | | | |
L. C. Smeets
W. Van
Tongeren
C. M. J. E. Vandenbroucke-Grauls
Department of Medical Microbiology and Infection Control
Vrije Universiteit Medical Center
Amsterdam, The Netherlands
|
| | | | |
A. Bart
Department of Medical Microbiology
Academic Medical Center
Amsterdam, The Netherlands
|
Antimicrobial Agents and Chemotherapy, October 2001, p. 2975-2976, Vol. 45, No. 10
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.10.2975-2976.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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