Virulence Factors and Antifungal Susceptibility in Candida Species Isolated from Dermatomycosis Patients.

Dermatomycoses caused by Candida spp. are increasingly common, however there are few reports in the literature regarding their epidemiology, pathogenesis and antifungal susceptibility of these fungal pathogens. This study aimed to identify, characterize virulence and determine the antifungal susceptibility of Candida species isolated from patients with dermatomycoses. We studied a total of 45 yeast samples isolated from dermal scrapings from patients treated at a public hospital, Bauru, São Paulo, Brazil. After identification, the samples were analyzed for protease activity, phospholipase, biofilm formation and antifungal susceptibility. The most common species was Candida albicans (40%), followed by C. krusei (22.22%), C. parapsilosis complex (22.22%) and C. famata (6.67%). Regarding virulence mechanisms, 57.78% and 28.89% of the samples showed enzymatic activity for protease and phospholipase, respectively. A total of 13.33% of the samples showed secretion of both enzymes. All isolates were biofilm producers, and a higher production was observed in C. tropicalis isolates. Regarding the antifungal susceptibility test, 97.78% of the samples had the highest levels of the minimal inhibitory concentration (MIC) for terbinafine, and one C. krusei sample showed intermediate susceptibility to fluconazole. The correct identification of dermatomycosis-related microorganisms, as well as a better knowledge of their pathogenicity and susceptibility against the antifungals used in the clinic, is extremely important for an efficient preventive and therapeutic action.

Virulence factors and antifungal susceptibility in candida species isolated from dermatomycosis patients

Dermatomycoses caused by Candida spp. are increasingly common, however there are few reports in the literature regarding their epidemiology, pathogenesis and antifungal susceptibility of these fungal pathogens. This study aimed to identify, characterize virulence and determine the antifungal susceptibility of Candida species isolated from patients with dermatomycoses. We studied a total of 45 yeast samples isolated from dermal scrapings from patients treated at a public hospital, Bauru, São Paulo, Brazil. After identification, the samples were analyzed for protease activity, phospholipase, biofilm formation and antifungal susceptibility. The most common species was Candida albicans (40%), followed by C. krusei (22.22%), C. parapsilosis complex (22.22%) and C. famata (6.67%). Regarding virulence mechanisms, 57.78% and 28.89% of the samples showed enzymatic activity for protease and phospholipase, respectively. A total of 13.33% of the samples showed secretion of both enzymes. All isolates were biofilm producers, and a higher production was observed in C. tropicalis isolates. Regarding the antifungal susceptibility test, 97.78% of the samples had the highest levels of the minimal inhibitory concentration (MIC) for terbinafine, and one C. krusei sample showed intermediate susceptibility to fluconazole. The correct identification of dermatomycosis-related microorganisms, as well as a better knowledge of their pathogenicity and susceptibility against the antifungals used in the clinic, is extremely important for an efficient preventive and therapeutic action(AU).

Prevalência e perfil de susceptibilidade a antimicrobianos dos uropatógenos em pacientes atendidos no Instituto Lauro de Souza Lima/Bauru/SP / Prevalence and antimicrobial susceptibility profile of uropathogens in patients treated at the Instituto Lauro de Souza Lima / Bauru / SP

As infecções de trato urinário (ITU) estão entre as doenças infecciosas mais comuns na prática clínica. O objetivo do presente estudo foi investigar a prevalência de microrganismos patogênicos, analisando a faixa etária e gênero mais acometidos bem como o perfil de resistência aos antimicrobianos. O estudo caracterizou-se por uma pesquisa histórica documental, na qual se analisou registros de 605 uroculturas realizadas pelo Laboratório de microbiologia do Instituto Lauro de Souza Lima, na cidade de Bauru/SP, no período de Outubro de 2010 a Outubro de 2015. Foram incluídos pacientes de ambos os gêneros e de todas as idades. Os dados foram coletados a partir do livro de registro de exames do laboratório e do sistema de informatização SIGH e transcritos para uma planilha eletrônica utilizando o programa Microsoft Office Excel. Das 605 uroculturas analisadas, 24,2% apresentaram resultados positivos para ITU. Dentre as positivas, 75,3% foram de pacientes do gênerofeminino. Analisando a incidência dos microrganismos, a bactéria Escherichia coli foi a mais isolada, apresentando maior resistência à Penicilina G, quinolonas e trimetoprim-sulfamatoxazol. Pode-se concluir que o correto diagnóstico é imprescindívelna escolha e na instituição da antibioticoterapia mais adequada, evitando o uso indiscriminado de antimicrobianos...

The neonatal immune system: immunomodulation of infections in early life.

The innate and adaptive immune responses in neonates are usually functionally impaired when compared with their adult counterparts. The qualitative and quantitative differences in the neonatal immune response put them at risk for the development of bacterial and viral infections, resulting in increased mortality. Newborns often exhibit decreased production of Th1-polarizing cytokines and are biased toward Th2-type responses. Studies aimed at understanding the plasticity of the immune response in the neonatal and early infant periods or that seek to improve neonatal innate immune function with adjuvants or special formulations are crucial for preventing the infectious disease burden in this susceptible group. Considerable studies focused on identifying potential immunomodulatory therapies have been performed in murine models. This article highlights the strategies used in the emerging field of immunomodulation in bacterial and viral pathogens, focusing on preclinical studies carried out in animal models with particular emphasis on neonatal-specific immune deficits.

Profile of autoantibodies against phosphorylcholine and cross-reactivity to oxidation-specific neoantigens in selective IgA deficiency with or without autoimmune diseases.

Immunoglobulin A deficiency (IgAD) is considered the most common form of primary immunodeficiency. The majority of IgA-deficient individuals are considered asymptomatic, even though IgAD has been associated with an increased frequency of recurrent infections, allergy, and autoimmune diseases. In this study we evaluate the Natural autoantibodies (NatAbs) reactivity to phosphorylcholine (PC) and to some pro-inflammatory molecules in IgAD with or without autoimmune disorders. We observed that in the absence of IgA there is an enhancement of IgG subclasses functioning as NatAbs against PC. Immunoglobulin G (IgG) against lipopolysaccharide, C-reactive protein, and IgA was found in IgAD, regardless of the autoimmune manifestations. Nonetheless, IgAD patients with autoimmune disease showed significantly higher IgG reactivity against pro-inflammatory molecules, such as cardiolipin, oxidized low-density lipoproteins, and phosphatidylserine, with positive correlation between them. In conclusion, the IgG NatAbs against PC may represent a compensatory defense mechanism against infections and control excess of inflammation, explaining the asymptomatic status in the IgA deficiency.

Immunization of neonatal mice with LAMP/p55 HIV gag DNA elicits robust immune responses that last to adulthood.

Successful T cell priming in early postnatal life that can generate effective long-lasting responses until adulthood is critical in HIV vaccination strategies because it prevents early sexual initiation and breastfeeding transmission of HIV. A chimeric DNA vaccine encoding p55 HIV gag associated with lysosome-associated membrane protein 1 (LAMP-1; which drives the antigen to the MIIC compartment), has been used to enhance cellular and humoral antigen-specific responses in adult mice and macaques. Herein, we investigated LAMP-1/gag vaccine immunogenicity in the neonatal period in mice and its ability to generate long-lasting effects. Neonatal vaccination with chimeric LAMP/gag generated stronger Gag-specific immune responses, as measured by the breadth of the Gag peptide-specific IFN-gamma, proliferative responsiveness, cytokine production and antibody production, all of which revealed activation of CD4+ T cells as well as the generation of a more robust CTL response compared to gag vaccine alone. To induce long-lived T and B cell memory responses, it was necessary to immunize neonates with the chimeric LAMP/gag DNA vaccine. The LAMP/gag DNA vaccine strategy could be particularly useful for generating an anti-HIV immune response in the early postnatal period capable of inducing long-term immunological memory.

Balance between early life tolerance and sensitization in allergy: dependence on the timing and intensity of prenatal and postnatal allergen exposure of the mother.

Allergens can be maternally transferred to the fetus or neonate, though it is uncertain how this initial allergen exposure may impact the development of allergy responses. To evaluate the roles of timing and level of maternal allergen exposure in the early life sensitization of progeny, female BALB/c mice were given ovalbumin (OVA) orally during pregnancy, lactation or weekly at each stage to investigate the immunoglobulin E (IgE) antibody production and cellular responsiveness of their offspring. Exposure to OVA during pregnancy was also evaluated in OVA-specific T-cell receptor (TCR) transgenic (DO11.10) mice. The effect of prenatal antigen exposure on offspring sensitization was dependent on antigen intake, with low-dose OVA inducing tolerance followed by neonatal immunization that was sustained even when pups were immunized when 3 weeks old. These offspring received high levels of transforming growth factor-beta via breastfeeding. High-dose exposure during the first week of pregnancy or perinatal period induced transient inhibition of IgE production following neonatal immunization; although for later immunization IgE production was enhanced in these offspring. Postnatal maternal antigen exposure provided OVA transference via breastfeeding, which consequently induced increased offspring susceptibility to IgE antibody production according to week post-birth. The effect of low-dose maternal exposure during pregnancy was further evaluated using OVA transgenic TCR dams as a model. These progeny presented pronounced entry of CD4(+) T cells into the S phase of the cell cycle with a skewed T helper type 2 response early in life, revealing the occurrence of allergen priming in utero. The balance between tolerance and sensitization depended on the amount and timing of maternal allergen intake during pregnancy.

Maternal immunization to modulate the development of allergic response and pathogen infections.

This article reviews recent experimental approaches of preventive strategies regarding allergy and infections by pathogens, particularly in early childhood, by targeting maternal immunomodulation. Basic research is essential to understand maternal vaccination as a strategy to control allergic disease and bacterial and viral infections; thus, providing support for future translational research. The environmental stimuli and host genetic factors, along with maternal influences in early life when immune systems are developing and during postnatal life, are essential for the decision between tolerance induction or allergen sensitization. Maternal immunomodulation strategies should serve as a challenge when attempting to halt the spread of allergy responses and viral infections, until the innate and adaptive arms of the immune system of the neonates are competent.

Long-term anergy in orally tolerized mice is linked to decreased B7.2 expression on B cells.

Durable antigen (Ag)-specific T- and B-cell anergy induced by oral tolerance is an attractive strategy for immunotherapy of allergic diseases. Here, we address the lasting effect of oral tolerance induction in naïve or primed mice to ovalbumin (OVA) on antibody production. Single feeding with OVA prior to immunization or double feeding, before and after Ag priming, in A/Sn mice, induced a long-lasting suppression of IgE, IgG1 and IgG2a responses up to 8 months after immunization. In contrast, primed-fed mice had transient IgE inhibition. Naive and double-treated mice showed marked Ag-specific unresponsiveness and scarce cytokines production. Inhibition of IL-2 and IFN-gamma secretion in naïve-fed mice were restored in the presence of anti-CD28 mAb plus Ag stimulation. The durable inhibition of Ab production in OVA-fed mice was related to the persistent decrease of B7.2 expression on B cells. Ag feeding in naive and primed status may be a prophylactic measure to avoid later Ag sensitization.

Preconception maternal immunization to dust mite inhibits the type I hypersensitivity response of offspring.

BACKGROUND: The maternal immunologic experience associated with early life exposure to allergens might contribute to the development of allergy during infancy. OBJECTIVES: We sought to analyze the effect of the mother's immunization before conception with the dust mite Dermatophagoides pteronyssinus on the allergen priming and hypersensitivity response in early immunized offspring. The kinetics of D pteronyssinus immunization were observed from newborn to adult age, and the secondary response to D pteronyssinus was followed in offspring immunized in early life. METHODS: Female A/Sn mice were immunized or not with D pteronyssinus and mated with male C57BL/6 mice. The hybrid offspring were immunized to investigate allotypes and subclasses of anti-D pteronyssinus antibody, as well as total IgE levels, by using ELISA and anti-D pteronyssinus IgE antibody by using the passive cutaneous anaphylaxis reaction. Ovalbumin was used for heterologous immunization. Cytokines were measured in the cell-culture supernatant by means of ELISA, and CD4(+)CD25(+) cells were analyzed by means of flow cytometry. RESULTS: Offspring from immune mothers have not shown evidence of prenatal or postnatal allergen priming with respect to humoral level. Immunization with D pteronyssinus of offspring at very early life and in the postweaning period inhibited anti-D pteronyssinus IgE and IgG1 antibody production, along with the expected presence of maternal antibody. Furthermore, offspring antibody responsiveness from immune mothers has remained quiescent on secondary allergenic challenge. This maternal influence on the offspring antibody response was specific to D pteronyssinus because the immunization with a heterologous antigen did not alter IgE response. Maternal D pteronyssinus immunization induced a significant decrease of the IFN-gamma level in the offspring, avoided an exacerbation of T(H)2 cytokine secretion, and, concomitantly, upregulated the number of CD4(+)CD25(+) T cells. CONCLUSION: Maternal immunization to D pteronyssinus seems to protect offspring from the development of allergy.