title: Human Granulocyte Macrophage Colony-Stimulating Factor Enhances Antibiotic Susceptibility of Pseudomonas aeruginosa Persister Cells.
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.
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA.|Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Geetika S
authors.initials: GS
authors.lastname: Choudhary
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA.|Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA.|Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA.|Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA.|Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Bader
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA.|Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA.|Department of Civil and Environmental Engineering, Syracuse University, Syracuse, NY 13244, USA.|Department of Biology, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Dacheng
authors.initials: D
authors.lastname: Ren
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D010933:Plankton / Q000187:drug effects; D011133:Polysaccharide-Lyases / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011133:Polysaccharide-Lyases; C016158:poly(beta-D-mannuronate) lyase