Biology subjects

Epiphanio, S.

Publications and source records attributed to Epiphanio, S..

4 recordsLinked to original sources

bioRxiv2018

Natural avirulent Shigella boydii strain in the Brazilian Amazon lacks major virulence genes and present Type II, Type III and Type VI Secretion Systems

BackgroundAmong Shigella species, Shigella boydii has always displayed a smaller role to the overall Shigella burden, frequently placed at third in epidemiological studies and described as restricted to Southeast Asia. Here we characterize an S. boydii isolated from an epidemiological study enrolling 1,339 Brazilian children from the Amazon region, in which Shigella species solely was the fourth cause of bacterial diarrhea. S. boydii strain 183 was isolated from rotavirus co-infected children with acute diarrhea. Here we aimed to characterize this strain regarding virulence and, immune response in a pulmonary model.\n\nMethodsAn in vitro HEp-2 epithelial cell invasion assay was used to compare the invasive phenotype of S. boydii strain 183 with clinical and highly virulent S. flexneri strain, both isolated from Brazilian children. A murine pulmonary model was performed to assess lung damage by histopathological analysis. mRNA expression of immune response key genes was retrieved by multiplex real-time PCR and correlations were obtained by network analysis. Broad genome analysis was performed to confirm S. boydii identity and define its virulence profile.\n\nResultsS. boydii strain 183 showed fewer invasion rates in vitro and tissue damage in vivo as compared to virulent S. flexneri 201. When compared to a survival challenge in mice, S. boydii had 100% survival against 10% of virulent S. flexneri. Overall, mRNA immune gene expression suggests a protective response against S. boydii strains 183, in contrast to the inflammatory response induced by the virulent S. flexneri strain 201. Network analysis with S. boydii strain 183 displayed IFN-{gamma} protagonism, contrasting with the correlations centralized on TNF- by the virulent S. flexneri strain 201. The genome showed a lack of effector proteins and enterotoxins in S. boydii strain 183, and sequencing analysis of Ipa invasins revealed mutations at functional sites. This avirulent S. boydii strain 183 presents the Type II Secretion System, T6SS, in addition to T3SS.\n\nConclusionsIn addition to causing no disease, S. boydii strain 183 lacks effector proteins and enterotoxins. The presence of T6SS additional secretion system could provide an advantage to establish this strain among commensal bacteria.\n\nAUTHOR SUMMARYThe Shigella genus is a human pathogen responsible to shigellosis and remains one of the significant causes of morbidity and mortality in children under five years old. This genus has four species, Shigella flexneri, Shigella sonnei, Shigella boydii, and Shigella dysenteriae. S. flexneri and S. sonnei are the most common in the worldwide infections; S. dysenteriae is rarely found, and S. boydii is responsible for 1% of the infections and is known to be restricted to Southeast Asia. Once S. boydii have a relatively small role in global Shigella disease, there are few studies regarding its virulence and mechanisms. Here we characterize an S. boydii isolated from Brazilian children from the Amazon region, and aimed to describe this strain regarding virulence. It is known that Shigella species use the Type 3 Secretion System (T3SS) to invade and colonize the human intestine. We found in S. boydii the presence of Type 2 Secretion System (T2SS), Type 6 Secretion System (T6SS), in addition to the T3SS. The T6SS have been described in S. sonnei only, granting a competitive advantage against S. flexneri mixed cultures. The presence of T6SS additional secretion system could provide a benefit to establish this strain among commensal bacteria.

microbiology↗

bioRxiv2018

Critical contribution of endothelial protein C receptor in experimental malaria-associated acute respiratory distress syndrome

The severity of Plasmodium falciparum malaria is associated with parasite cytoadherence, but there is limited knowledge about the effect of parasite cytoadherence in malaria-associated acute respiratory distress syndrome (ARDS). Our objective was to evaluate the cytoadherence of infected red blood cells (iRBCs) in a murine model of ARDS and to appraise a potential function of endothelial protein C receptor (EPCR) in ARDS pathogenesis. DBA/2 mice infected with P. berghei ANKA were classified as ARDS- or hyperparasitemia (HP)-developing mice according to respiratory parameters and parasitemia. Lungs, blood and bronchoalveolar lavage were collected for gene expression or protein analyses. Primary cultures of microvascular lung endothelial cells from DBA/2 mice were analyzed for iRBC interactions. Lungs from ARDS-developing mice showed evidence of iRBC accumulation along with an increase in EPCR and TNF concentrations. Furthermore, TNF increased iRBC adherence in vitro. Dexamethasone-treated infected mice showed low levels of TNF and EPCR mRNA expression and, finally, decreased vascular permeability, thus protecting mice from ARDS. In conclusion, we identified that increased iRBC cytoadherence in the lungs underlies malaria-associated ARDS in DBA/2-infected mice and that inflammation increased cytoadherence capacity, suggesting a participation of EPCR and a conceivable target for drug development.

pathology↗

bioRxiv2018

Malaria during pregnancy and newborns outcome in an unstable transmission area in Brazil: a population-based record linkage study

BackgroundMalaria during pregnancy is one of the major causes of mortality in tropical regions, causing maternal anemia, intrauterine growth retardation, preterm birth, and low birth weight (LBW). The integration of the information systems is crucial to assess the dimension of gestational malaria in a wide and useful way, to improve decision making and maternal-child health.\n\nMethods and FindingsAn observational population-based study acquired information retrospectively from all live births that occurred between 2006 and 2014 in Cruzeiro do Sul (Acre, Brazil). Social and clinical data of the mother and newborn was extracted from the Information System of Live Births. Malaria episodes information was obtained from the Brazilian Epidemiological Surveillance Information System Malaria. A deterministic record linkage was performed to assess malaria impact on pregnancy. The studied population presented a malaria incidence of 8.9%, of which 63.9% infected by Plasmodium (P.) vivax. Reduction of newborns birth weight at term (small for gestational age (SGA) and LBW) has been found associated with P. vivax infection during pregnancy (SGA - OR 1.24, 95% CI 1.02-1.52, p=0.035; term LBW - OR 1.39, 95% CI 1.03-1.88, p=0.033). Additionally, P. falciparum infection during pregnancy has been found to be associated with preterm births (OR 1.54, 95% CI 1.09-2.18, p=0.016), which is related with late preterm births (OR 1.59, 95% CI 1.11-2.27, p=0.011).\n\nConclusionsDespite the decrease of malaria cases during the evaluated period, we present evidence of the deleterious effects of gestational malaria in a low transmission area in the Amazonian region. Regardless of Plasmodium species, malaria during pregnancy poses a risk for newborns birth weight reduction, highlighting the impact that P. vivax has on the fetus.\n\nFundingSao Paulo Research Foundation - FAPESP/Brazil.

epidemiology↗

bioRxiv2017

Plasmodium falciparum infection during pregnancy impairs fetal head growth: prospective and populational-based retrospective studies

BackgroundMalaria in pregnancy is associated with adverse effects on the fetus and newborns. However, the outcome on a newborns head circumference (HC) is still unclear. Here, we show the relation of malaria during pregnancy with fetal head growth.\n\nMethodsClinical and anthropometric data were collected from babies in two cohort studies of malaria-infected and non-infected pregnant women, in the Brazilian Amazon. One enrolled prospectively (PCS, Jan. 2013 to April 2015) through volunteer sampling, and followed until delivery, 600 malaria-infected and non-infected pregnant women. The other assembled retrospectively (RCS, Jan. 2012 to Dec. 2013) clinical and malaria data from 4697 pregnant women selected through population-based sampling. The effects of malaria during pregnancy in the newborns were assessed using a multivariate logistic regression. According with World Health Organization guidelines babies were classified in small head (HC < 1 SD below the median) and microcephaly (HC < 2 SD below the median) using international HC standards.\n\nResultsAnalysis of 251 (PCS) and 232 (RCS) malaria-infected, and 158 (PCS) and 3650 (RCS) non-infected women with clinical data and anthropometric measures of their babies was performed. Among the newborns, 70 (17.1%) in the PCS and 934 (24.1%) in the RCS presented with a small head (SH). Of these, 15 (3.7%) and 161 (4.2%), respectively, showed microcephaly (MC). The prevalence of newborns with a SH (30.7% in PCS and 36.6% in RCS) and MC (8.1% in PCS and 7.3% in RCS) was higher among babies born from women infected with Plasmodium falciparum during pregnancy. Multivariate logistic regression analyses revealed that P. falciparum infection during pregnancy represents a significant increased odds for the occurrence of a SH in newborns (PCS: OR 3.15, 95% CI 1.52-6.53, p=0.002; RCS: OR 1.91, 95% CI 1.21-3.04, p=0.006). Similarly, there is an increased odds of MC in babies born from mothers that were P. falciparum-infected (PCS: OR 5.09, 95% CI 1.12-23.17, p=0.035). Moreover, characterization of placental pathology corroborates the association analysis, particularly through the occurrence of more syncytial nuclear aggregates and inflammatory infiltrates in placentas from babies with the reduced head circumference.\n\nConclusionsThis work indicates that falciparum-malaria during pregnancy presents an increased likelihood of occurring reduction of head circumference in newborns, which is associated with placental malaria.\n\nTrial Registrationregistered as RBR-3yrqfq in the Brazilian Clinical Trials Registry

epidemiology↗