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Human Granulocyte Macrophage Colony-Stimulating Factor Enhances Antibiotic Susceptibility of Pseudomonas aeruginosa Persister Cells.

Choudhary GS, Yao X, Wang J, Peng B, Bader RA, Ren D - Sci Rep (2015)

Bottom Line: The DNA microarray and qPCR results indicated that GM-CSF induced the genes for flagellar motility and pyocin production in the persister cells, but not the normal cells of P. aeruginosa PAO1.Consistently, the supernatants from GM-CSF treated P. aeruginosa PAO1 persister cell suspensions were found cidal to the pyocin sensitive strain P. aeruginosa PAK.Collectively, these findings suggest that host immune factors and bacterial persisters may directly interact, leading to enhanced susceptibility of persister cells to antibiotics.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA.

ABSTRACT
Bacterial persister cells are highly tolerant to antibiotics and cause chronic infections. However, little is known about the interaction between host immune systems with this subpopulation of metabolically inactive cells, and direct effects of host immune factors (in the absence of immune cells) on persister cells have not been studied. Here we report that human granulocyte macrophage-colony stimulating factor (GM-CSF) can sensitize the persister cells of Pseudomonas aeruginosa PAO1 and PDO300 to multiple antibiotics including ciprofloxacin, tobramycin, tetracycline, and gentamicin. GM-CSF also sensitized the biofilm cells of P. aeruginosa PAO1 and PDO300 to tobramycin in the presence of biofilm matrix degrading enzymes. The DNA microarray and qPCR results indicated that GM-CSF induced the genes for flagellar motility and pyocin production in the persister cells, but not the normal cells of P. aeruginosa PAO1. Consistently, the supernatants from GM-CSF treated P. aeruginosa PAO1 persister cell suspensions were found cidal to the pyocin sensitive strain P. aeruginosa PAK. Collectively, these findings suggest that host immune factors and bacterial persisters may directly interact, leading to enhanced susceptibility of persister cells to antibiotics.

No MeSH data available.


Related in: MedlinePlus

Effect of 0.17 pM GM-CSF on gene expression in P. aeruginosa PAO1.(a) Number and categories of genes that were consistently induced or repressed in two biological replicates of P. aeruginosa PAO1 persister cells. (b) Number and categories of genes that were consistently induced or repressed in two biological replicates of P. aeruginosa PAO1 normal cells.
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f6: Effect of 0.17 pM GM-CSF on gene expression in P. aeruginosa PAO1.(a) Number and categories of genes that were consistently induced or repressed in two biological replicates of P. aeruginosa PAO1 persister cells. (b) Number and categories of genes that were consistently induced or repressed in two biological replicates of P. aeruginosa PAO1 normal cells.

Mentions: To better understand GM-CSF induced sensitization of persisters to antibiotics, DNA microarrays were used to compare gene expression profiles of P. aeruginosa PAO1 persister cells with and without 1 h treatment with 0.17 pM GM-CSF. The results show that a total of 89 genes were induced and 149 genes were repressed by GM-CSF more than 1.5-fold (linear ratio) in both biological replicates (Fig. 6a). The induced genes include 34 genes coding for hypothetical proteins, 19 bacteriophage-like (pyocin) genes, 10 chemotaxis genes, 8 motility genes, and 18 genes with other functions (Fig. 6a). The repressed genes include 61 genes coding for hypothetical proteins, 16 genes related to the transport of small molecules, and 12 genes encoding transcriptional regulators (Fig. 6a). Table 2 shows the expression fold change of some representative genes based on the DNA microarray results of two biological replicates.


Human Granulocyte Macrophage Colony-Stimulating Factor Enhances Antibiotic Susceptibility of Pseudomonas aeruginosa Persister Cells.

Choudhary GS, Yao X, Wang J, Peng B, Bader RA, Ren D - Sci Rep (2015)

Effect of 0.17 pM GM-CSF on gene expression in P. aeruginosa PAO1.(a) Number and categories of genes that were consistently induced or repressed in two biological replicates of P. aeruginosa PAO1 persister cells. (b) Number and categories of genes that were consistently induced or repressed in two biological replicates of P. aeruginosa PAO1 normal cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663479&req=5

f6: Effect of 0.17 pM GM-CSF on gene expression in P. aeruginosa PAO1.(a) Number and categories of genes that were consistently induced or repressed in two biological replicates of P. aeruginosa PAO1 persister cells. (b) Number and categories of genes that were consistently induced or repressed in two biological replicates of P. aeruginosa PAO1 normal cells.
Mentions: To better understand GM-CSF induced sensitization of persisters to antibiotics, DNA microarrays were used to compare gene expression profiles of P. aeruginosa PAO1 persister cells with and without 1 h treatment with 0.17 pM GM-CSF. The results show that a total of 89 genes were induced and 149 genes were repressed by GM-CSF more than 1.5-fold (linear ratio) in both biological replicates (Fig. 6a). The induced genes include 34 genes coding for hypothetical proteins, 19 bacteriophage-like (pyocin) genes, 10 chemotaxis genes, 8 motility genes, and 18 genes with other functions (Fig. 6a). The repressed genes include 61 genes coding for hypothetical proteins, 16 genes related to the transport of small molecules, and 12 genes encoding transcriptional regulators (Fig. 6a). Table 2 shows the expression fold change of some representative genes based on the DNA microarray results of two biological replicates.

Bottom Line: The DNA microarray and qPCR results indicated that GM-CSF induced the genes for flagellar motility and pyocin production in the persister cells, but not the normal cells of P. aeruginosa PAO1.Consistently, the supernatants from GM-CSF treated P. aeruginosa PAO1 persister cell suspensions were found cidal to the pyocin sensitive strain P. aeruginosa PAK.Collectively, these findings suggest that host immune factors and bacterial persisters may directly interact, leading to enhanced susceptibility of persister cells to antibiotics.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA.

ABSTRACT
Bacterial persister cells are highly tolerant to antibiotics and cause chronic infections. However, little is known about the interaction between host immune systems with this subpopulation of metabolically inactive cells, and direct effects of host immune factors (in the absence of immune cells) on persister cells have not been studied. Here we report that human granulocyte macrophage-colony stimulating factor (GM-CSF) can sensitize the persister cells of Pseudomonas aeruginosa PAO1 and PDO300 to multiple antibiotics including ciprofloxacin, tobramycin, tetracycline, and gentamicin. GM-CSF also sensitized the biofilm cells of P. aeruginosa PAO1 and PDO300 to tobramycin in the presence of biofilm matrix degrading enzymes. The DNA microarray and qPCR results indicated that GM-CSF induced the genes for flagellar motility and pyocin production in the persister cells, but not the normal cells of P. aeruginosa PAO1. Consistently, the supernatants from GM-CSF treated P. aeruginosa PAO1 persister cell suspensions were found cidal to the pyocin sensitive strain P. aeruginosa PAK. Collectively, these findings suggest that host immune factors and bacterial persisters may directly interact, leading to enhanced susceptibility of persister cells to antibiotics.

No MeSH data available.


Related in: MedlinePlus