Anti-Candida albicans biofilm effect of novel heterocyclic compounds

Kagan, Sarah; Jabbour, Adel; Sionov, Edward; Al-Quntar, Abed; Steinberg, Doron; Srebnik, Morris; Nir-Paz, Ran; Weiss, Aryeh; Polacheck, Itzhack

doi:10.1093/jac/dkt365

Cited by 35 publications

(45 citation statements)

References 51 publications

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“…In comparison to the susceptibility to fungicides of the planktonic form, the fungicide susceptibility of fungi immobilized in a biofilm is very low. This resistance is multifactorial and complex, involving (i) limited drug penetration into the biofilm due to the high density of the extracellular matrix, (ii) drug absorption or binding by the biofilm extracellular matrix, (iii) decreased growth rate, (iv) overexpression of genes involved in drug resistance, particularly those encoding efflux pumps, (v) and multidrug tolerance due to persistent cells (5,(9)(10)(11).…”

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confidence: 99%

“…Thiazolidinediones (TZDs) have been proposed as potential QS inhibitors in Vibrio harveyi (13). Several TZD derivatives have also been tested for their ability to affect C. albicans pathogenicity (9).…”

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confidence: 99%

“…In previous studies, we demonstrated a specific antibiofilm effect and molecular mechanism of action of the TZD derivative thiazolidinedione-8 (S-8) in solution against C. albicans (7,9). In addition, S-8 was tested for mammalian toxicity in female ICR mice.…”

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confidence: 99%

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Sustained Release of a Novel Anti-Quorum-Sensing Agent against Oral Fungal Biofilms

Feldman

Shenderovich

Al-Quntar

et al. 2015

Antimicrob Agents Chemother

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b Thiazolidinedione-8 (S-8) has recently been identified as a potential anti-quorum-sensing/antibiofilm agent against bacteria and fungi. Based on these results, we investigated the possibility of incorporating S-8 in a sustained-release membrane (SRM) to increase its pharmaceutical potential against Candida albicans biofilm. We demonstrated that SRM containing S-8 inhibits fungal biofilm formation in a time-dependent manner for 72 h, due to prolonged release of S-8. Moreover, the SRM effectively delivered the agent in its active form to locations outside the membrane reservoir. In addition, eradication of mature biofilm by the SRM containing S-8 was also significant. Of note, S-8-containing SRM affected the characteristics of mature C. albicans biofilm, such as thickness, exopolysaccharide (EPS) production, and morphogenesis of fungal cells. The concept of using an antibiofilm agent with no antifungal activity incorporated into a sustained-release delivery system is new in medicine and dentistry. This concept of an SRM containing a quorum-sensing quencher with an antibiofilm effect could pave the way for combating oral fungal infectious diseases.

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confidence: 99%

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confidence: 99%

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Sustained Release of a Novel Anti-Quorum-Sensing Agent against Oral Fungal Biofilms

Feldman

Shenderovich

Al-Quntar

et al. 2015

Antimicrob Agents Chemother

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“…Current research is focused on developing methods to prevent or control biofilm formation (6,7). We recently found three analogues of N-acyl homoserine lactone that participate in quorum sensing, a system of bacterial cell-to-cell communication, and inhibit Porphyromonas gingivalis biofilm formation (8).…”

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confidence: 99%

Promotion of Endodontic Lesions in Rats by a Novel Extraradicular Biofilm Model Using Obturation Materials

Kuremoto

Noiri

Ishimoto

et al. 2014

Appl Environ Microbiol

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bAlthough extraradicular biofilm formation is related to refractory periapical periodontitis, the mechanism of extraradicular biofilm development, as well as its effect on periapical lesions, is unknown. Therefore, we aimed to develop an in vivo extraradicular biofilm model in rats and to identify and quantify extraradicular biofilm-forming bacteria while investigating the effect of extraradicular biofilms on periapical lesions. Periapical lesions were induced by exposing the pulpal tissue of the mandibular first molars of male Wistar rats to their oral environment. Four weeks later, gutta-percha points were excessively inserted into the mesial root canals of the right first molars (experimental sites) but not the left first molars (control sites). After 6 and 8 weeks of pulp exposure, the presence of extraradicular biofilms was confirmed histomorphologically, and biofilm-forming bacteria were identified by using classical culture methods. The biofilms were observed in the extraradicular area of the experimental sites. Similar species were detected both inside and outside the root canals. The bacterial count, quantified by real-time PCR assays, in the extraradicular area gradually increased in the experimental sites until 20 weeks after pulp exposure. After 8 weeks of pulp exposure, the periapical lesion volume that was measured by micro-computed tomography was significantly larger in the experimental sites than in the control sites (P < 0.05 by Welch's t test). These results suggest that we developed an extraradicular biofilm model in rats and that extraradicular biofilms affect developing periapical lesions. In clinical practice, we encounter patients in whom periapical periodontitis does not heal despite a root canal treatment following general dental procedures. The etiology is considered to be the result of residual bacteria in the lateral branch of the root canal, endodontic reinfection, or both. Recent studies have shown that biofilms that form outside the apical foramen, which are termed "extraradicular biofilm," are also involved in refractory periapical periodontitis (1-4). As the bacteria in biofilms are resistant to the host's immunoreaction and to antibiotics (5), dental biofilm diseases such as caries or periodontitis have been treated by mechanical removal. However, extraradicular biofilm is impossible to remove mechanically with nonsurgical endodontic treatments. As extraradicular biofilms cannot be accessed from the root canal for mechanical removal, the only treatment methods are endodontic surgery and tooth extraction.Current research is focused on developing methods to prevent or control biofilm formation (6, 7). We recently found three analogues of N-acyl homoserine lactone that participate in quorum sensing, a system of bacterial cell-to-cell communication, and inhibit Porphyromonas gingivalis biofilm formation (8). Furthermore, azithromycin, a 15-membered macrolide antibiotic, has an antibiofilm effect on P. gingivalis (9). For clinical applicability, these in vitro effects should be exami...

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“…Bromine-containing furanones are potential inhibitors of biofilm of several pathogens [40]. Sulfur atom plays a role in biofilm inhibition [41]. Though many QS inhibitors were ascertained from various biological resources [42][43][44] this study highlighted the significance of the bacterial source especially E. durans and its possible quorum quenching mechanisms.…”

Section: Gc-ms Analysismentioning

confidence: 96%

Quorum Quenching Potentials of Probiotic Enterococcus Durans Lab38 Against Methicillin Resistant Staphylococcus Aureus

Sivakumar

Boopathi²,

Selvakumar³

2017

Asian J Pharm Clin Res

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Objective: The focus of this study was to explore the nuance strategy to combat the virulence factors of the pathogens by probiotic Enterococcus durans LAB38.Methods: Probiotic attributes was determined by bile salt tolerance (0.5%) and Artemia gnotobiotic assay. Quorum sensing (QS) inhibitory activity of the supernatant and ethyl acetate (EA) extract of LAB38 was evaluated using the indicator strains, includes Chromobacterium violaceum CV026 (miniTn5 mutant of ATCC 31532), methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA). Reporter strains, Vibrio harveyi BB170 (luxN mutant), BB886 (luxP mutant) and Escherichia coli pSB401 (pACYC184-derived) were used for bioluminescence-based target specificity analysis. Gas chromatography-mass spectrometry (GC-MS) analysis of EA extract was performed using standard protocol.Results: LAB38 has shown bile salt tolerance and positive probiotic effect toward Artemia salina. In addition, 100 µg/ml EA extract has significantly reduced the violacein production (37±1.4%) in CV026, biofilm formation in MRSA (94±0.9 %) and PA (22±0.08%). Further, 200 µg/ml of EA extract has shown inhibition against both autoinducer-1 (AI-1) and AI-2 mediated QS system. Bioluminescence inhibition is directly proportional to the time of exposure. GC-MS result revealed that bromine, sulfur containing molecule and azulene derivative were found in the EA extract. Conclusion:This is the first report on probiotic E. durans for quorum quenching activity. Hence, the bacterium could be used for future therapeutics application.

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Anti-Candida albicans biofilm effect of novel heterocyclic compounds

Abstract: We developed novel anti-biofilm agents that both inhibited and destroyed C. albicans biofilm. With some further development, these agents might be suitable for therapeutic purposes.

Cited by 35 publications

References 51 publications

Sustained Release of a Novel Anti-Quorum-Sensing Agent against Oral Fungal Biofilms

Sustained Release of a Novel Anti-Quorum-Sensing Agent against Oral Fungal Biofilms

Promotion of Endodontic Lesions in Rats by a Novel Extraradicular Biofilm Model Using Obturation Materials

Quorum Quenching Potentials of Probiotic Enterococcus Durans Lab38 Against Methicillin Resistant Staphylococcus Aureus

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