Synbiotic Musa acuminata skin extract and Streptococcus salivarius K12 inhibit candida species biofilm formation.

This study aimed to determine the effect of synbiotic Musa acuminata skin extract (MASE) and Streptococcus salivarius K12 (K12) on Candida species biofilm formation. Liquid chromatography quadrupole time-of-flight (LC-Q-TOF-MS) was conducted to characterize MASE. To determine the effect of synbiotic on Candida biofilm, 200 µL of RPMI-1640 containing Candida, K12, and MASE were pipetted into the same well and incubated at 37 °C for 72 h. A similar protocol was repeated with K12 or MASE to determine the probiotic and prebiotic effects, respectively. Dimorphism, biofilm biomass, and Candida total cell count (TCC) were determined. A total of 60 compounds were detected in MASE. C. albicans (ALT5) and Candida lusitaniae exhibited the highest reduction in biofilm biomass when co-cultured with prebiotic (77.70 ± 7.67%) and synbiotic (97.73 ± 0.28%), respectively. All Candida spp. had decreased TCC and hyphae when co-cultured with synbiotic. In conclusion, MASE and K12 inhibit Candida biofilm formation.

Viral, bacterial, and fungal infections of the oral mucosa: Types, incidence, predisposing factors, diagnostic algorithms, and management.

For millions of years, microbiota residing within us, including those in the oral cavity, coexisted in a harmonious symbiotic fashion that provided a quintessential foundation for human health. It is now clear that disruption of such a healthy relationship leading to microbial dysbiosis causes a wide array of infections, ranging from localized, mild, superficial infections to deep, disseminated life-threatening diseases. With recent advances in research, diagnostics, and improved surveillance we are witnessing an array of emerging and re-emerging oral infections and orofacial manifestations of systemic infections. Orofacial infections may cause significant discomfort to the patients and unnecessary economic burden. Thus, the early recognition of such infections is paramount for holistic patient management, and oral clinicians have a critical role in recognizing, diagnosing, managing, and preventing either new or old orofacial infections. This paper aims to provide an update on current understanding of well-established and emerging viral, bacterial, and fungal infections manifesting in the human oral cavity.

Inhibitory effects of fruit berry extracts on Streptococcus mutans biofilms.

Dark-colored fruit berries are a rich source of polyphenols that could provide innovative bioactive molecules as natural weapons against dental caries. High-quality extracts of cranberry, blueberry, and strawberry, and a combination of the three berry extracts (Orophenol), were used to treat 24-h-old Streptococcus mutans biofilms. The grown biofilms were treated with the berry extracts at concentrations ranging from 62.5 to 500 µg ml-1 . Treated biofilms were assessed for metabolic activity, acidogenicity, biovolumes, structural organization, and bacterial viability. The biofilms treated with the cranberry and Orophenol extracts exhibited the most significant reductions in metabolic activity, acid production, and bacterial/exopolysaccharide (EPS) biovolumes, while their structural architecture appeared less compact than the control-treated biofilms. The blueberry extract produced significant reductions in metabolic activity and acidogenicity only at the highest concentration tested, without significantly affecting bacterial/EPS biovolumes or biofilm architecture. Strawberry extracts had no significant effects on S. mutans biofilms. None of the berry extracts were bactericidal for S. mutans. The results indicate that cranberry extract was the most effective extract in disrupting S. mutans virulence properties without significantly affecting bacterial viability. This suggests a potential ecological role for cranberry phenols as non-bactericidal agents capable of modulating pathogenicity of cariogenic biofilms.

Casein Phosphopeptide-Amorphous Calcium Phosphate Attenuates Virulence and Modulates Microbial Ecology of Saliva-Derived Polymicrobial Biofilms.

BACKGROUND: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) acts as a salivary biomimetic that provides bioavailable calcium and phosphate ions to augment fluoride-mediated remineralisation of early caries lesions. However, there are indications that it may also have beneficial ecological effects on the oral microbiome. OBJECTIVE: This in vitro study investigated whether CPP-ACP could influence microbial counts, acidogenicity, and the relative abundance of specific caries- and health-associated bacterial -species in polymicrobial biofilms. METHODS: Saliva-derived polymicrobial biofilms were grown for 96 h in a cariogenic environment and treated every 12 h with 2% CPP-ACP or vehicle control. Colony forming units (CFUs) and acidogenicity were estimated from the treated biofilms. Microbial ecological effects of CPP-ACP were assessed based on the relative abundance of 14 specific caries- and health-associated -bacterial species using a real-time quantitative PCR assay. -Results: CPP-ACP-treated biofilms showed relatively modest, but significant, reductions in microbial CFUs (21% reduction, p = 0.008) and acidogenicity (33% reduction, p < 0.001), compared to the control-treated biofilms. The CPP-ACP treated biofilms also exhibited significantly lower bacterial loads of cariogenic Scardovia wiggsiae (fold change 0.017, p < 0.001) and Prevotella denticola(fold change 0.005, p < 0.001), and higher bacterial loads of commensal Streptococcus sanguinis(fold change 30.22, p < 0.001), S. mitis/oralis(fold change 9.66, p = 0.012), and S. salivarius/thermophilus(fold change 89.35, p < 0.001) than the control-treated biofilms. CONCLUSIONS: The results indicate that CPP-ACP has virulence-attenuating attributes that can influence a beneficial microbial ecological change in the biofilm.

Probiotics as Antifungals in Mucosal Candidiasis.

Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections.

Incorporation of Farnesol Significantly Increases the Efficacy of Liposomal Ciprofloxacin against Pseudomonas aeruginosa Biofilms in Vitro.

The challenge of eliminating Pseudomonas aeruginosa infections, such as in cystic fibrosis lungs, remains unchanged due to the rapid development of antibiotic resistance. Poor drug penetration into dense P. aeruginosa biofilms plays a vital role in ineffective clearance of the infection. Thus, the current antibiotic therapy against P. aeruginosa biofilms need to be revisited and alternative antibiofilm strategies need to be invented. Fungal quorum sensing molecule (QSM), farnesol, appears to have detrimental effects on P. aeruginosa. Thus, this study aimed to codeliver naturally occurring QSM farnesol, with the antibiotic ciprofloxacin as a liposomal formulation to eradicate P. aeruginosa biofilms. Four different liposomes (with ciprofloxacin and farnesol, Lcip+far; with ciprofloxacin, Lcip; with farnesol, Lfar; control, Lcon) were prepared using dehydration-rehydration method and characterized. Drug entrapment and release were evaluated by spectrometry and high performance liquid chromatography (HPLC). The efficacy of liposomes was assessed using standard biofilm assay. Liposome-treated 24 h P. aeruginosa biofilms were quantitatively assessed by XTT reduction assay and crystal violet assay, and qualitatively by confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). Ciprofloxacin release from liposomes was higher when encapsulated with farnesol (Lcip+far) compared to Lcip (3.06% vs 1.48%), whereas farnesol release was lower when encapsulated with ciprofloxacin (Lcip+far) compared to Lfar (1.81% vs 4.75%). The biofilm metabolism was significantly lower when treated with Lcip+far or Lcip compared to free ciprofloxacin (XTT, P < 0.05). When administered as Lcip+far, the ciprofloxacin concentration required to achieve similar biofilm inhibition was 125-fold or 10-fold lower compared to free ciprofloxacin or Lcip, respectively (P < 0.05). CLSM and TEM confirmed predominant biofilm disruption, greater dead cell ratio, and increased depth of biofilm killing when treated with Lcip+far compared to other liposomal preparations. Thus, codelivery of farnesol and ciprofloxacin is likely to be a promising approach to battle antibiotic resistant P. aeruginosa biofilms by enhancing biofilm killing at significantly lower antibiotic doses.

Probiotic lactobacilli inhibit early stages of Candida albicans biofilm development by reducing their growth, cell adhesion, and filamentation.

We evaluated the inhibitory effects of the probiotic Lactobacillus species on different phases of Candida albicans biofilm development. Quantification of biofilm growth and ultrastructural analyses were performed on C. albicans biofilms treated with Lactobacillus rhamnosus, Lactobacillus casei, and Lactobacillus acidophilus planktonic cell suspensions as well as their supernatants. Planktonic lactobacilli induced a significant reduction (p < 0.05) in the number of biofilm cells (25.5-61.8 %) depending on the probiotic strain and the biofilm phase. L. rhamnosus supernatants had no significant effect on the mature biofilm (p > 0.05), but significantly reduced the early stages of Candida biofilm formation (p < 0.01). Microscopic analyses revealed that L. rhamnosus suspensions reduced Candida hyphal differentiation, leading to a predominance of budding growth. All lactobacilli negatively impacted C. albicans yeast-to-hyphae differentiation and biofilm formation. The inhibitory effects of the probiotic Lactobacillus on C. albicans entailed both cell-cell interactions and secretion of exometabolites that may impact on pathogenic attributes associated with C. albicans colonization on host surfaces and yeast filamentation. This study clarifies, for the first time, the mechanics of how Lactobacillus species may antagonize C. albicans host colonization. Our data elucidate the inhibitory mechanisms that define the probiotic candicidal activity of lactobacilli, thus supporting their utility as an adjunctive therapeutic mode against mucosal candidal infections.

Improved Biofilm Antimicrobial Activity of Polyethylene Glycol Conjugated Tobramycin Compared to Tobramycin in Pseudomonas aeruginosa Biofilms.

The objective of this study was to develop a functionally enhanced antibiotic that would improve the therapeutic activity against bacterial biofilms. Tobramycin was chemically conjugated with polyethylene glycol (PEG) via site-specific conjugation to form PEGylated-tobramycin (Tob-PEG). The antibacterial efficacy of Tob-PEG, as compared to tobramycin, was assessed on the planktonic phase and biofilms phase of Pseudomonas aeruginosa. The minimum inhibitory concentration (MIC80) of Tob-PEG was higher (13.9 µmol/L) than that of tobramycin (1.4 µmol/L) in the planktonic phases. In contrast, the Tob-PEG was approximately 3.2-fold more effective in eliminating bacterial biofilms than tobramycin. Specifically, Tob-PEG had a MIC80 lower than those exhibited by tobramycin (27.8 µmol/L vs 89.8 µmol/L). Both confocal laser scanning microscopy and scanning electron microscopy further confirmed these data. Thus, modification of antimicrobials by PEGylation appears to be a promising approach for overcoming the bacterial resistance in the established biofilms of Pseudomonas aeruginosa.

Magnetic fields suppress Pseudomonas aeruginosa biofilms and enhance ciprofloxacin activity.

Due to the refractory nature of pathogenic microbial biofilms, innovative biofilm eradication strategies are constantly being sought. Thus, this study addresses a novel approach to eradicate Pseudomonas aeruginosa biofilms. Magnetic nanoparticles (MNP), ciprofloxacin (Cipro), and magnetic fields were systematically evaluated in vitro for their relative anti-biofilm contributions. Twenty-four-hour biofilms exposed to aerosolized MNPs, Cipro, or a combination of both, were assessed in the presence or absence of magnetic fields (Static one-sided, Static switched, Oscillating, Static + oscillating) using changes in bacterial metabolism, biofilm biomass, and biofilm imaging. The biofilms exposed to magnetic fields alone exhibited significant metabolic and biomass reductions (p < 0.05). When biofilms were treated with a MNP/Cipro combination, the most significant metabolic and biomass reductions were observed when exposed to static switched magnetic fields (p < 0.05). The exposure of P. aeruginosa biofilms to a static switched magnetic field alone, or co-administration with MNP/Cipro/MNP + Cipro appears to be a promising approach to eradicate biofilms of this bacterium.

Sub-inhibitory concentrations of antifungals suppress hemolysin activity of oral Candida albicans and Candida tropicalis isolates from HIV-infected individuals.

Secretion of hydrolytic enzymes such as hemolysin is considered an important virulence attribute of the opportunistic pathogenic fungus Candida. It is known that Candida spp. isolated from HIV-infected patients produce copious hemolysins. As common antifungal agents may perturb the production of extracellular enzymes, we evaluated the effect of three antifungals nystatin, amphotericin B and fluconazole on the hemolytic activity of Candida albicans and Candida tropicalis isolates from HIV-infected individuals. The impact of antimycotics on hemolytic activity was assessed by a previously described in vitro plate assay, after exposing ten isolates each of C. albicans and C. tropicalis recovered from HIV-infected individuals to sub-minimum inhibitory concentrations (sub-MIC) of nystatin, amphotericin B and fluconazole. All Candida isolates showed a significant reduction in hemolytic activity. The reduction was highest for amphotericin B-exposed C. albicans and C. tropicalis followed by nystatin and fluconazole. The effect of antimycotics was more pronounced on the hemolytic activity of C. tropicalis compared to that of C. albicans. Commonly used antifungal agents significantly suppress hemolysin activity of Candida species. This implies that the antifungals, in addition to their lethality, may modulate key virulence attributes of the yeast. The clinical relevance of this phenomenon in HIV disease and other similar pathologies remains to be determined.

Sound waves effectively assist tobramycin in elimination of Pseudomonas aeruginosa biofilms in vitro.

Microbial biofilms are highly refractory to antimicrobials. The aim of this study was to investigate the use of low-frequency vibration therapy (20-20 kHz) on antibiotic-mediated Pseudomonas aeruginosa biofilm eradication. In screening studies, low-frequency vibrations were applied on model biofilm compositions to identify conditions in which surface standing waves were observed. Alginate surface tension and viscosity were also measured. The effect of vibration on P. aeruginosa biofilms was studied using a standard biofilm assay. Subminimal inhibitory concentrations (sub-MIC) of tobramycin (5 µg/ml) were added to biofilms 3 h prior, during, and immediately after vibration and quantitatively assessed by (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reduction assay (XTT) and, qualitatively, by confocal laser scanning microscopy (CLSM). The standing waves occurred at frequencies <1,000 Hz. Biofilms vibrated without sub-MIC tobramycin showed a significantly reduced metabolism compared to untreated controls (p < 0.05). Biofilms treated with tobramycin and vibrated simultaneously (450, 530, 610, and 650 Hz), or vibrated (450 and 650 Hz) then treated with tobramycin subsequently, or vibrated (610 Hz, 650 Hz) after 3 h of tobramycin treatment showed significantly lower metabolism compared to P. aeruginosa biofilm treated with tobramycin alone (p < 0.05). CLSM imaging further confirmed these findings. Low frequency vibrations assisted tobramycin in killing P. aeruginosa biofilms at sub-MIC. Thus, sound waves together with antibiotics are a promising approach in eliminating pathogenic biofilms.

Mucormycosis-causing fungi in humans: a meta-analysis establishing the phylogenetic relationships using internal transcribed spacer (ITS) sequences.

Introduction. Mucormycosis is a severe angio-invasive fungal infection caused by mucormycetes, a group of fungi that are ubiquitous in the environment. The incidence of mucormycosis has been surging rapidly due to the global corona virus disease 2019 (COVID-19) pandemic.Gap Statement. The complete picture of the causative fungi associated with mucormycosis and their phylogenetic relationships are not well defined.Aim. This meta-analysis aimed to collate all confirmed fungal pathogens that cause mucormycosis, and assess their taxonomic relationships.Methodology. All types of articles in the PubMed database that report fungi as a cause of mucormycosis were reviewed. We summarized the fungal morphological characteristic up to the genus level. The internal transcribed spacer (ITS) nucleotide sequences of these fungi were retrieved from the National Center for Biotechnology Information (NCBI) and UNITE databases whenever available, and multiple sequence analysis was conducted using Clustal W. The phylogenetic tree was constructed using mega version 7.Results. Forty-seven fungal species were identified as pathogens causing mucormycosis in humans. Thirty-two fungal species were phylogenetically grouped into three clades, and it was evident that the ITS sequences have well-conserved regions in all clades, especially from the 400th to 500th base pairs.Conclusion. The findings of this work contribute to the descriptive data for fungi that cause mucormycosis, emphasizing the need for robust phylogenetic approaches when identifying clinical isolates from infected patients.

Microbial chemical signaling: a current perspective.

Communication among microorganisms is mediated through quorum sensing. The latter is defined as cell-density linked, coordinated gene expression in microbial populations as a response to threshold signal concentrations followed by induction of a synchronized population response. This phenomenon is used by a variety of microbes to optimize their survival in a constantly challenging, dynamic milieu, by correlating individual cellular functions to community-based requirements. The synthesis, secretion, and perception of quorum-sensing molecules and their target response play a pivotal role in quorum sensing and are tightly controlled by complex, multilayered and interconnected signal transduction pathways that regulate diverse cellular functions. Quorum sensing exemplifies interactive social behavior innate to the microbial world that controls features such as, virulence, biofilm maturation, antibiotic resistance, swarming motility, and conjugal plasmid transfer. Over the past two decades, studies have been performed to rationalize bacterial cell-to-cell communication mediated by structurally and functionally diverse small molecules. This review describes the theoretical aspects of cellular and quorum-sensing mechanisms that affect microbial physiology and pathobiology.

Oral health promotion interventions on oral reservoirs of staphylococcus aureus: a systematic review.

The oral cavity serves as a reservoir of Staphylococcus aureus for infection of the lower respiratory tract and cross-infection to other patients. This systematic review was designed to examine the effectiveness of oral health promotion interventions on this pathogen. The PubMed, ISI Web of Science, and Cochrane Library databases were searched for clinical trials assessing the effect of oral health promotion interventions on oral and oropharyngeal carriage of S. aureus. Oral health promotion interventions on oral reservoirs of S. aureus in both systemically healthy and medically compromised groups consisted of oral hygiene interventions only. There was a lack of evidence pertaining to the effectiveness of mechanical oral hygiene interventions against this pathogen. Chlorhexidine delivered in oral hygiene products such as mouthrinses, gels, and sprays appeared to have some utility against S. aureus, although some studies found equivocal effects. There was a dearth of studies investigating the efficacy of other chemical agents. Although many chemical agents contained in oral hygiene products have proven in vitro activity against S. aureus, their clinical effectiveness and potential role as adjuncts or alternative therapies to conventional treatment remain to be confirmed by further high-quality randomized controlled trials.

Oral health promotion interventions on oral yeast in hospitalised and medically compromised patients: a systematic review.

Yeast are major aetiological agents of localised oral mucosal lesions, and are also leading causes of nosocomial bloodstream infections. The purpose of this systematic review was to examine the effectiveness of oral health promotion interventions on the prevalence and incidence of these opportunistic oral pathogens in hospitalised and medically compromised patients. The PubMed, ISI Web of Science and Cochrane Library databases were searched for clinical trials assessing the effect of oral health promotion interventions on oral yeast. Chlorhexidine delivered in a variety of oral hygiene products appeared to have some effect on oral yeast, although some studies found equivocal effects. Although a wide array of other compounds have also been investigated, their clinical effectiveness remains to be substantiated. Likewise, the utility of mechanical oral hygiene interventions and other oral health promotion measures such as topical application of salivary substitute, remains unsettled. Although many chemical agents contained in oral hygiene products have proven in vitro activity against oral yeast, their clinical effectiveness and potential role as adjuncts or alternative therapies to conventional treatment remains to be confirmed by further high-quality randomised controlled trials. This is pertinent, given the recent emergence of yeast resistance to conventional antifungal agents.

Emerging strategies for environmental decontamination of the nosocomial fungal pathogen Candida auris.

Candida auris is a recently emerged multidrug-resistant fungal pathogen that causes life-threatening infections to the human population worldwide. Recent rampant outbreaks of C. auris in coronavirus disease 2019 (COVID-19) patients, together with outbreaks in over 45 countries, highlight its threat to patients and healthcare economies. Unlike other pathogenic Candida species, C. auris is capable of surviving in abiotic surfaces of healthcare facilities for prolonged periods, leading to increased risk of transmission within nosocomial settings. C. auris is resistant to multiple classes of antifungal agents, forms dry biofilms and transmits independently to regional epicentres, making its eradication from nosocomial environment arduous. The lack of strategies for environmental decontamination of C. auris from nosocomial settings is evident from the generic guidance and recommendations provided by leading global healthcare bodies. Therefore, this minireview discusses the current guidelines for environmental decontamination of C. auris and compounds and strategies currently under investigation for potential future use. While established guidelines recommend the use of products mainly consisting of sodium hypochlorite and hydrogen peroxide, initial works have been reported on the promising anti-C. auris properties of various other compounds and some biocompatible alternatives. Further validation of these approaches, coupled up with environmentally friendly decontamination protocols, are warranted to achieve superior elimination of C. auris from healthcare settings.

Nitrogen doped titanium dioxide as an aesthetic antimicrobial filler in dental polymers.

OBJECTIVE: To develop an aesthetic resin composite using a nitrogen-doped titanium dioxide (NTiO2) filler that possesses antimicrobial properties against cariogenic bacteria. METHODS: N-TiO2 powder was manufactured by calcining commercial TiO2 with urea. Free radical release from the N-TiO2 powder under visible light irradiation was analysed using UV-Vis spectrophotometry. The N-TiO2 powder was incorporated into a dental resin and the photocatalytic activity assessed using a dye under both visible light and dark conditions. Using XTT assay to measure the cellular metabolic activity, the antibacterial properties of the N-TiO2 /resin composite discs were tested using Streptococcus mutans. RESULTS: Doping nitrogen of TiO2 resulted in a band gap shift towards the visible light spectrum, which enabled the powder to release reactive oxygen species when exposed to visible light. When incorporated into a dental resin, the N-TiO2/resin composite still demonstrated sustained release of reactive oxygen species, maintaining its photocatalytic activity and showing an antibacterial effect towards Streptococcus mutans under visible light conditions. SIGNIFICANCE: N-TiO2 filled resin composite shows great promise as a potential aesthetic resin based adhesive for orthodontic bonding.

Pseudomonas aeruginosa inhibits in-vitro Candida biofilm development.

BACKGROUND: Elucidation of the communal behavior of microbes in mixed species biofilms may have a major impact on understanding infectious diseases and for the therapeutics. Although, the structure and the properties of monospecies biofilms and their role in disease have been extensively studied during the last decade, the interactions within mixed biofilms consisting of bacteria and fungi such as Candida spp. have not been illustrated in depth. Hence, the aim of this study was to evaluate the interspecies interactions of Pseudomonas aeruginosa and six different species of Candida comprising C. albicans, C. glabrata, C. krusei, C. tropicalis, C. parapsilosis, and C. dubliniensis in dual species biofilm development. RESULTS: A significant reduction in colony forming units (CFU) of C. parapsilosis (90 min), C. albicans and C. tropicalis (90 min, 24 h and 48 h), C. dubliniensis and C. glabrata, (24 h and 48 h) was noted when co-cultured with P. aeruginosa in comparison to their monospecies counterparts (P < 0.05). A simultaneous significant reduction in P. aeruginosa numbers grown with C. albicans (90 min and 48 h), C. krusei (90 min, 24 h and 48 h),C. glabrata, (24 h and 48 h), and an elevation of P. aeruginosa numbers co-cultured with C. tropicalis (48 h) was noted (P < 0.05). When data from all Candida spp. and P. aeruginosa were pooled, highly significant mutual inhibition of biofilm formation was noted (Candida P < 0.001, P. aeruginosa P < 0.01). Scanning Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) analyses confirmed scanty architecture in dual species biofilm in spite of dense colonization in monospecies counterparts. CONCLUSIONS: P. aeruginosa and Candida in a dual species environment mutually suppress biofilm development, both quantitatively and qualitatively. These findings provide a foundation to clarify the molecular basis of bacterial-fungal interactions, and to understand the pathobiology of mixed bacterial-fungal infections.

Fluconazole resistance in Candida albicans is induced by Pseudomonas aeruginosa quorum sensing.

Microorganisms employ quorum sensing (QS) mechanisms to communicate with each other within microbial ecosystems. Emerging evidence suggests that intraspecies and interspecies QS plays an important role in antimicrobial resistance in microbial communities. However, the relationship between interkingdom QS and antimicrobial resistance is largely unknown. Here, we demonstrate that interkingdom QS interactions between a bacterium, Pseudomonas aeruginosa and a yeast, Candida albicans, induce the resistance of the latter to a widely used antifungal fluconazole. Phenotypic, transcriptomic, and proteomic analyses reveal that P. aeruginosa's main QS molecule, N-(3-Oxododecanoyl)-L-homoserine lactone, induces candidal resistance to fluconazole by reversing the antifungal's effect on the ergosterol biosynthesis pathway. Accessory resistance mechanisms including upregulation of C. albicans drug-efflux, regulation of oxidative stress response, and maintenance of cell membrane integrity, further confirm this phenomenon. These findings demonstrate that P. aeruginosa QS molecules may confer protection to neighboring yeasts against azoles, in turn strengthening their co-existence in hostile polymicrobial infection sites.

Randomized Controlled Study to Evaluate Microbial Ecological Effects of CPP-ACP and Cranberry on Dental Plaque.

INTRODUCTION: Ecological approaches to dental caries prevention play a key role in attaining long-term control over the disease and maintaining a symbiotic oral microbiome. OBJECTIVES: This study aimed to investigate the microbial ecological effects of 2 interventional dentifrices: a casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) dentifrice and the same dentifrice supplemented with a polyphenol-rich cranberry extract. METHODS: The interventional toothpastes were compared with each other and with an active control fluoride dentifrice in a double-blinded randomized controlled trial. Real-time quantitative polymerase chain reaction (qPCR) analysis was used to determine changes in the bacterial loads of 14 key bacterial species (8 caries associated and 6 health associated) in the dental plaque of trial participants after they used the dentifrices for 5 to 6 wk. RESULTS: From the baseline to the recall visit, significant differences were observed between the treatment groups in the bacterial loads of 2 caries-associated bacterial species (Streptococcus mutans [P < 0.001] and Veillonella parvula [P < 0.001]) and 3 health-associated bacterial species (Corynebacterium durum [P = 0.008], Neisseria flavescens [P = 0.005], and Streptococcus sanguinis [P < 0.001]). Compared to the fluoride control dentifrice, the CPP-ACP dentifrice demonstrated significant differences for S. mutans (P = 0.032), C. durum (P = 0.007), and S. sanguinis (P < 0.001), while combination CPP-ACP-cranberry dentifrice showed significant differences for S. mutans (P < 0.001), V. parvula (P < 0.001), N. flavescens (P = 0.003), and S. sanguinis (P < 0.001). However, no significant differences were observed in the bacterial load comparisons between the CPP-ACP and combination dentifrices for any of the targeted bacterial species (P > 0.05). CONCLUSIONS: Overall, the results indicate that dentifrices containing CPP-ACP and polyphenol-rich cranberry extracts can influence a species-level shift in the ecology of the oral microbiome, resulting in a microbial community less associated with dental caries (Australian New Zealand Clinical Trial Registry ANZCTR 12618000095268). KNOWLEDGE TRANSFER STATEMENT: The results of this randomized controlled trial indicate that dentifrices containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and polyphenol-rich cranberry extracts were able to beneficially modulate the microbial ecology of dental plaque in a group of high caries-risk patients. This could contribute toward lowering the risk of developing new caries lesions, an important goal sought by patients, clinicians, and policy makers.