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146 Virulence Volume 2 Issue 1
published theory on the mechanism of
action of bactericidal antibiotics suggests
that they share a common pathway in
bacterial killing involving the generation
of oxygen radicals, through the interfer-
ence of such antibiotics with the bacte-
From this model, it
can be predicted that mutations in genes
coding for proteins involved in the bacte-
rial metabolism might be relevant in the
development of resistance or supersuscep-
tibility. Unfortunately, our results did not
support a general role of oxygen radicals
in killing. Indeed although some of the
mutations analyzed in our work were pre-
viously found to be involved in the intrin-
sic resistance of P. aeruginosa to other
drugs, most of the mutants were speciﬁc,
indicating that the mechanisms of activ-
ity of the antibiotics and thus the mecha-
nisms of intrinsic resistance are not as
general as might be expected based on the
common pathway concept. Furthermore,
the percentage of mutants presenting the
same phenotype (increased or decreased
susceptibility) for imipenem and merope-
nem was not high, despite both antibiotics
being carbapenems. Another interesting
issue, raised as well in other studies on
is the ﬁnding of some
degree of strain-speciﬁcity. Whereas some
elements contributed to resistance in both
P. aeruginosa strains PAO1 and PA14,
others are strain-speciﬁc. This might be
due to different expression levels of these
elements in either of the strains or to the
existence of changes in their respective
metabolic and/or regulatory networks.
As a conclusion of our work, and con-
sistent with other published studies, it
can be stated that the intrinsic resistome
of P. aeruginosa involves a large array of
elements. Furthermore, the analysis of
mutants causing a reduced susceptibility
to b-lactams indicates that this bacte-
rial species has a high potential to evolve
towards resistance. Given that mutation
is the main mechanism whereby P. aeru-
ginosa develops resistance during chronic
the results presented in
our article and others dealing with the
intrinsic resistome of this bacterial patho-
gen might help to deﬁne novel elements
involved in the acquisition of resistance
during such infections.
Research in JLM laboratory was supported
by BIO2008-00090 from the Spanish
Ministerio de Ciencia e Innovación,
and KBBE-227258 (BIOHYPO) and
HEALTH-F3-2010-241476 (PAR) from
European Union. REWH was supported by
the Canadian Cystic Fibrosis Foundation.
CA is the recipient of a JAE contract from
CSIC. JO is the recipient of a fellowship
from Programa Beca Chile, CONICYT.
REWH holds a Canada Research
Chair. IW thanks the Juergen Manchot
Foundation and the Mukoviszidose e.V.,
Bonn, Germany (German Cystic Fibrosis
Association), for ﬁnancial support.
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