Role of psl Genes in Antibiotic Tolerance of Adherent Pseudomonas aeruginosa

Bacteria attached to a surface are generally more tolerant to antibiotics than their planktonic counterparts, even without the formation of a biofilm. The mechanism of antibiotic tolerance in biofilm communities is multifactorial, and the genetic background underlying this antibiotic tolerance has n...

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Veröffentlicht in:Antimicrobial agents and chemotherapy 2017-07, Vol.61 (7)
Hauptverfasser: Murakami, Keiji, Ono, Tsuneko, Viducic, Darija, Somiya, Yoko, Kariyama, Reiko, Hori, Kenji, Amoh, Takashi, Hirota, Katsuhiko, Kumon, Hiromi, Parsek, Matthew R, Miyake, Yoichiro
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Sprache:eng
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Zusammenfassung:Bacteria attached to a surface are generally more tolerant to antibiotics than their planktonic counterparts, even without the formation of a biofilm. The mechanism of antibiotic tolerance in biofilm communities is multifactorial, and the genetic background underlying this antibiotic tolerance has not yet been fully elucidated. Using transposon mutagenesis, we isolated a mutant with reduced tolerance to biapenem (relative to that of the wild type) from adherent cells. Sequencing analysis revealed a mutation in the gene, which is part of the polysaccharide biosynthesis operon. The PAO1Δ mutant demonstrated a 100-fold-lower survival rate during the exposure of planktonic and biofilm cells to biapenem; a similar phenotype was observed in a mouse infection model and in clinical strains. Transcriptional analysis of adherent cells revealed increased expression of both and , which are directly regulated by bis-(3',5')-cyclic dimeric GMP (c-di-GMP). Inactivation of resulted in significantly increased tolerance to biapenem due to increased production of c-di-GMP. The loss of in the Δ mutant background abolished the biapenem-tolerant phenotype of the Δ mutant, underscoring the importance of in biapenem tolerance. Overexpression of PA2133, which can catalyze the degradation of c-di-GMP, led to a significant reduction in biapenem tolerance in adherent cells, indicating that c-di-GMP is essential in mediating the tolerance effect. The effect of on antibiotic tolerance was evident, with 50- and 200-fold-lower survival in the presence of ofloxacin and tobramycin, respectively. We speculate that the genes, which are activated by surface adherence through elevated intracellular c-di-GMP levels, confer tolerance to antimicrobials.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.02587-16