Affiliation:
1. Department of Bacteriology, University of Wisconsin—Madison, Madison, Wisconsin, USA
2. Department of Biological Sciences, The George Washington University, Washington, DC, USA
3. Department of Microbiology, University of Tennessee—Knoxville, Knoxville, Tennessee, USA
Abstract
ABSTRACT
In the entomopathogenic bacterium
Xenorhabdus nematophila
, cell-to-cell variation in the abundance of the Lrp transcription factor leads to virulence modulation; low Lrp levels are associated with a virulent phenotype and suppression of antimicrobial peptides (AMPs) in
Manduca sexta
insects, while cells that lack
lrp
or express high Lrp levels are virulence attenuated and elicit AMP expression. To better understand the basis of these phenotypes, we examined
X. nematophila
strains expressing fixed Lrp levels. Unlike the
lrp
-null mutant, the high-
lrp
strain is fully virulent in
Drosophila melanogaster
, suggesting that these two strains have distinct underlying causes of virulence attenuation in
M. sexta
. Indeed, the
lrp
-null mutant was defective in cytotoxicity against
M. sexta
hemocytes relative to that in the high-
lrp
and low-
lrp
strains. Further, supernatant derived from the
lrp
-null mutant but not from the high-
lrp
strain was defective in inhibiting weight gain when fed to 1st instar
M. sexta
. These data suggest that contributors to the
lrp
-null mutant virulence attenuation phenotype are the lack of Lrp-dependent cytotoxic and extracellular oral growth inhibitory activities, which may be particularly important for virulence in
D. melanogaster
. In contrast, the high-Lrp strain was sensitive to the antimicrobial peptide cecropin, had a transient survival defect in
M. sexta
, and had reduced extracellular levels of insecticidal activity, measured by injection of supernatant into 4th instar
M. sexta
. Thus, high-
lrp
strain virulence attenuation may be explained by its hypersensitivity to
M. sexta
host immunity and its inability to secrete one or more insecticidal factors.
IMPORTANCE
Adaptation of a bacterial pathogen to host environments can be achieved through the coordinated regulation of virulence factors that can optimize success under prevailing conditions. In the insect pathogen
Xenorhabdus nematophila
, the global transcription factor Lrp is necessary for virulence when injected into
Manduca sexta
or
Drosophila melanogaster
insect hosts. However, high levels of Lrp, either naturally occurring or artificially induced, cause attenuation of
X. nematophila
virulence in
M. sexta
but not
D. melanogaster
. Here, we present evidence suggesting that the underlying cause of high-Lrp-dependent virulence attenuation in
M. sexta
is hypersensitivity to host immune responses and decreased insecticidal activity and that high-Lrp virulence phenotypes are insect host specific. This knowledge suggests that
X. nematophila
faces varied challenges depending on the type of insect host it infects and that its success in these environments depends on Lrp-dependent control of a multifactorial virulence repertoire.
Funder
United States-Israel Binational Agricultural Research and Development Fund
HHS | National Institutes of Health
National Science Foundation
Publisher
American Society for Microbiology
Subject
Ecology,Applied Microbiology and Biotechnology,Food Science,Biotechnology
Cited by
15 articles.
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