Browsing by Author "Gomes, João Paulo"
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- Accuracy of prenatal culture in predicting intrapartum group B streptococcus colonization statusPublication . Florindo, C.; Damião, V.; Lima, J.; Nogueira, I.; Rocha, I.; Caetano, P.; Ribeiro, L.; Viegas, S.; Gomes, João Paulo; Borrego, M.J.Objective: To evaluate the positive predictive value (PPV) of group B Streptococcus (GBS) cultures at 35–37 weeks of gestation relative to GBS colonization status at delivery. Methods: Rectovaginal swabs from 221 women at labor in four Lisbon hospitals were collected for GBS screening according to the CDC guidelines. Results: The PPV was 24.4%. IAP was administered to 100% of prenatally GBS positive women. There was no case of early onset GBS disease (EOD). Conclusions: Poor accuracy of prenatal cultures in identifying true candidates for IAP highlights the need for Portuguese clinical and laboratory guidelines to prevent EOD and antibiotic overtreatment of pregnant women.
- Adaptive evolution of the Chlamydia trachomatis dominant antigen reveals distinct evolutionary scenarios for B- and T-cell epitopes: worldwide surveyPublication . Nunes, A.; Nogueira, P.J.; Borrego, M.J.; Gomes, João PauloBackground: Chlamydia trachomatis is one of the most disseminated human pathogens, for which no vaccine is available yet. Understanding the impact of the host pressure on pathogen antigens is crucial, but so far it was only assessed for highly-restricted geographic areas. We aimed to evaluate the evolutionary picture of the chlamydial key antigen (MOMP), which is one of the leading multi-subunit vaccine candidates, in a worldwide basis. Methodology/Principal Findings: Using genetics, molecular evolution methods and mathematical modelling, we analyzed all MOMP sequences reported worldwide, composed by 5026 strains from 33 geographic regions of five continents. Overall, 35.9% of variants were detected. The evolutionary pattern of MOMP amino acid gains/losses was found to differ from the remaining chromosome, reflecting the demanding constraints of this porin, adhesin and dominant antigen. Amino acid changes were 4.3-fold more frequent in host-interacting domains (P,10212), specifically within B-cell epitopes (P,1025), where 25% of them are at fixation (P,1025). According to the typical pathogen-host arms race, this rampant B-cell antigenic variation likely represents neutralization escape mutants, as some mutations were previously shown to abrogate neutralization of chlamydial infectivity in vitro. In contrast, T-cell clusters of diverse HLA specificities are under purifying selection, suggesting a strategy that may lead to immune subversion. Moreover, several silent mutations are at fixation, generating preferential codons that may influence expression, and may also reflect recombination-derived ‘hitchhikingeffect’ from favourable nonsilent changes. Interestingly, the most prevalent C. trachomatis genotypes, E and F, showed a mutation rate 22.3-fold lower than that of the remainder (P,10220), suggesting more fitted antigenic profiles. Conclusions/Significance: Globally, the adaptive evolution of the C. trachomatis dominant antigen is likely driven by its complex pathogenesis-related function and reflects distinct evolutionary antigenic scenarios that may benefit the pathogen, and thus should be taking into account in the development of a MOMP-based vaccine.
- Allelic Diversity among Helicobacter pylori Outer Membrane Protein Genes homB and homA Generated by RecombinationPublication . Oleastro, Mónica; Cordeiro, Rita; Ménard, Armelle; Gomes, João PauloRecombination is one of the main mechanisms contributing to Helicobacter pylori genomic variability. homB and homA are paralogous genes coding for H. pylori outer membrane proteins (OMPs). Both genes display allelic variation yielded by polymorphisms of the genes’ middle regions, with six different alleles. This study used bioinformatic and statistical analyses to evaluate whether the allelic diversity of homB and homA is generated by recombination. A detailed molecular analysis of the most prevalent homB allelic variant was also performed to establish its molecular profile. The two most prevalent homB and homA allelic variants resulted from interallelic homologous recombination between the rarest allelic variants of each gene, with a crossover point localized in the middle of the genes, containing the allelic region. Molecular analysis of the most prevalent homB allele revealed a geographic partition among Western and East Asian strains, more noticeable for the 5 and 3 homB regions than for the middle allelic regions. In conclusion, the diversity of the 5 and 3 homB regions reflect the strains’ geographical origin, and variants likely occur via the accumulation of single nucleotide polymorphisms. On the other hand, homologous recombination seems to play an important role in the diversification of the highly polymorphic homB and homA allele-defining regions, where the most prevalent alleles worldwide result from genomic exchange between the rarest variants of each gene, suggesting that the resulting combinations confer biological advantages to H. pylori. This phenomenon illustrates an evolutionary scenario in which recombination appears to be associated with ecological success.
- An Overview of Monkeypox Virus Detection in Different Clinical Samples and Analysis of Temporal Viral Load DynamicsPublication . Cordeiro, Rita; Pelerito, Ana; de Carvalho, Isabel Lopes; Lopo, Sílvia; Neves, Raquel; Rocha, Raquel; Palminha, Paula; Verdasca, Nuno; Palhinhas, Cláudia; Borrego, Maria José; Manita, Carla; Ferreira, Idalina; Bettencourt, Célia; Vieira, Patrícia; Silva, Sónia; Água-Doce, Ivone; Roque, Carla; Cordeiro, Dora; Brondani, Greice; Santos, João Almeida; Martins, Susana; Rodrigues, Irene; Ribeiro, Carlos; Núncio, Maria Sofia; Gomes, João Paulo; Batista, Fernando da ConceiçãoMpox is a zoonotic disease caused by the Monkeypox virus (MPXV), and since May 2022, tens of thousands of cases have been reported in non-endemic countries. We aimed to evaluate the suitability of different sample types for mpox diagnostic and assess the temporal dynamics of viral load. We evaluated 1914 samples from 953 laboratory-confirmed cases. The positivity rate was higher for lesion (91.3%) and rectal swabs (86.1%) when compared with oropharyngeal swabs (69.5%) and urines (41.2%), indicating higher viral loads for the former. Supporting this, lesion and rectal swabs showed lower median PCR C values (C = 23 and C = 24), compared to oropharyngeal swabs and urines (C = 31). Stable MPXV loads were observed in swabs from lesions up to 30 days after symptoms onset, contrasting with a considerable decrease in viral load in rectal and oropharyngeal swabs. Overall, these results point to lesion swabs as the most suitable samples for detecting MPXV in the 2022-2023 multicountry outbreak and show comparable accuracy to rectal swabs up to 8 days after symptoms onset. These findings, together with the observation that about 5% of patients were diagnosed through oropharyngeal swabs while having negative lesions, suggest that multisite testing should be performed to increase diagnostic sensitivity.
- Animal-to-human transmission of Mycobacterium pinnipediiPublication . Macedo, Rita; Isidro, Joana; Gomes, Maria Conceição; Botelho, Ana; Albuquerque, Teresa; Sogorb, Arlete; Bernardino, Rui; Fernandes, Teresa Lobo; Mourato, Teresa; Durval, Mário; Gomes, João PauloExtract: Mycobacterium pinnipedii, the known causative agent of tuberculosis (TB) in marine mammals, was only recognised as a member of the Mycobacterium tuberculosis complex in 2003 [1] and is believed to cause TB in several species, including nonmarine mammals [2, 3] and even humans [4]. The assumption of zoonotic transmission has been strongly reinforced by a disruptive study published in 2014 by a team of archaeologists from Tübingen, Germany [5]. Based on archaeological and genomic investigations on millennial human skeletons, the authors implicated sea mammals infected with M. pinnipedii as a source of New World human TB. Considering that this phenomenon pre-dates the human migrations to South America by several centuries, they refuted the previous scientific hypothesis of TB driven by human contact [6].
- Antimicrobial Resistance and Biofilms Underlying Catheter-Related Bloodstream Coinfection by Enterobacter cloacae Complex and Candida parapsilosisPublication . Štefánek, Matúš; Wenner, Sigurd; Borges, Vítor; Pinto, Miguel; Gomes, João Paulo; Rodrigues, João; Faria, Isabel; Pessanha, Maria Ana; Martins, Filomena; Sabino, Raquel; Veríssimo, Cristina; Nogueira, Isabel D.; Carvalho, Patrícia Almeida; Bujdáková, Helena; Jordao, LuisaBiofilm-associated infections are a public health concern especially in the context of healthcare-associated infections such as catheter-related bloodstream infections (CRBSIs). We evaluated the biofilm formation and antimicrobials resistance (AMR) of Enterobacter cloacae complex and Candida parapsilosis co-isolated from a CRBSI patient. Antimicrobial susceptibility of central venous catheters (CVCs) and hemoculture (HC) isolates was evaluated, including whole genome sequencing (WGS) resistome analysis and evaluation of gene expression to obtain insight into their AMR determinants. Crystal violet assay was used to assess dual biofilm biomass and microscopy was used to elucidate a microorganism’s distribution within biofilms assembled on different materials. Bacteria were multidrug-resistant including resistance to colistin and beta-lactams, likely linked to the mcr-9-like phosphoethanolamine transferase and to an ACT family cephalosporin-hydrolyzing class C beta-lactamase, respectively. The R398I and Y132F mutations in the ERG11 gene and its differential expression might account for C. parapsilosis resistance to fluconazole. The phenotype of dual biofilms assembled on glass, polystyrene and polyurethane depends on the material and how biofilms were initiated by one or both pathogens. Biofilms assembled on polyurethane were denser and richer in the extracellular polymeric matrix, and microorganisms were differently distributed on the inner/outer surface of the CVC.
- APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016Publication . O’Toole, Áine; Neher, Richard A.; Ndodo, Nnaemeka; Borges, Vitor; Gannon, Ben; Gomes, João Paulo; Groves, Natalie; King, David J.; Maloney, Daniel; Lemey, Philippe; Lewandowski, Kuiama; Loman, Nicholas; Myers, Richard; Omah, Ifeanyi F.; Suchard, Marc A.; Worobey, Michael; Chand, Meera; Ihekweazu, Chikwe; Ulaeto, David; Adetifa, Ifedayo; Rambaut, AndrewHistorically, mpox has been characterized as an endemic zoonotic disease that transmits through contact with the reservoir rodent host in West and Central Africa. However, in May 2022, human cases of mpox were detected spreading internationally beyond countries with known endemic reservoirs. When the first cases from 2022 were sequenced, they shared 42 nucleotide differences from the closest mpox virus (MPXV) previously sampled. Nearly all these mutations are characteristic of the action of APOBEC3 deaminases, host enzymes with antiviral function. Assuming APOBEC3 editing is characteristic of human MPXV infection, we developed a dual-process phylogenetic molecular clock that-inferring a rate of ~6 APOBEC3 mutations per year-estimates that MPXV has been circulating in humans since 2016. These observations of sustained MPXV transmission present a fundamental shift to the perceived paradigm of MPXV epidemiology as a zoonosis and highlight the need for revising public health messaging around MPXV as well as outbreak management and control.
- Application of Next-Generation Sequencing (NGS) to the study of infectious diseasesPublication . Gomes, João Paulo
- Are Food Producing animals a source of multidrug-resistant E. coli and Salmonella spp.?Publication . Pista, Angela; Silveira, Leonor; Gonçalves, Carlota; Costa, Sara; Carolino, Catarina; Santo, Bianca; Rosa, Rute; Penteado, Margarida; Alves, Margarida; Belas, Adriana; Santos, Isabel; Lima, Ana; Mota, Joana; Pedroso, Laurentina; Gomes, João Paulo; Nunes, Alexandra; Ramos, SóniaObjectives: To assess the role of food-producing animals as potential transmission vehicles of Salmonella spp. and E. coli to Humans, in order to understand the epidemiology and population structure of these zoonotic agents in Portugal.
- Assessment of the Transmission Dynamics of Clostridioides difficile in a Farm Environment Reveals the Presence of a New Toxigenic Strain Connected to Swine ProductionPublication . Alves, Frederico; Nunes, Alexandra; Castro, Rita; Sequeira, António; Moreira, Olga; Matias, Rui; Rodrigues, João Carlos; Silveira, Leonor; Gomes, João Paulo; Oleastro, MónicaThe recent increase in community-acquired Clostridioides difficile infections discloses the shift in this bacterium epidemiology. This study aimed at establishing a transmission network involving One Health components, as well as assessing the zoonotic potential and genomic features of dominant clones. Samples were collected from different compartments of animal, human and environmental origin, from an animal production unit. C. difficile isolates were characterized for toxigenic profile by multiplex-PCR, while genetic diversity was evaluated by PCR-ribotyping and whole genome-based analysis. The overall C. difficile prevalence was 37.2% (70/188), and included samples from environmental (58.3%, 35/60) and animal (31.5%, 35/111) compartments; human samples (n = 17) taken from healthy workers were negative. A predominant clone from RT033 was found in almost 90% of the positive samples, including samples from all compartments connected to the pig production unit, with core-genome single nucleotide variant (SNV)-based Analysis supporting a clonal transmission between them (mean distance of 0.1 ± 0.1 core-SNVs). The isolates from this clone (herein designated PT RT033) were positive for all C. difficile toxin genes (tcdA, tcdB, cdtA/cdtB). The phyloGenetic positioning of this clone was clearly distinct from the classical RT033 cluster, suggesting a different evolutionary route. This new clone shares genomic features with several RTs from the clade 5 Sequence Type (ST) 11, including a complete pathogenicity locus (PaLoc) that is more similar to the one found in toxigenic strains and contrasting to the less virulent classical RT033 (tcdA-, tcdB-, cdtA + /cdtB +). The presence of a tcdA gene truncated into two ORFs, not previously described, requires further evaluation concerning toxin functionality. We hypothesize that the unique combination of genetic elements found in the PT RT033 clone may contribute to host tropism and environmental dissemination and maintenance. This study constitutes the first report of a toxigenic RT033 clone and adds to the overall knowledge on Clade 5 sequence type 11, considered the C. difficile evolutionary lineage with the highest zoonotic potential. The presence of this clone in all compartments associated with the pig production unit suggests a transmission chain involving these animals and contributes to unveil the role played by animal and environmental reservoirs in this pathogen epidemiology.