Date of Award

8-2014

Degree Name

Master of Science (MS)

Department

Biomedical and Chemical Engineering

Advisor(s)

Dacheng Ren

Keywords

Antibiotic tolerance, Biofilm, Persister cells, Quorum sensing

Subject Categories

Biology | Cell and Developmental Biology

Abstract

Bacterial cells often form sessile biofilms that are up to 1,000 times more resistant to antimicrobial agents than free-living cells. Meanwhile, bacteria produce a small subpopulation of slow-growing or non-growing persister cells that exhibit high tolerance to antibiotics. Both biofilms and persister cells play important roles in the recalcitrance of chronic infections. Recent studies have shown that bacterial cell-to-cell communication, named quorum sensing (QS), is involved in the biofilm and persister formation.

In this study, we investigated the effects of quorum sensing signals N-(3-oxododecanoyl)-homoserine lactone (3-oxo-C12-HSL) and N-butyryl homoserine lactone (C4-HSL) on isolated Pseudomonas aeruginosa PAO1 and PDO300 persister cells. Interestingly, 3-oxo-C12-HSL was found to increase antibiotic susceptibility of isolated P. aeruginosa PAO1 and PDO300 persister cells to ciprofloxacin in a dose-dependent manner, although such synergistic effect was not observed with ofloxacin, tobramycin, tetracycline, carbenicillin, and gentamicin. In contrast, C4-HSL did not affect the susceptibility of P. aeruginosa PAO1 and PDO300 persister cells to ciprofloxacin.

Additionally, we engineered polydimethylsiloxane (PDMS) surfaces by supplementing with (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-25(H)-one (BF8) to reduce P. aeruginosa PAO1 biofilm formation and biofilm-associated persister cells. Compared with the PDMS surface without BF8, P. aeruginosa PAO1 biofilm formation and biofilm-associated persister cells were significantly reduced on the PDMS surfaces containing BF8. For example, after 24 h, the number of biofilm cells and biofilm-associated persisters was inhibited by 98% 0.4% and 99% 0.5% on the PDMS surface containing 1800 μg/mL BF8, respectively. These results further support that bacterial cell-to-cell signaling is a possible target for controlling biofilm formation and persistence.

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Open Access

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