Abstract
BackgroundPasteurella multocida is a gram-negative bacterial pathogen that has a broad host range. One of the diseases it causes is fowl cholera in poultry. The availability of the genome sequence of avian P. multocida isolate Pm70 enables the application of functional genomics for observing global gene expression in response to a given stimulus. We studied the effects of three classes of antibiotics on the P. multocida transcriptome using custom oligonucleotide microarrays from NimbleGen Systems. Hybridizations were conducted with RNA isolated from three independent cultures of Pm70 grown in the presence or absence of sub-minimum inhibitory concentration (sub-MIC) of antibiotics. Differentially expressed (DE) genes were identified by ANOVA and Dunnett's test. Biological modeling of the differentially expressed genes (DE) was conducted based on Clusters of Orthologous (COG) groups and network analysis in Pathway Studio.ResultsThe three antibiotics used in this study, amoxicillin, chlortetracycline, and enrofloxacin, collectively influenced transcription of 25% of the P. multocida Pm70 genome. Some DE genes identified were common to more than one antibiotic. The overall transcription signatures of the three antibiotics differed at the COG level of the analysis. Network analysis identified differences in the SOS response of P. multocida in response to the antibiotics.ConclusionThis is the first report of the transcriptional response of an avian strain of P. multocida to sub-lethal concentrations of three different classes of antibiotics. We identified common adaptive responses of P. multocida to antibiotic stress. The observed changes in gene expression of known and putative P. multocida virulence factors establish the molecular basis for the therapeutic efficacy of sub-MICs. Our network analysis demonstrates the feasibility and limitations of applying systems modeling to high throughput datasets in 'non-model' bacteria.
Highlights
Pasteurella multocida is a gram-negative bacterial pathogen that has a broad host range
Expressed genes Statistical analysis of microarray data revealed that 1/4 Minimum inhibitory concentrations (MICs) of AMX, CTC, and ENR resulted in significant changes in expression of approximately 25% of the genome (525 genes, Additional file 1, supplemental table 1)
Instead of choosing a pre-determined threshold for determining the biological relevance of changes in gene expression, we considered every significant change in expression to be a valid change based on our rigorous statistical testing
Summary
Pasteurella multocida is a gram-negative bacterial pathogen that has a broad host range. The availability of the genome sequence of avian P. multocida isolate Pm70 enables the application of functional genomics for observing global gene expression in response to a given stimulus. Pasteurella multocida is a gram–negative bacterial pathogen that has a unique history of serving as a model species for new discoveries. In his seminal experiments in the late eighteenth century, Louis Pasteur demonstrated both attenuation as well as protective immune response utilizing P. multocida in birds [1,2]. The genome sequence has enabled subsequent functional genomics research with this species [79] It has enabled investigations on the proteomic and transcriptomic response of P. multocida Pm70 to subMICs of antibiotics [10,11,12]
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