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Effect of hypochlorous acid solution on the eradication and prevention of Pseudomonas aeruginosa infection, serum biochemical variables, and cecum microbiota in rats.

ABSTRACT: In this study, hypochlorous acid solution, a weak acid, provided as drinking water to rats, was evaluated for its ability to eradicate and prevent Pseudomonas aeruginosa infection, while monitoring its simultaneous effect on serum biochemical variables and microbiota in the rat cecum. The results suggest that the solution could not eliminate the bacteria in the experimentally infected rats; however, the administration of a 10-parts-per-million (ppm) hypochlorous acid solution as drinking water was effective in inhibiting horizontal spread of P. aeruginosa infection among cage mates. Additionally, exposure to hypochlorous solution did not have any effect on serum biochemical variables of the rat including levels of total cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin, total bilirubin, lipase, amylase, urea nitrogen, total protein, calcium (Ca), phosphorus (P), sodium (Na), chlorine (Cl), except for potassium (K) levels. The most frequently isolated bacteria in the rat cecum included species belonging to Bacteroidales, Lactobacillus, Clostridiales, Erysipelotrichaceae, Akkermansia, Coriobacteriales, and Firmicutes. The ratio of the terminal restriction fragment length polymorphism (T-RFLP) peaks did not differ across rats administered with 5 and 10 ppm weak acid solution as compared to the control group for any of the bacteria, except for Erysipelotrichaceae and Firmicutes, where the ratio of T-RFLP peaks was higher in the 5 ppm group for Erysipelotrichaceae and in the 10 ppm group for Firmicutes than that in the control group (P<0.01). The results suggest that the weak acid hypochlorous solution could not eradicate P. aeruginosa completely from rats. The solution was effective in preventing infection without affecting serum biochemical variables; however, some of bacterial microbiota may have changed due to administration of the solution.

SUBMITTER: Goto K

PROVIDER: S-EPMC4427734 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Effect of hypochlorous acid solution on the eradication and prevention of Pseudomonas aeruginosa infection, serum biochemical variables, and cecum microbiota in rats.

Goto Kazuo K Kuwayama Eri E Nozu Ryoko R Ueno Masami M Hayashimoto Nobuhito N

Experimental animals 20150122 2

In this study, hypochlorous acid solution, a weak acid, provided as drinking water to rats, was evaluated for its ability to eradicate and prevent Pseudomonas aeruginosa infection, while monitoring its simultaneous effect on serum biochemical variables and microbiota in the rat cecum. The results suggest that the solution could not eliminate the bacteria in the experimentally infected rats; however, the administration of a 10-parts-per-million (ppm) hypochlorous acid solution as drinking water w ...[more]

PMID: 25736708

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Project description:Pseudomonas aeruginosa is a significant nosocomial pathogen and is associated with lung infections in cystic fibrosis (CF). Once established, P. aeruginosa infections persist and are rarely eradicated despite host immune cells producing antimicrobial oxidants, including hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). There is limited knowledge as to how P. aeruginosa senses, responds to, and protects itself against HOCl and HOSCN and the contribution of such responses to its success as a CF pathogen. To investigate the P. aeruginosa response to these oxidants, we screened 707 transposon mutants, with mutations in regulatory genes, for altered growth following HOCl exposure. We identified regulators of antibiotic resistance, methionine biosynthesis, catabolite repression, and PA14_07340, the homologue of the Escherichia coli HOCl-sensor RclR (30% identical), which are required for protection against HOCl. We have shown that RclR (PA14_07340) protects specifically against HOCl and HOSCN stress and responds to both oxidants by upregulating the expression of a putative peroxiredoxin, rclX (PA14_07355). Transcriptional analysis revealed that while there was specificity in the response to HOCl (231 genes upregulated) and HOSCN (105 genes upregulated), there was considerable overlap, with 74 genes upregulated by both oxidants. These included genes encoding the type 3 secretion system, sulfur and taurine transport, and the MexEF-OprN efflux pump. RclR coordinates part of the response to both oxidants, including upregulation of pyocyanin biosynthesis genes, and, in the presence of HOSCN, downregulation of chaperone genes. These data indicate that the P. aeruginosa response to HOCl and HOSCN is multifaceted, with RclR playing an essential role.IMPORTANCE The bacterial pathogen Pseudomonas aeruginosa causes devastating infections in immunocompromised hosts, including chronic lung infections in cystic fibrosis patients. To combat infection, the host's immune system produces the antimicrobial oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). Little is known about how P. aeruginosa responds to and survives attack from these oxidants. To address this, we carried out two approaches: a mutant screen and transcriptional study. We identified the P. aeruginosa transcriptional regulator, RclR, which responds specifically to HOCl and HOSCN stress and is essential for protection against both oxidants. We uncovered a link between the P. aeruginosa transcriptional response to these oxidants and physiological processes associated with pathogenicity, including antibiotic resistance and the type 3 secretion system.

Project description:Purpose: The aim of this study was to determine the transcriptional response of P. aeruginosa PA14 to HOCl and HOSCN stress, and determine genes dependent on RclR (PA14_07340) regulation. Methods: PA14 WT and ∆rclR exponential phase cultures were exposed to sub-lethal amounts of HOCl or HOSCN (2.2 or 0.8 mM, respectively), or untreated, and after 20 minutes of exposure, RNA was extracted and gene expression analysed by RNA-seq. Reads Per Kilobase per Million mapped reads (RPKM) were determined and the log2 fold change of the RPKM values of treated WT compared to untreated WT, or treated WT compared to treated ∆rclR was calculated. Genes with a log2 fold change of >1.5 were considered upregulated and genes with a log2 fold change of <-1.5 were considered downregulated. Results: In the WT strain, HOCl exposure resulted in upregulation of 231 genes and downregulation of 20 genes, and HOSCN exposure caused upregulation of 105 genes and downregulation of 16 genes. There was considerable overlap in the transcriptional response to HOCl and HOSCN, with 74 genes being induced in response to both oxidants. Genes upregulated by HOCl and HOSCN included those involved in sulphur and taurine transport, those encoding the type 3 secretion system, the MexEF-OprN drug efflux pump, and the putative peroxiredoxin RclX (PA14_07355). Comparison of the treated WT and treated ∆rclR strains revealed that in the presence of HOCl RclR upregulated 42 genes and downregulated 7 genes, and in the presence of HOSCN upregulated 132 genes and downregulated 213 genes. In the presence of both HOCl and HOSCN, RclR was required for upregulation of rclX as well as pyocyanin biosynthesis genes. In the presence of HOSCN, RclR downregulated a large number of genes, including those encoding chaperones. Conclusions: Our data have identified that the transcriptional response of P. aeruginosa to HOCl and HOSCN is multifaceted and appears to be linked to antibiotic resistance and the virulence factors pyocyanin and type 3 secretion. Determination of the regulon of the transcriptional regulator RclR after HOCl and HOSCN exposure suggests RclR has a role in coordinating the P. aeruginosa response to these oxidants.

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Effect of hypochlorous acid solution on the eradication and prevention of Pseudomonas aeruginosa infection, serum biochemical variables, and cecum microbiota in rats.

Publications

Effect of hypochlorous acid solution on the eradication and prevention of Pseudomonas aeruginosa infection, serum biochemical variables, and cecum microbiota in rats.

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