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All Journal Eureka Herba Indonesia Crown: Journal of Dentistry and Health Research
Danniel Hilman Maulana
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Dentistry Health Professions Medicine & Pharmacology Neuroscience Public Health

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CRISPRi-Mediated Repression of gtfB Attenuates Streptococcus mutans Virulence and Promotes Ecological Homeostasis in a Preclinical Cariogenic Biofilm Model Khairiel Anwar; Maria Rodriguez; Sony Sanjaya; Danniel Hilman Maulana; Karina Chandra; Isadora Selestine
Crown: Journal of Dentistry and Health Research Vol. 3 No. 1 (2025): Crown: Journal of Dentistry and Health Research
Publisher : Phlox Institute: Indonesian Medical Research Organization

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59345/crown.v3i1.234

Abstract

Introduction: Streptococcus mutans is a primary etiological agent of dental caries, largely due to its capacity to form robust, acidogenic biofilms. This virulence is critically dependent on glucosyltransferases, particularly GtfB, which synthesizes the adhesive extracellular glucan matrix. Conventional antimicrobial strategies often lack specificity, leading to oral dysbiosis. This study aimed to develop and evaluate a highly targeted CRISPR interference (CRISPRi) system to silence the gtfB gene in S. mutans, thereby inhibiting its cariogenic potential without adversely affecting the viability of key oral commensal species. Methods: A CRISPRi system, comprising a nuclease-deactivated Cas9 (dCas9) and a single guide RNA (sgRNA) targeting the gtfB promoter, was engineered into S. mutans UA159. The efficacy of gtfB silencing was quantified via qRT-PCR. The consequential effects on bacterial growth kinetics, insoluble glucan synthesis, and single-species biofilm formation were assessed using spectrophotometry, anthrone assays, crystal violet staining, and confocal laser scanning microscopy (CLSM). The ecological impact was investigated in a multi-species biofilm model containing S. mutans and the commensal bacteria Streptococcus gordonii, Streptococcus oralis, and Actinomyces naeslundii, with microbial composition analyzed by species-specific qPCR. All research activities were conducted in Indonesia. Results: The CRISPRi system induced a profound and specific downregulation of gtfB mRNA expression by over 98% (p<0.001) in the engineered S. mutans strain compared to the wild-type. This silencing did not impair bacterial planktonic growth. However, it led to a significant reduction in insoluble glucan production by 85% (p<0.001) and a corresponding 79% decrease in total biofilm biomass (p<0.001). CLSM imaging confirmed the formation of structurally deficient biofilms with minimal extracellular matrix. In the multi-species model, repression of S. mutans virulence significantly altered the biofilm ecology, resulting in a 65% reduction in the proportional abundance of S. mutans and a concomitant increase in the representation of commensal species, thereby fostering a community structure more aligned with oral health. Conclusion: Targeted repression of the gtfB gene using a CRISPRi-based approach effectively 'disarms' S. mutans, neutralizing its primary cariogenic mechanism without being bactericidal. This strategy not only attenuates its virulence but also shifts the ecological balance in favor of beneficial commensal bacteria. These findings underscore the therapeutic potential of gene-targeted virulence modulation as a precise, ecologically-sound strategy for the prevention and treatment of dental caries.
Modulation of the Cognition-Sleep Nexus in Subjective Cognitive Decline: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial of a Standardized Cordyceps militaris Extract Vita Amanda; Daphne Marshall; Zahra Amir; Husin Sastranagara; Danniel Hilman Maulana; Karina Chandra; Fachrudin Sani
Eureka Herba Indonesia Vol. 6 No. 2 (2025): Eureka Herba Indonesia
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/ehi.v6i2.130

Abstract

Subjective cognitive decline (SCD) and sleep disturbance form a vicious cycle, accelerating neurodegeneration. Cordyceps militaris (CM), a traditional medicinal fungus rich in nucleosides, possesses potent neuroprotective and adenosinergic (sleep-promoting) properties. We investigated the efficacy of a standardized CM extract on this cognition-sleep nexus in adults with SCD. This 12-week, single-center, randomized, double-blind, placebo-controlled, parallel-group trial was conducted in Palembang, Indonesia. We randomized 120 adults (aged 45-65) with SCD to receive 300 mg/day of a standardized CM mycelial extract (3% cordycepin) or a matching placebo. The primary outcome was the change from baseline in the Montreal Cognitive Assessment-Indonesian (MoCA-INA) score. Key secondary outcomes (Bonferroni-corrected) were the Pittsburgh Sleep Quality Index (PSQI), Rey Auditory Verbal Learning Test (RAVLT) Delayed Recall, and polysomnography (PSG)-derived Sleep Efficiency (SE). Analyses were performed on the Intention-to-Treat (ITT) population (N=120) using a Linear Mixed-Effects Model (LMM). The LMM analysis revealed a significant group-by-time interaction for the primary outcome, MoCA-INA (Adjusted Mean Difference [AMD]: +1.95 [95% CI: 1.10, 2.80], p < 0.001). The CM group also showed significant improvements in all three key secondary outcomes: PSQI (AMD: -2.90 [95% CI: -3.81, -1.99], p < 0.001), RAVLT Delayed Recall (AMD: +2.15 [95% CI: 1.30, 3.00], p < 0.001), and Sleep Efficiency (AMD: +5.8% [95% CI: 3.1, 8.5], p < 0.001). After FDR correction, significant benefits were also seen for processing speed, %REM sleep, and serum BDNF and hs-CRP. The intervention was well-tolerated. In conclusion, twelve weeks of supplementation with a standardized C. militaris extract significantly improved cognitive function, episodic memory, and both subjective and objective sleep in adults with SCD. These benefits were associated with enhanced neuroplasticity and reduced systemic inflammation, supporting its potential as a multi-target, disease-modifying intervention for this at-risk population.
Co-Authors Daphne Marshall Fachrudin Sani Husin Sastranagara Isadora Selestine Karina Chandra Khairiel Anwar Maria Rodriguez Sony Sanjaya Vita Amanda Zahra Amir