Biology subjects

Rodrigues, L. S.

Publications and source records attributed to Rodrigues, L. S..

5 recordsLinked to original sources

bioRxiv2024

Proteomic And Transcriptomic Host Biomarkers For Detection Of Pleural Tuberculosis

Current diagnosis of pleural tuberculosis (PLTB) is based on highly invasive procedures. Therefore, blood-based host biomarkers could represent a low-invasive diagnostic alternative. Plasma and pleural effusion, as well as blood-and pleural fluid mononuclear cells (PBMCs and PFMCs), were sampled from patients with PLTB and other pleural diseases (OPLDs). In pleural effusion, ApoA1, C1q, CRP, IL-6, IFN-{gamma}, IP-10, MIG, S100A12, SAA1/A2, and serpin-A3 were significantly higher in PLTB compared to OPLD, whereas only SAA1/A2 showed discriminatory potential in plasma. Increased mRNA levels were observed in PFMCs of PLTB for CD8A, GBP5, SLAMF7, CXCL10, IL2, GNLY, IL23A, PDCD1 and BCMA, whereas HMOX1, CD163, DUSP3, IGF1, GUSB and MARCO were decreased. In PBMCs of PLTB, only CCL22 expression was decreased. GBP5 was significantly higher expressed in PLTB for both cell types. This study shows the potential of transcriptomic and proteomic host biomarkers to differentiate PLTB from OPLDs also when applying low-invasive methods.

microbiology↗

bioRxiv2022

New broad-spectrum anti-Flavivirus human antibodies with Zika virus-neutralizing potential

Flavivirus infections show recurrent outbreaks and can be responsible for disease complications such as Hemorrhagic Dengue Fever and Congenital Zika Virus Syndrome. Effective therapeutic interventions are still a challenge. Antibodies can provide significant protection, although antibody response may fail due to ADE (Antibody-Dependent Enhancement) reactions or immune escape mutations. To generate effective neutralizing antibodies, the choice of the target antigen is a crucial part of the process. Human anti-Flavivirus antibodies were selected from a combinatorial library displayed on a phage surface. The antibodies were selected against a mimetic peptide based on the fusion loop region in Domain II of the protein E, which is highly conserved among different Flavivirus. Four rounds of selection were performed using the synthetic peptide in two strategies: the first was using acidic elution of bound phages, and the second was applying a competing procedure. After panning, the selected VH and VL domains were determined by combining NGS and bioinformatic approaches. Three different human monoclonal antibodies were expressed as scFvs and further characterized. All showed binding capacity to Zika (ZIKV), Yellow Fever (YFV), and Dengue (DENV) viruses. Two of these antibodies, AZ1p and AZ6m, could neutralize the ZIKV infection in a PRNT assay. These new antibodies have the potential to be used in therapeutic intervention against different Flavivirus illnesses and, due to the conservation of the fusion loop region, they may be resistant to scape mutations. Author summaryThe central idea of this work is to present a possible unique therapeutic approach to combat different diseases that cause health problems annually, such as Dengue and yellow fever infections and Zika congenital syndromes. The viruses that cause these diseases, of the Flavivirus genus, typically have disease amplification reactions and evasion mechanisms of the immune response that hinder the success of specific therapies and vaccines and require new forms of effective and safe treatments. We have developed new neutralizing human antibodies so that they bind to a highly conserved region of Flavivirus, called the fusion loop, and in such a way as to avoid adverse effects associated with anti-Flavivirus antibodies. We showed that the antibodies have high cross-reactivity against different Flaviviruses and we exemplified their neutralizing capacity for Zika virus infection in an ex vivo assay. New monoclonal antibodies such as those presented here may contribute to the control of important tropical diseases in a safer and more efficient way.

immunology↗

bioRxiv2020

Diversity of Antimicrobial-Resistant Aeromonas Species Isolated from Aquatic Environments in Brazil

In the present study, we characterized antimicrobial resistance profile and genetic relatedness of Aeromonas spp. isolated from healthcare and urban effluents, wastewater treatment plant (WWTP), and river water. We detected the presence of genes responsible for the resistance to {beta}-lactam, quinolone, and aminoglycoside. Enterobacterial Repetitive Intergenic Consensus PCR and multilocus sequence typing (MLST) were carried out to differentiate the strains and multilocus phylogenetic analysis (MLPA) was used to identify species. A total of 28 Aeromonas spp. cefotaxime-resistant strains were identified that carried a variety of resistance determinants, including uncommon GES-type {beta}-lactamases. Multidrug-resistant Aeromonas spp. were found in hospital wastewater, WWTP, and sanitary effluent. Among these isolates, we detected A. caviae producing GES-1 or GES-5, as well as A. veronii harboring GES-7 or GES-16. We successfully identified Aeromonas spp. by using MLPA and found that A. caviae was the most prevalent species (85.7%). In contrast, it was not possible to determine sequence type of all isolates, suggesting incompleteness of the Aeromonas spp. MLST database. Our findings reinforce the notion about the ability of Aeromonas spp. to acquire determinants of antimicrobial resistance from the environment. Such ability can be enhanced by the release of untreated healthcare effluents, in addition to the presence of antimicrobials, recognized as potential factors for the spread of resistance. Thus, Aeromonas spp. could be included as priority pathogens under the One Health concept. IMPORTANCEAeromonas species are native bacteria in aquatic ecosystems worldwide. However, they have also been isolated from humans and animals. Globally, aquatic environments have been affected by anthropogenic activities. For example, the excessive use of antimicrobials in medical and veterinary practice causes the development of bacterial resistance. In addition, eliminated hospital and sanitary effluents can also serve as potential sources of bacteria carrying antimicrobial resistance genes. Thereby, impacted environments play an important role in the transmission of these pathogens, their evolution, and dissemination of genes conferring resistance to antimicrobials. Aeromonas spp. have been reported as a reservoir of antimicrobial resistance genes in the environment. In this study, we identified a great repertoire of antimicrobial resistance genes in Aeromonas spp. from diverse aquatic ecosystems, including those that encode enzymes degrading broad-spectrum antimicrobials widely used to treat healthcare-associated infections. These are a public health threat as they may spread in the population.

microbiology↗

bioRxiv2019

HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome

Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS / MS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases. Here the expression of Endogenous retroviruses K and W (HERV-K and HERV-W) was determined in blood from moderately and severely affected ME/CFS patients. HERV-K was overexpressed only in moderately affected individuals and HERV-W showed no difference. This is the first report about HERV-K differential expression in moderate ME/CFS.

molecular biology↗

bioRxiv2019

The discriminant pattern of pleural fluid inflammatory mediators between tuberculosis and other causes of exudative pleural effusion

Pleural tuberculosis (PlTB), a form of extrapulmonary TB, remains as a challenge in the diagnosis among many causes of pleural effusion. We recently reported that the combinatorial analysis of interferon-gamma (IFN-{gamma}), IFN-{gamma}-inducible protein 10 (IP-10), and adenosine deaminase (ADA) from the pleural microenvironment was useful to distinguish pleural effusion caused by TB (microbiologically or not confirmed cases) among other etiologies. In this prospective cohort study, a set of inflammatory mediators was quantified in blood and pleural fluid (PF) from exudative pleural effusion cases, including PlTB (n = 22) and non-PlTB (NTB; n= 17) patients. The levels of IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-{gamma}, TNF, IP-10, TGF-{beta}1, and ADA were measured and a principal component analysis was applied in order to identify the mediators who contributed most for the variance in data. IFN-{gamma}, IP-10, TNF, TGF-{beta}, and ADA quantified in PF showed significantly higher concentrations in PlTB patients when compared to NTB ones. When blood and PF were compared, we have identified significantly higher concentrations of IL-6 and IL-10 in PF, in both groups. TGF-{beta}, solely, showed significantly increased levels in PF and blood from PlTB when both clinical specimens were compared to NTB patients. Principal components analysis from PF revealed that the ADA, IP-10, TGF-{beta}, and IFN-{gamma} contributed most for the discriminatory capacity between TPlB and NTB. Our findings showed that important inflammatory mediators in PF may discriminate TB cases from other causes of exudative effusion, the main diseases considered in the differential diagnosis of PlTB.

immunology↗