RESUMO
Candida auris is an emerging Candida sp. that has rapidly spread all over the world. The evidence regarding its origin and emerging resistance is still unclear. The severe infection caused by this species results in significant mortality and morbidity among the elderly and immunocompromised individuals. The development of drug resistance is the major factor associated with the therapeutic failure of existing antifungal agents. Previous studies have addressed the antifungal resistance profile and drug discovery for C. auris. However, complete coverage of this information in a single investigation is not yet available. In this review, we have mainly focused on recent developments in therapeutic strategies against C. auris. Based on the available information, several different approaches were discussed, including existing antifungal drugs, chemical compounds, essential oils, natural products, antifungal peptides, immunotherapy, antimicrobial photodynamic therapy, drug repurposing, and drug delivery systems. Among them, synthetic chemicals, natural products, and antifungal peptides are the prime contributors. However, a limited number of resources are available to prove the efficiency of these potential therapies in clinical usage. Therefore, we anticipate that the findings gathered in this review will encourage further in vivo studies and clinical trials.
RESUMO
Candida albicans can cause various types of oral infections, mainly associated with denture stomatitis. Conventional therapy has been linked to high recurrence, toxicity, and fungal resistance, necessitating the search for new drugs and delivery systems. In this study, caffeic acid phenethyl ester (CAPE) and gellan gum (GG) were studied as an antifungal agent and carrier system, respectively. First, we observed that different GG formulations (0.6 to 1.0% wt/vol) were able to incorporate and release CAPE, reaching a controlled and prolonged release over 180 min at 1.0% of GG. CAPE-GG formulations exhibited antifungal activity at CAPE concentrations ranging from 128 to >512 µg/mL. Furthermore, CAPE-GG formulations significantly decreased the fungal viability of C. albicans biofilms at short times (12 h), mainly at 1.0% of GG (p < 0.001). C. albicans protease activity was also reduced after 12 h of treatment with CAPE-GG formulations (p < 0.001). Importantly, CAPE was not cytotoxic to human keratinocytes, and CAPE-GG formulations at 1.0% decreased the fungal burden (p = 0.0087) and suppressed inflammation in a rat model of denture stomatitis. Altogether, these results indicate that GG is a promising delivery system for CAPE, showing effective activity against C. albicans and potential to be used in the treatment of denture stomatitis.
RESUMO
Acinetobacter baumannii is a multi-drug resistant microorganism. The objective of this study was to evaluate the antimicrobial and antibiofilm action of the pomegranate natural extract against eight strains of multidrug resistant Acinetobacter baumanii and to assess the extract cytotoxicity in a culture of Human Keratinocytes (HaCat). Broth microdilution method was used to determine the minimum inhibitory and minimum microbicidal concentrations of the extracts. The extract antibiofilm action was analysed by the MTT colorimetric test. The cytotoxicity evaluation was performed by the MTT colorimetric test, which analysed the mitochondrial cellular action, after contact of the extract for 5 min. The results were statistically analysed by ANOVA and Tukey test with a significance level α≤ 0.05. Punica granatum L. (pomegranate) extract had antimicrobial action on all the 8 clinical strains of Acinetobacter baumannii evaluated. The extract showed a significant reduction in metabolic action in biofilm for all the strains, with results statistically different from growth control (p≤0.05%). P. granatum extract applied for 5 min on human keratinocytes (HaCat) promoted cell viability in all the tested concentrations. The pomegranate extract is effective in reducing the multidrug-resistant clinical strains of Acinetobacter baumanni and is biocompatible. (AU)
Acinetobacter baumannii é um microrganismo multirresistente. O objetivo deste estudo foi avaliar a ação antimicrobiana e antibiofilme do extrato natural de romã contra oito cepas de A. baumanii multirresistente e avaliar a citotoxicidade do extrato em uma cultura de queratinócitos humanos (HaCat). O método de microdiluição em caldo foi utilizado para determinar as concentrações inibitórias mínimas e microbicidas mínimas dos extratos. A ação antibiofilme do extrato foi analisada pelo teste colorimétrico MTT. A avaliação da citotoxicidade foi realizada pelo teste colorimétrico MTT, que analisou a ação celular mitocondrial, após contato do extrato por 5 min. Os resultados foram analisados ââestatisticamente por ANOVA e teste de Tukey com nível de significância α≤ 0,05. O extrato de Punica granatum L. (romã) apresentou ação antimicrobiana em todas as 8 cepas clínicas avaliadas de A. baumannii. O extrato apresentou redução significativa na ação metabólica no biofilme para todas as linhagens, com resultados estatisticamente diferentes do controle de crescimento (p≤0,05%). O extrato de P. granatum aplicado por 5 min em queratinócitos humanos (HaCat) promoveu viabilidade celular em todas as concentrações testadas. O extrato de romã é eficaz na redução das cepas clínicas multirresistentes de Acinetobacter baumanni e é biocompatível. (AU)
RESUMO
Com a crescente resistência antibacteriana e fúngica, é evidente a necessidade de desenvolvimento de novos agentes antimicrobianos contra microrganismos de interesse médico-odontológico capazes de provocar infecções graves. Os óleos essenciais (OEs) vêm ganhando notoriedade na comunidade científica por apresentarem diversos benefícios, como atividade antimicrobiana e anti-inflamatória. Desta forma, o objetivo deste estudo é avaliar a atividade antimicrobiana dos OEs de Pelargonium graveolens (gerânio) e Cymbopogon schoenanthus (lemongrass), de forma isolada e combinada, sobre cepas de Streptococcus mutans, Staphylococcus aureus, Candida albicans, Candida dubliniensis e Candida krusei. Para isso, os valores da Concentração Microbicida Mínima (CMM) foram determinados pelo método de microdiluição em caldo preconizado pelo Clinical and Laboratory Standards Institute (CLSI), norma M27-A2 (Candida spp.) e M7-A6 (S. mutans e S. aureus). Já os efeitos combinados dos OEs foram avaliados pela técnica checkerboard. Para a mensuração da atividade antibiofilme foi utilizado o ensaio colorimétrico de MTT, evidenciando a atividade metabólica dos microrganismos, após 5 min e 24 h de contato com os OEs. Os dados obtidos nos testes in vitro obtiveram distribuição normal e foram analisados estatisticamente pelo método ANOVA complementado pelo Teste de Tukey (5%). Os resultados obtidos demonstraram que os OEs testados apresentaram atividade antimicrobiana sobre todas as cepas com valores de CMM variando entre 16 e 0,03%, sendo as cepas fúngicas as mais sensíveis ao tratamento. Quando combinados, os OEs apresentaram efeito aditivo ou sinérgico contra S. aureus. Em relação aos biofilmes monotípicos, ambos os OEs reduziram significativamente a formação de biofilme. Em geral, o tratamento por 24 h apresentou maior eficácia do que o tratamento de 5 min para a maioria dos microrganismos. Quando os OEs foram testados de forma combinada, estes promoveram redução do biofilme de S. aureus de até 27,3% no tratamento de 5 min e de até 93,3% no tratamento de 24 h. Concluiu-se que os OEs de gerânio e lemongrass apresentaram atividade antimicrobiana e antifúngica em cultura planctônica e em biofilmes monotípicos de S. aureus, S. mutans, C. albicans, C. dubliniensis e C. krusei apresentando potencial para serem utilizados para tratamento de infecções causadas por esses patógenos.
With the increasing antibacterial and fungal resistance, the development of new antimicrobial agents against microorganisms of medical and dental interest capable of causing severe infections are required. Essential oils (EOs) have been gaining notoriety in the scientific community for their therapeutic benefits, such as antimicrobial and anti-inflammatory activity. Thus, this study aimed to evaluate the antimicrobial activity of the EOs of Pelargonium graveolens (geranium) and Cymbopogon schoenanthus (lemongrass) in an isolated and combined form, against Streptococcus mutans, Staphylococcus aureus, Candida albicans, Candida dubliniensis and Candida krusei. For this, Minimum Microbicidal Concentration (CMM) values were determined by broth microdilution method recommended by the Clinical and Laboratory Standards Institute (CLSI), standard M27-A2 (Candida spp.) and M7-A6 (S. mutans and S. aureus). The combined effects of the EOs were evaluated using the checkerboard technique. To measure the antibiofilm activity, the MTT colorimetric assay was performed, showing the metabolic activity of the microorganisms, after 5 min and 24 h of contact with the EO. The data obtained in the in vitro tests presented normal distribution and were analyzed statistically by ANOVA and complemented by the Tukey method (5%). CMM results varied between 16 and 0,03%, with fungal strains being the most susceptible. The combined treatment with EOs presented additive and synergistic effects against S. aureus. Concerning monotypic biofilms, both EOs significantly reduced biofilm formation. Overall, 24 h treatment presented better effectiveness than 5 min treatment for most microorganisms. When the EOs were tested in combination, they promoted the reduction of S. aureus biofilm by up to 27,3% in the 5 min treatment and 93,3% in the 24 h treatment. Hence, the tested agents showed antimicrobial and antifungal activity in planktonic culture and in monotypic biofilms of S. aureus, S. mutans, C. albicans, C. dubliniensis and C. krusei, Thus, EOs of geranium and lemongrass has potential as an alternative for the treatment of infectious diseases caused by these pathogens.
