4.6 Article

Adsorption of Phenazines Produced by Pseudomonas aeruginosa Using AST-120 Decreases Pyocyanin-Associated Cytotoxicity

Journal

ANTIBIOTICS-BASEL
Volume 10, Issue 4, Pages -

Publisher

MDPI
DOI: 10.3390/antibiotics10040434

Keywords

antimicrobial resistance (AMR); multi-drug resistance (MDR); quorum sensing; virulence; bacterial pathogenesis; molecular genetics; signal transduction; infection control

Funding

  1. Japan Society for the Promotion of Science (JSPS) [19K07533]
  2. Japan Agency for Medical Research and Development (AMED) [21fk0108604h0901]
  3. Grants-in-Aid for Scientific Research [19K07533] Funding Source: KAKEN

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AST-120 can adsorb both indole produced by Escherichia coli and phenazine compounds produced by Pseudomonas aeruginosa, supporting anti-Pseudomonas chemotherapy by suppressing associated toxicity. Additionally, it proposed a novel method to treat P. aeruginosa infection despite the presence of antibiotics like fosfomycin, colistin, and amikacin.
AST-120 (Kremezin) is used to treat progressive chronic kidney disease by adsorbing uremic toxin precursors produced by the gut microbiota, such as indole and phenols. Previously, we found that AST-120 decreased drug tolerance and virulence in Escherichia coli by adsorbing indole. Here, we show that AST-120 adsorbs phenazine compounds, such as pyocyanin, produced by Pseudomonas aeruginosa including multidrug-resistant P. aeruginosa strains, and suppresses pyocyanin-associated toxicity in A-549 (alveolar adenocarcinoma) and Caco-2 (colon adenocarcinoma) cells. Addition of fosfomycin, colistin and amikacin, which are often used to treat P. aeruginosa, inhibited the bacterial growth, regardless of the presence or absence of AST-120. These results suggest a further benefit of AST-120 that supports anti-Pseudomonas chemotherapy in addition to that of E. coli and propose a novel method to treat P. aeruginosa infection.

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