Characterization of Distinct Biofilm Cell Subpopulations and Implications in Quorum Sensing and Antibiotic Resistance

Dodson, Taylor A.; Carlson, Eric A.; Wamer, Nathan C.; Morse, Chase N.; Gadient, Jennifer; Prestwich, Erin G.

doi:10.1128/mbio.00191-22

Cited by 8 publications

(8 citation statements)

References 70 publications

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“…Free-swimming cells transition to biofilm communities that promote cellular cooperativity and resistance to stressors and antibiotics. Biofilms are the first barrier to antimicrobial drugs entering cells and are one of the main causes of pathogenetic microbial drug resistance ( 22 ). After a C. violaceum biofilm forms, drug resistance is unavoidable ( 23 ).…”

Section: Resultsmentioning

confidence: 99%

Combination of 2- tert -Butyl-1,4-Benzoquinone (TBQ) and ZnO Nanoparticles, a New Strategy To Inhibit Biofilm Formation and Virulence Factors of Chromobacterium violaceum

Liu

Chang

et al. 2023

mSphere

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The combination of ZnO-NPs and TBQ (ZnO-TBQ) can compete with the inducer N -decanoyl-homoserine lactone (C 10 -HSL) by binding to CviR and downregulate genes related to the CviI/CviR system to interrupt the QS system of C. violaceum ATCC 12472. The downstream genes responding to cviR were also downregulated so that virulence factors and biofilm formation were inhibited.

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Section: Resultsmentioning

confidence: 99%

Combination of 2- tert -Butyl-1,4-Benzoquinone (TBQ) and ZnO Nanoparticles, a New Strategy To Inhibit Biofilm Formation and Virulence Factors of Chromobacterium violaceum

Liu

Chang

et al. 2023

mSphere

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“…Free-swimming cells transition to biofilm communities that promote cellular cooperativity and resistance to stressors and anti-bacterial drugs. Biofilms are the first barrier to antimicrobial drugs entering cells and are one of the main causes of pathogenetic microbial drug resistance (Dodson et al 2022). After a S. marcescens biofilm forms, drug resistance is unavoidable (Liu et al 2020).…”

Section: Discussionmentioning

confidence: 99%

Synthesized 3-(2-isocyano-6-methylbenzyl)-1H-indole Enhanced Susceptibility of Serratia marcescens to Kanamycinby Occluding Quorum Sensing

Yang

Wang

Tang

et al. 2023

Preprint

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Quorum sensing (QS) inhibition is recognized as a novel drug target for infections caused by drug-resistant pathogens and is an attractive strategy for the development of antipathogenic agents. Herein, we designed and synthesized three parts of3-(2-isocyanobenzyl)-1H-indole derivatives and evaluated their activity as novel quorum sensing inhibitors (QSIs). We found that 3-(2-isocyanobenzyl)-1H-indole derivatives showed promising QS inhibitory activity in the minimum inhibitory concentrations (MICs), biofilm and prodigiosin inhibition assays in Serratia marcescens. In particular, 3-(2-isocyano-6-methylbenzyl)-1H-indole(IMBI, 32) was the best candidate by biofilm and prodigiosin inhibition assays screening strategies. Further studies demonstrated, exposureIMBI (1.56 μg/mL, 1/8MICs) to S. marcescens NJ01 significantly inhibited the formation of biofilms by 42%. The IMBI treatment (1.56 μg/mL) on S. marcescens NJ01 notably enhanced the susceptibility of the formed biofilms, destroying the architecture of biofilms up to 40% as evidenced by scanning electron microscopy (SEM) and confocal laser scanning microscope (CLSM). For interference of virulence factors in S. marcescens NJ01, IMBI (3.12 μg/mL, 1/4MICs) inhibited the activity of protease, and extracellular polysaccharides (EPS)by 17% and 51% respectively, which were higher than that of the positive control vanillic acid (VAN). Furthermore, IMBI downregulated the expressions of QS- and biofilm-related genes bsmA,pigP, flhC, rssB, rsmA, and fimC by 0.13-fold to 1.46-fold. To confirm these findings, molecular docking was performed, which indicated that the binding of IMBI to SmaR, RhlI, RhlR, LasR, and CviR could antagonize the expression of QS-linked traits. In addition, molecular dynamic simulations (MD) and energy calculations indicated that the binding of receptors with IMBI was extremely stable. Most importantly, the biofilms of S. marcescens NJ01 were markedly reduced by 50% under IMBI (0.39 μg/mL, 1/32MICs)combining with 0.15 μg/mL kalamycin (KAN). In conclusion, this study highlights the potency of IMBI in inhibiting the virulence factors against S. marcescens. IMBI could be developed as an effective QS inhibitor and anti-biofilm agent to restore or improve drug sensitivity for drug-resistant pathogens.

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“…The dispersed bacteria and biofilm were separated by centrifuging at 8500 g . The supernatant was diluted and plated on LB agar plates to conduct cfu counting …”

Section: Methodsmentioning

confidence: 99%

“…The supernatant was diluted and plated on LB agar plates to conduct cfu counting. 53 Checkerboard Assays. A single colony of the PAO1-ΔwspF strain was cultured in LB medium with shaking at 37 °C overnight.…”

Section: ■ Conclusionmentioning

confidence: 99%

Cyclic Diguanylate G-Quadruplex Inducer-Nitric Oxide Donor Conjugate as a Bifunctional Antibiofilm Agent and Antibacterial Synergist against Pseudomonas aeruginosa with a Hyperbiofilm Phenotype

Lin,

Lu,

Huang

et al. 2023

J. Med. Chem.

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Antibiotic resistance caused by biofilm formation is a clinical challenge. Nitric oxide (NO) can effectively disperse a mature biofilm and can also synergistically influence the level of cyclic diguanylate (c-di-GMP), a universal secondary messenger that plays an important role in biofilm formation in bacteria. Based on our previous finding that c-di-GMP G-quadruplex inducers are effective biofilm formation inhibitors, we designed and synthesized a c-di-GMP G-quadruplex inducer-NO donor conjugate (A11@ NO) as a bifunctional antibiofilm agent after obtaining the c-di-GMP G-quadruplex inducer (A11), which has an amino group capable of binding to a nitroso group (NO donor). The conjugate A11@NO showed better biofilm inhibition efficiency than A11, and it can also eradicate mature biofilm. Additionally, it exhibited good antimicrobial synergism against Pseudomonas aeruginosa and helped elevate the bactericidal efficiency of tobramycin against biofilm-formed bacteria. In combination with tobramycin, A11@NO also improved the survival rate of Caenorhabditis elegans in a hyperbiofilm environment.

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Characterization of Distinct Biofilm Cell Subpopulations and Implications in Quorum Sensing and Antibiotic Resistance

Cited by 8 publications

References 70 publications

Combination of 2- tert -Butyl-1,4-Benzoquinone (TBQ) and ZnO Nanoparticles, a New Strategy To Inhibit Biofilm Formation and Virulence Factors of Chromobacterium violaceum

Combination of 2- tert -Butyl-1,4-Benzoquinone (TBQ) and ZnO Nanoparticles, a New Strategy To Inhibit Biofilm Formation and Virulence Factors of Chromobacterium violaceum

Synthesized 3-(2-isocyano-6-methylbenzyl)-1H-indole Enhanced Susceptibility of Serratia marcescens to Kanamycinby Occluding Quorum Sensing

Cyclic Diguanylate G-Quadruplex Inducer-Nitric Oxide Donor Conjugate as a Bifunctional Antibiofilm Agent and Antibacterial Synergist against Pseudomonas aeruginosa with a Hyperbiofilm Phenotype

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