David A. Small

Microarray analysis of Pseudomonas aeruginosa reveals induction of pyocin genes in response to hydrogen peroxide

BackgroundPseudomonas aeruginosa, a pathogen infecting those with cystic fibrosis, encounters toxicity from phagocyte-derived reactive oxidants including hydrogen peroxide during active infection. P. aeruginosa responds with adaptive and protective strategies against these toxic species to effectively infect humans. Despite advances in our understanding of the responses to oxidative stress in many specific cases, the connectivity between targeted protective genes and the rest of cell metabolism remains obscure.ResultsHerein, we performed a genome-wide transcriptome analysis of the cellular responses to hydrogen peroxide in order to determine a more complete picture of how oxidative stress-induced genes are related and regulated.Our data reinforce the previous conclusion that DNA repair proteins and catalases may be among the most vital antioxidant defense systems of P. aeruginosa. Our results also suggest that sublethal oxidative damage reduces active and/or facilitated transport and that intracellular iron might be a key factor for a relationship between oxidative stress and iron regulation. Perhaps most intriguingly, we revealed that the transcription of all F-, R-, and S-type pyocins was upregulated by oxidative stress and at the same time, a cell immunity protein (pyocin S2 immunity protein) was downregulated, possibly leading to self-killing activity.ConclusionThis finding proposes that pyocin production might be another novel defensive scheme against oxidative attack by host cells.

Comparative global transcription analysis of sodium hypochlorite, peracetic acid, and hydrogen peroxide on Pseudomonas aeruginosa.

Disinfectants are routinely used in hospitals and health care facilities for surface sterilization. However, the mechanisms by which these disinfectants kill and the extent to which bacteria, including Pseudomonas aeruginosa, are resistant remains unclear. Consequently, P. aeruginosa nosocomial infections result in considerable casualties and economic hardship. Previously, DNA microarrays were utilized to analyze the genome-wide transcription changes in P. aeruginosa after oxidative antimicrobial (sodium hypochlorite, peracetic acid, and hydrogen peroxide) exposure. Simultaneous analysis of these transcriptome datasets provided a comprehensive understanding of the differential responses to these disinfectants. An analysis of variance, functional classification analysis, metabolic pathway analysis, Venn diagram analysis, and principal component analysis revealed that sodium hypochlorite exposure resulted in more genome-wide changes than either peracetic acid or hydrogen peroxide exposures.

Toxicogenomic analysis of sodium hypochlorite antimicrobial mechanisms in Pseudomonas aeruginosa

Sodium hypochlorite (bleach) is routinely used in hospitals and health care facilities for surface sterilization; however, the mechanism of action by which this disinfectant kills and the extent to which Pseudomonas aeruginosa is resistant to sodium hypochlorite have not been elucidated. Consequently, nosocomial infections from P. aeruginosa result in considerable casualties and economic hardship. We report the genome-wide transcriptome response of P. aeruginosa to sodium hypochlorite-induced oxidative stress via the use of DNA microarrays. In addition to a general oxidative stress response, our data revealed a downregulation of virtually all genes related to oxidative phosphorylation and electron transport and an upregulation of many organic sulfur transport and metabolism genes.