The Small Molecule DAM Inhibitor, Pyrimidinedione, Disrupts Streptococcus pneumoniae Biofilm Growth In Vitro

Yadav, Mukesh; Go, Yoon Young; Chae, Sung Won; Song, Jae Jun

doi:10.1371/journal.pone.0139238

Cited by 22 publications

(16 citation statements)

References 71 publications

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“…Biofilm can resist antibiotic killing without any drug resistance mechanisms. The link between the presence of persisters and biofilm formation is the subject of many studies [31, 32, 58, 59]. We propose that the roles of the srRNAs in persistence are associated with their biofilm formation capability, based on our findings.…”

Section: Discussionsupporting

confidence: 64%

Identification of small regulatory RNAs involved in persister formation

Zhang

Liu

et al. 2018

Preprint

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12Small regulatory RNA (srRNA) is widely distributed in three kingdoms of life and 13 fulfills functions in many aspects of cellular life, but their role in bacterial persistence 14 remains unknown. In this study, we comprehensively interrogated the expression 15 levels of the known srRNAs on three critical time points, stage 1 (S1) where no 16 persisters are formed, stage 2 (S2) where persisters are beginning to appear, and stage 17 3 (S3) where persister numbers increase significantly. Three upregulated srRNAs 18 (OmrB, an outer member associated srRNA; RdlB, a swarming motility and curli 19 expression regulator; McaS, a flagellar motility and biofilm formation regulator) 20 overlapping in S2/S1and S3/S1, together with the other four upregulated srRNAs 21 (MicF, a ribosome binding inhibitor; MicL, an outer membrane associated srRNA; 22 RybB, a cell envelope stress regulator; RydB, regulator of a global regulator RpoS) in 23 S2/S1 are of special interest. By constructing deletion mutants and overexpression 24 strains in uropathogenic E. coli strain UTI89, we tested their persister-formation 25 capabilities in log phase and stationary phase cultures exposed to antibiotics 26 (gentamicin, cefotaxime and levofloxacin) and stresses (heat, hyperosmosis, H2O2, 27 and acid). The results of the deletion mutant studies showed that all the seven 28 identified sRNAs have varying effects on persister formation with different antibiotics 29 or stresses. Moreover, we found all the deletion mutants of these srRNAs have 30 reduced biofilm formation. Additionally, except the McaS and the RydB 31 overexpression strains, all of the srRNAs overexpression strains demonstrated 32increased persister-formation in antibiotic and stress persister assays, confirming the 33 role of these srRNAs in persistence. Together, we identified seven srRNAs (OmrB, 34 RdlB, McaS, MicF, MicL, RybB, and RydB) that are involved in type II persister 35 formation for the first time. These findings provide convincing evidence for a new 36 level of rapid persistence regulation via srRNA and furnish novel therapeutic targets 37 for intervention. 38 biofilm 40 Introduction 41 Persisters have drawn wide attention since they can be identified in almost every 42 bacterial species, even in fungi and eukaryotic human cancer cells [1][2][3][4][5]. They refer to 43 a small subpopulation of dormant cells that can survive lethal antibiotics or stresses 44 and regain susceptibilities when regrowing in fresh medium [6][7][8]. Persisters account 45 for the recalcitrance of treatment of many persistent bacterial infections and can 46 facilitate the emergence of antibiotic resistant bacteria [7][8][9][10][11]. Consequently, persisters 47 pose great challenges for effective treatment of many bacterial infections 48 Persisters are divided into, type I and type II persisters [12]. Type I persisters stem 49 from the stationary phase, while type II persisters are induced by triggering 50 environmental signals as the cultures grow older from log phase to...

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Section: Discussionsupporting

confidence: 64%

Identification of small regulatory RNAs involved in persister formation

Zhang

Liu

et al. 2018

Preprint

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“…GC-MS analysis showed that the major components of T. daenensis were phenolic compounds, such as carvacrol and terpinene compounds, such as γ-terpinene and α-terpinene. Previous studies reported that EOs containing phenolic and terpinene compounds have a strong antimicrobial activity [29]. EOs of S. hortensis and O. vulgare had good antibacterial activities against S. pneumoniae.…”

Section: Discussionmentioning

confidence: 96%

Streptococcus pneumoniae quorum sensing and biofilm formation are affected by Thymus daenensis, Satureja hortensis, and Origanum vulgare essential oils

Sharifi

Ahmadi

Mohammadzadeh

2018

AMicr

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The aim of this study was to investigate the effect of Thymus daenensis L., Satureja hortensis L., and Origanum vulgare L. essential oils (EOs) on the planktonic growth, biofilm formation, quorum sensing (QS), and competence system (CS) of Streptococcus pneumoniae. The anti-biofilm activity of EOs was determined by Microtiter-Plate Test (MtP) and scanning electron microscope (SEM). The QS and CS inhibitory activities were determined on the pre-grown biofilm by gene expression analysis using quantitative real-time RT-PCR. Using gas chromatography-mass spectrometry analysis, the major components of the tested EOs were detected. The MtP and SEM detected a significant inhibitory effect of the three EOs on biofilm formation at sub-minimum inhibitory concentrations (MICs). The most anti-biofilm activity was seen for T. daenensis. LuxS and pfs genes (genes involved in QS) downregulated the following treatment with MIC/2 of Thymus and Satureja EOs. Thymol, carvacrol, p-cymene, pulegone, and 1,8-cineole were the major components of the tested EOs. The used EOs seem to be good candidates for preventing biofilm formation and subsequent colonization of S. pneumoniae. This study introduced T. daenensis and S. hortensis as new anti-biofilm and QS inhibitor agents with a natural origin.

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“…The effect eugenol may be related to the ability to prevent biofilm organization and to disaggregate micro colonies, as demonstrated by Yadav et al (2015) against Streptococcus pneumoniae.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Streptococcus mutans (ATCC 25175) biofilm formation on eugenol-impregnated surgical sutures

Victor¹,

Elaine²,

Maria³

et al. 2019

Afr. J. Microbiol. Res.

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The use of bioactive compounds as anti-infective coating on biomaterial surfaces has been studied as a tool against microbial adhesion and the establishment of biofilms. The objective of this work was to evaluate the antibacterial activity of eugenol, specifically the ability to interact with cotton suture threads for preventing adhesion and biofilm formation of Streptococcus mutans (ATCC 25175). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of eugenol were determined according to Clinical and Laboratory Standards Institute (CLSI), which showed respective concentration values of 250 and 1000 μg/ml. In addition, eugenol displayed marked activity against to biofilm formation in 96-well polystyrene plates against several strains from the Streptococcus genus, even at lower than bacteriostatic concentrations between 15 to 250 μg/ml. Moreover, eugenol formed an effective covering on cotton-suture surfaces that inhibited cell adhesion, which decreased the S. mutans (ATCC 25175) biofilm development, according to biomass and metabolic rate, quantified by crystal violet staining and XTT reduction, respectively. This research may help to explore the eugenol molecule as an antifouling coating on surfaces, bringing a new perspective to the prevention of infections associated with biomaterials.

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The Small Molecule DAM Inhibitor, Pyrimidinedione, Disrupts Streptococcus pneumoniae Biofilm Growth In Vitro

Cited by 22 publications

References 71 publications

Identification of small regulatory RNAs involved in persister formation

Identification of small regulatory RNAs involved in persister formation

Streptococcus pneumoniae quorum sensing and biofilm formation are affected by Thymus daenensis, Satureja hortensis, and Origanum vulgare essential oils

Inhibition of Streptococcus mutans (ATCC 25175) biofilm formation on eugenol-impregnated surgical sutures

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