1,3,5-Triazine as Branching Connector for the Construction of Novel Antimicrobial Peptide Dendrimers: Synthesis and Biological Characterization.

Peptides displaying antimicrobial properties are being regarded as useful tools to evade and combat antimicrobial resistance, a major public health challenge. Here we have addressed dendrimers, attractive molecules in pharmaceutical innovation and development displaying broad biological activity. Triazine-based dendrimers were fully synthesized in the solid phase, and their antimicrobial activity and some insights into their mechanisms of action were explored. Triazine is present in a large number of compounds with highly diverse biological targets with broad biological activities and could be an excellent branching unit to accommodate peptides. Our results show that the novel peptide dendrimers synthesized have remarkable antimicrobial activity against Gram-negative bacteria (E. coli and P. aeruginosa) and suggest that they may be useful in neutralizing the effect of efflux machinery on resistance.

Colistin Enhances Rifampicin's Antimicrobial Action in Colistin-Resistant Pseudomonas aeruginosa Biofilms.

The emergence of multidrug-resistant Pseudomonas aeruginosa infections has urged the need to find new strategies, such as the use of combinations of antibiotics. Among these, the combination of colistin with other antibiotics has been studied. Here, the action of combinations of colistin and rifampicin on both planktonic and sessile cells of colistin-resistant P. aeruginosa was studied. Dynamic biofilms were formed and treated with such a combination, resulting in an active killing effect of both colistin-resistant and colistin-susceptible P. aeruginosa in biofilms. The results suggest that the action of colistin on the outer membrane facilitates rifampicin penetration, regardless of the colistin-resistant phenotype. Based on these in vitro data, we propose a colistin-rifampicin combination as a promising treatment for infections caused by colistin-resistant P. aeruginosa.

Substantivity of mouth-rinse formulations containing cetylpyridinium chloride and O-cymen-5-ol: a randomized-crossover trial.

BACKGROUND: The efficacy of mouth-rinses strongly depends upon their substantivity. The use of natural and non-toxic products that avoid secondary effects is gaining interest in preventive dentistry. The purpose of this study was to evaluate the substantivity of two formulations of mouth-washing solutions based on cetylpyridinium (CPC) and O-cymen-5-ol. METHODS: This was a randomized, double-blind, crossover trial conducted at the Faculty of Medicine and Health Sciences of the University of Barcelona. Bacterial re-colonization was followed by live/dead (SYTOTM9 + propidium iodide) bacterial staining and measured by confocal laser scanning microscopy and fluorometry. Unstimulated saliva samples were collected from 16 healthy individuals at baseline saliva and then, at 15 min, 30 min and 1, 2, 3, and 4 h after the following mouth-rinses: (i) a single, 1-min mouth-rinse with 15 ml of placebo (negative control); (ii) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) ; (iii) a single, 1-min mouth-rinse with 15 ml of O-cymen-5-ol (0.09%); (iv) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) + O-cymen-5-ol (0.09%). RESULTS: Proportion of dead bacteria was significantly higher for all mouthrinses during the first 15 min compared to baseline (CPC = 48.0 ± 13.9; 95% CI 40.98-56.99; p < 0.001, O-cymen-5-ol = 79.8 ± 21.0; 95% CI 67.71-91.90; p < 0.05, CPC + O-cymen-5-ol = 49.4 ± 14; 95% CI 40.98-56.99; p < 0.001 by fluorometry and 54.8 ± 23.0; 95% CI 41.50-68.06; p < 0.001, 76.3 ± 17.1; 95% CI 66.36-86.14; p < 0.001, 47.4 ± 11.9; 95% CI 40.49-54.30; p < 0.001 by confocal laser scanning microscopy, respectively). Nevertheless, after 4 h, CPC + O-cymen-5-ol was the only one that obtained significant values as measured by the two quantification methods used (80.3 ± 22.8; 95% CI 67.15-93.50; p < 0.05 and 81.4 ± 13.8; 95% CI 73.45-89.43; p < 0.05). The combined use of CPC + O-cymen-5-ol increased the substantivity of the mouthrinse with respect to mouthrinses prepared with either of the two active products alone. CONCLUSION: The synergistic interaction of CPC and O-cymen-5-ol prolongs their substantivity. The resulting formulation may be as effective as other antimicrobials, such as triclosan or chlorhexidine, but without their undesirable secondary effects. Thus, mouthrinsing products based on Combinations of CPC and O-cymen-5-ol may replace in the near future Triclosan and Chlorhexidine-based mouthrinses.

Chemical Modification of Microcin J25 Reveals New Insights on the Stereospecific Requirements for Antimicrobial Activity.

In this study, microcin J25, a potent antimicrobial lasso peptide that acts on Gram-negative bacteria, was subjected to a harsh treatment with a base in order to interrogate its stability and mechanism of action and explore its structure-activity relationship. Despite the high stability reported for this lasso peptide, the chemical treatment led to the detection of a new product. Structural studies revealed that this product retained the lasso topology, but showed no antimicrobial activity due to the epimerization of a key residue for the activity. Further microbiological assays also demonstrated that it showed a high synergistic effect with colistin.

Novel synthetic polymyxins kill Gram-positive bacteria.

Background: Staphylococcus aureus, including 'superbug' MRSA, is a major cause of nosocomial infections. In the European Union, up to 171 200 new nosocomial MRSA infections are acquired annually, and in the USA S. aureus causes more deaths than HIV/AIDS and tuberculosis combined. MRSA is also the first group of pathogens that infect the pulmonary tract in young patients with cystic fibrosis. Objectives: We describe two newly developed and synthesized colistin (polymyxin E)-inspired molecules. Methods: A collection of several isolates of S. aureus [including MRSA and vancomycin-resistant S. aureus (VRSA)] was tested. To check the antimicrobial activity, we performed time-kill curves, growth curves, biofilm eradication, toxicity and isothermal titration calorimetry. Results: Both peptides showed high antimicrobial activities (MIC 4 mg/L) and low relative toxicities (selectivity index close to 23). Conclusions: Successful production of polymyxin-scaffold molecules active against S. aureus, both MRSA and VRSA, opens up new approaches to the treatment of these complicated infections.

Benefits of non-surgical periodontal treatment in patients with type 2 diabetes mellitus and chronic periodontitis: A randomized controlled trial.

BACKGROUND: Periodontitis and diabetes are highly prevalent conditions whose association has long been recognized. OBJECTIVE: To evaluate the effect of non-surgical periodontal treatment on serum HbA1c (haemoglobin A1c or glycated haemoglobin) levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a 6-month, single-masked, randomized clinical trial based on 90 patients (HbA1c: 7.7% (61 mmol/mol) ± 1.13%) who were randomly assigned to either the treatment group (oral hygiene instructions + scaling and root planing using ultrasound and Gracey curettes) or the control group (oral hygiene instructions + supragingival removal of plaque and calculus using ultrasound). Pocket depth, gingival index, and plaque index were assessed at baseline and after 3 and 6 months together with determinations of fasting plasma glucose, HbA1c, and bacterial counts. RESULTS: Treatment significantly improved the periodontal and metabolic parameters (p < .05), whereas in the control group no improvement was observed. These results were consistent with the bacteriological results in most but not all cases. CONCLUSION: Non-surgical periodontal treatment resulted in a better glycaemic status of type 2 diabetes patients and demonstrated the importance of oral health in their general health.

Clinical laser treatment of toenail onychomycoses.

Onychomycoses are fungal infections of the fingernails or toenails having a prevalence of 3% among adults and accounts for 50% of nail infections. It is caused by dermatophytes, non-dermatophyte filamentous fungi, and yeasts. Compressions and microtraumas significantly contribute to onychomycosis. Laser and photodynamic therapies are being proposed to treat onychomycosis. Laser light (1064 nm) was used to treat onychomycosis in 156 affected toenails. Patients were clinically followed up for 9 months after treatment. Microbiological detection of fungal presence in lesions was accomplished. A total of 116 samples allowed the isolation of at least a fungus. Most of nails were affected in more than two thirds surface (some of them in the full surface). In 85% of cases, after 18 months of the onset of treatment, culture turned negative. After 3 months months, only five patients were completely symptom-free with negative culture. In 25 patients, only after 6 months, the absence of symptoms was achieved and the cultures negativized; in 29 patients, 9 months were required. No noticeable adverse effects were reported. This study reinforces previous works suggesting the applicability of laser therapies to treat toenail onychomycosis.

Human papillomaviruses genotyping in plantar warts.

Plantar warts are caused by human papillomaviruses (HPVs) and have been associated with several HPV genotypes. However, there are few studies focused exclusively on plantar warts. In this work, we aim to identify the HPV genotypes of plantar warts and explore their relation to demographic and clinical characteristics of patients. A total of 72 patients diagnosed with plantar warts were recruited at the Laser unit at Podiatric Hospital, University of Barcelona, Spain. Inner hyperkeratosis laminar sections of warts were collected and DNA of samples were extracted. Amplification of a conserved region of the HPV L1 gene was performed with the SK-Polymerase chain reaction method. DNA amplicons were sequenced and HPV types identified. The most prevalent genotypes detected among the 105 analyzed plantar warts were HPV-57 (37.1%), HPV-27 (23.8%), HPV-1a (20.9%), HPV-2 (15.2%), and HPV-65 (2.8%). The majority of patients (78%) presented one single plantar wart, whereas multiple warts were detected in 22.2% of patients. One patient with multiple warts presented HPV types from two different genera, suggesting the spread of warts by self-inoculation as well as by de novo infection. No significant differences between the number of warts in toes, midfoot and heel were found. The most prevalent HPV types detected in all areas belonged to the alpha genus. This work provides new insight on plantar warts and their associated HPV genotypes, and evidences the usefulness and reliability of both the sample collection procedure and the PCR method used for HPV detection and typing. J. Med. Virol. 89:902-907, 2017. © 2016 Wiley Periodicals, Inc.

Transcriptomics as a tool to discover new antibacterial targets.

The emergence of antibiotic-resistant pathogens, multiple drug-resistance, and extremely drug-resistant strains demonstrates the need for improved strategies to discover new drug-based compounds. The development of transcriptomics, proteomics, and metabolomics has provided new tools for global studies of living organisms. However, the compendium of expression profiles produced by these methods has introduced new scientific challenges into antimicrobial research. In this review, we discuss the practical value of transcriptomic techniques as well as their difficulties and pitfalls. We advocate the construction of new databases of transcriptomic data, using standardized formats in addition to standardized models of bacterial and yeast similar to those used in systems biology. The inclusion of proteomic and metabolomic data is also essential, as the resulting networks can provide a landscape to rationally predict and exploit new drug targets and to understand drug synergies.

Status of Removable Dentures and Relationship with Oral Candida-Associated Factors in a Geriatric Population in Catalonia.

PURPOSE: Colonization by Candida is related to wearing a denture. How denture type, status, and maintenance play a role in determining Candida colonization remains unknown. This work evaluated removable denture status in an elderly population and explored the association between denture-related factors and oral Candida colonization as determined by systemic and local factors. MATERIALS AND METHODS: Socio-demographic, general health, and behavioral data and oral factors were registered by means of a questionnaire. Oral, dental, and denture-related factors were assessed by clinical examination, and yeasts were isolated from oral and denture specimens. Multiple logistic regression analysis was used to explore the relative relevance of risk factors. RESULTS: Overall, 52.4% of subjects used complete dentures in both lower and upper arches, and 90% of the prostheses were in good condition. Denture plaque index was high in most cases, and 75% of subjects had yeasts in their oral cavities. Oral Candida colonization was significantly associated with low saliva pH, sugar consumption, and the fault of a denture component; however, only sugar consumption was found to be an independent factor related with oral Candida colonization, showing an odds ratio of 3.04 in a multiple logistic regression model. CONCLUSIONS: Elderly people in this study used a complete denture in good condition, with a median age of 15 years. Daily or weekly sugar consumption was found to be highly associated with oral colonization by Candida.

Bacteremia Associated With Oral Surgery: A Review.

OBJECTIVES: Bacterial (infective) endocarditis, a microbial infection of the endocardium surfaces after bacteremia, causes significant morbidity and mortality. Recent epidemiologic studies have reported a prevalence of 2-8 cases per 100,000 individuals per year, with the highest incidence in those aged 70-80 years and those living in developed countries. We systematically reviewed the literature on several critical aspects regarding the development of bacteremia after oral surgery. The purpose of this work is to assess the controversy regarding antibiotic prophylaxis before oral surgery. MATERIALS AND METHODS: Publications between 1976 and 2015 were included. Clinical studies focusing on oral surgery as the underlying cause were included. RESULTS: Among the 32 clinical studies reviewed, 3564 cases, accounting for 12,839 blood cultures, were evaluated. In 10 of these studies, amoxicillin usefulness was studied. Antimicrobial prophylaxis before an invasive dental procedure does not prevent bacteremia, although it can decrease both its magnitude and its persistence. CONCLUSIONS: The highly conflicting data and conclusions of the analyzed work highlight the need for new approaches to the study of bacteremia that would provide reliable evidence and thus appropriate prophylactic and therapeutic standards. Many reports have explored the occurrence of bacteremia after dental procedures, but the results have been conflicting.

Synergistic Antipseudomonal Effects of Synthetic Peptide AMP38 and Carbapenems.

The aim was to explore the antimicrobial activity of a synthetic peptide (AMP38) and its synergy with imipenem against imipenem-resistant Pseudomonas aeruginosa. The main mechanism of imipenem resistance is the loss or alteration of protein OprD. Time-kill and minimal biofilm eradication concentration (MBEC) determinations were carried out by using clinical imipenem-resistant strains. AMP38 was markedly synergistic with imipenem when determined in imipenem-resistant P. aeruginosa. MBEC obtained for the combination of AMP38 and imipenem was of 62.5 µg/mL, whereas the MBEC of each antimicrobial separately was 500 µg/mL. AMP38 should be regarded as a promising antimicrobial to fight MDR P. aeruginosa infections. Moreover, killing effect and antibiofilm activity of AMP38 plus imipenem was much higher than that of colistin plus imipenem.

Effect of nonsurgical periodontal treatment on glycosylated hemoglobin in diabetic patients: a systematic review.

This review was designed to determine whether non-surgical periodontal treatment is able to reduce serum glycosylated hemoglobin (HbA1c) levels in patients with diabetes mellitus (DM). Several previous reports showed that scaling and root planning (SRP) improve periodontal status in patients with DM, but whether it also improves metabolic control of the disease is unclear. A systematic review was conducted according to the recommendations of the Cochrane Collaboration and PRISMA. A literature search was conducted in October 2012 using three libraries (Cochrane, Web of Knowledge, and Scopus) and the keywords "periodontal disease" and "diabetes mellitus." Only 21 of the articles met the inclusion criteria for this review. A total of 1,454 patients were thus included in this study to evaluate whether periodontal treatment improved serum HbA1c levels. Both the methodological quality and the risk of bias of each study were taken into account using the Jadad scale. Only ten of the included studies had an acceptable-good score of 3-5. Fourteen of the studies reported a significant decrease in serum HbA1c levels (p < 0.05) after periodontal treatment. The remaining seven studies failed to find a significant decrease in serum HbA1c. The findings of this review suggest that the published literature is insufficient and inconclusive to clearly support periodontal treatment as a means to improve serum HbA1c levels in patients with type 1 DM. It also demonstrates the need for homogeneous studies, with larger samples and longer follow-up periods, to properly address this question.

Atomic force microscopy visualization of injuries in Enterococcus faecalis surface caused by Er,Cr:YSGG and diode lasers.

AIM: To visualize by atomic force microscopy the alterations induced on Enterococcus. faecalis surface after treatment with 2 types of laser: Erbium chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser and Diode laser. MATERIAL AND METHODS: Bacterial suspensions from overnight cultures of E. faecalis were irradiated during 30 seconds with the laser-lights at 1 W and 2 W of power, leaving one untreated sample as control. Surface alterations on treated E. faecalis were visualized by atomic force microscopy (AFM) and its surface roughness determined. RESULTS: AFM imaging showed that at high potency of laser both cell morphology and surface roughness resulted altered, and that several cell lysis signs were easily visualized. Surface roughness clearly increase after the treatment with Er,Cr:YSGG at 2W of power, while the other treatments gave similar values of surface roughness. The effect of lasers on bacterial surfaces visualized by AFM revealed drastic alterations. CONCLUSIONS: AFM is a good tool to evaluate surface injuries after laser treatment; and could constitute a measure of antimicrobial effect that can complete data obtained by determination of microbial viability.

Load-Bearing Capacity of Fiber-Reinforced Composite Abutments and One-Piece Implants.

Fiber-reinforced composites (FRC) can potentially help in a physiologic stress transmission due to its excellent biomechanical matching with living tissues. Novel one-piece FRC implants and abutments with two different fiber orientations were loaded until failure to assess the load-bearing capacity, fracture patterns, and precision of fit. The one-piece FRC implants showed significantly higher load-bearing capacity compared to FRC abutments regardless of the fiber orientation (p < 0.001). For FRC abutments, bidirectional abutments showed significantly higher loads compared to unidirectional abutments (p < 0.001). The type of structure and fiber orientation are strong determinant factors of the load-bearing capacity of FRC implants and abutments.

Risk factors for denture-related oral mucosal lesions in a geriatric population.

STATEMENT OF PROBLEM: Denture-related mucosal lesions have been broadly studied. However, no consensus has been reached regarding the risk factors associated with these lesions, and few studies have used multivariable analysis to determine the relative significance of different risks. PURPOSE: The purpose of this study was to determine the relationship between systemic, local, and denture factors on the risk of denture-related oral mucosal lesions in an elderly population by using multivariable analysis. MATERIAL AND METHODS: Eighty-four elderly denture wearers recruited from geriatric residences and day care centers participated in this cross-sectional study. All data were obtained by means of a questionnaire-interview, a physical examination, and complementary tests. Bivariate relationship and multiple logistic regression analyses were performed (α=.05). RESULTS: Angular cheilitis (34%), traumatic ulcers (15%), and denture stomatitis (14%) were the 3 most common lesions, and the prevalence of at least 1 denture-related mucosal lesion was 54%. The presence of denture stomatitis was related to low saliva pH, never having smoked, and regular sugar consumption. Angular cheilitis was associated with age, complete edentulism, the presence of oral Candida, a lack of denture stability, and a reduced occlusal vertical dimension. The presence of traumatic ulcers was related to a resorbed residual alveolar ridge. The presence of at least 1 lesion was associated with poor masticatory efficiency, being resident in a care facility, oral Candida, and a lack of denture stability. CONCLUSIONS: Several systemic, local, and denture-related characteristics are independent risk factors for denture-related mucosal lesions in an elderly population.

Progress towards the clinical use of antimicrobial peptides: challenges and opportunities.

INTRODUCTION: To overcome the challenge of multidrug resistance, natural and synthetic peptides are candidates to become the basis of innovative therapeutics, featuring diverse mechanisms of action. Traditionally, the time elapsed from medical discoveries to their application is long. The urgency derived from the emergence of antibiotic resistance recommends an acceleration of research to put the new weapons in the hands of clinicians. AREAS COVERED: This narrative review introduces ideas and suggestions of new strategies that may be used as a basis upon which to recommend reduced development times and to facilitate the arrival of new molecules in the fight against microbes. EXPERT OPINION: Although studies on new innovative antimicrobial treatments are being conducted, sooner rather than later, more clinical trials, preclinical and translational research are needed to promote the development of innovative antimicrobial treatments for multidrug resistant infections. The situation is worrying, no less than that generated by pandemics such as the ones we have just experienced and conflicts such as world wars. Although from the point of view of human perception, resistance to antibiotics may not seem as serious as these other situations, it is possibly the hidden pandemic that most jeopardizes the future of medicine.

Native Pig Neutrophil Products: Insights into Their Antimicrobial Activity.

Cationic antimicrobial peptides are molecules with potential applications for treating infections due to their antimicrobial and immunomodulatory properties. The aim of this work was to explore the antimicrobial activity and mechanisms of action of a porcine neutrophil cathelicidin mixture (MPPN). Gram-positive and Gram-negative bacteria were used to determine the minimum inhibitory concentration (MIC) and experiments of both time-kill kinetics and effects on growth curves were performed. Planar black lipid bilayer conductance was measured to analyze the interaction of MPPN with lipid bilayers. Visualization of bacterial surfaces and membrane alterations was achieved using atomic force microscopy and transmission electron microscopy. The effects on the activity of efflux pumps (EPs) were studied with an intracellular accumulation of acridine orange (AO) assay. In E. coli, MPPN behaves as a bactericide at high concentrations and as a bacteriostatic at lower concentrations. The bacteriostatic effect was also observed for slightly shorter periods in S. enterica. The mixture was not active on S. aureus. The increase in AO accumulation in the presence of MPPN indicates that, at least in E. coli, the mixture causes inhibition of the EP function. Observed and detected variable conductance events demonstrate a strong MPPN effect on lipid bilayers. Damage to the structure of treated E. coli indicates that MPPN induces alterations in the bacterial surface. The use of AMPs capable of inhibiting EP can be seen as a good tool to combat antimicrobial resistance since they could be used alone or in combination with other conventional antibiotics to which bacteria have become resistant.

Efficient AntiMycolata Agents by Increasing the Lipophilicity of Known Antibiotics through Multicomponent Reactions.

New antibiotic agents were prepared using Povarov and Ugi multicomponent reactions upon the known drugs sulfadoxine and dapsone. The prepared derivatives, with increased lipophilicity, showed improved efficiency against Mycolata bacteria. Microbiological guidance for medicinal chemistry is a powerful tool to design new and effective antimicrobials. In this case, the readily synthesized compounds open new possibilities in the search for antimicrobials active on mycolic acid-containing bacteria.

Antimicrobial Activity of Selenium Nanoparticles (SeNPs) against Potentially Pathogenic Oral Microorganisms: A Scoping Review.

Biofilms are responsible for the most prevalent oral infections such as caries, periodontal disease, and pulp and periapical lesions, which affect the quality of life of people. Antibiotics have been widely used to treat these conditions as therapeutic and prophylactic compounds. However, due to the emergence of microbial resistance to antibiotics, there is an urgent need to develop and evaluate new antimicrobial agents. This scoping review offers an extensive and detailed synthesis of the potential role of selenium nanoparticles (SeNPs) in combating oral pathogens responsible for causing infectious diseases. A systematic search was conducted up until May 2022, encompassing the MEDLINE, Embase, Scopus, and Lilacs databases. We included studies focused on evaluating the antimicrobial efficacy of SeNPs on planktonic and biofilm forms and their side effects in in vitro studies. The selection process and data extraction were carried out by two researchers independently. A qualitative synthesis of the results was performed. A total of twenty-two articles were considered eligible for this scoping review. Most of the studies reported relevant antimicrobial efficacy against C. albicans, S. mutans, E. faecalis, and P. gingivalis, as well as effective antioxidant activity and limited toxicity. Further research is mandatory to critically assess the effectiveness of this alternative treatment in ex vivo and in vivo settings, with detailed information about SeNPs concentrations employed, their physicochemical properties, and the experimental conditions to provide enough evidence to address the construction and development of well-designed and safe protocols.