Browsing by Author "Borges, Vitor"
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- 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.
- Chlamydia trachomatis outbreak: when the virulence-associated genome backbone imports a prevalence-associated major antigen signaturePublication . Borges, Vitor; Cordeiro, Dora; Salas, Ana Isabel; Lodhia, Zohra; Correia, Cristina; Isidro, Joana; Fernandes, Cândida; Rodrigues, Ana; Azevedo, Jacinta; Alves, João; Rôxo, João; Rocha, Miguel; Corte-Real, Rita; Vieira, Luís; Borrego, Maria José; Gomes, João PauloChlamydia trachomatis is the most prevalent sexually transmitted bacterium worldwide and the causative agent of trachoma. Its strains are classified according to their ompA genotypes, which are strongly linked to differential tissue tropism and disease outcomes [ocular disease, urogenital disease and lymphogranuloma venereum (LGV)]. While the genome-based species phylogenetic tree presents four main clades correlating with tropism/prevalence, namely ocular, LGV, urogenital T1 (more prevalent genotypes) and urogenital T2 (less prevalent genotypes), inter-clade exchange of ompA is considered a rare phenomenon probably mediating marked tropism alterations. An LGV epidemic, associated with the clonal expansion of the L2b genotype, has emerged in the last few decades, raising concerns particularly due to its atypical clinical presentation (ulcerative proctitis) and circulation among men who have sex with men (MSM).
- Directional Evolution of Chlamydia trachomatis towards Niche-Specific AdaptationPublication . Borges, Vitor; Nunes, Alexandra; Ferreira, Rita; Borrego, Maria José; Gomes, João PauloOn behalf of the host-pathogen "arms race," a cutting-edge approach for elucidating genotype-phenotype relationships relies on the identification of positively selected loci involved in pathoadaptation. We studied the obligate intracellular bacterium Chlamydia trachomatis, for which same-species strains display a nearly identical core and pan genome, while presenting a wide range of tissue tropism and ecological success. We sought to evaluate the evolutionary patterns underlying species separation (divergence) and C. trachomatis serovar radiation (polymorphism) and to establish genotype-phenotype associations. By analyzing 60 Chlamydia strains, we detected traces of Muller's ratchet as a result of speciation and identified positively selected genes and codons hypothetically involved in the infection of different human cell types (e.g., columnar epithelial cells of ocular or genital mucosae and mononuclear phagocytes) and also events likely driving pathogenic and ecological success dissimilarities. In general, these genes code for proteins involved in immune response elicitation, proteolysis, and the subversion of host-cell functions, and also for proteins with unknown function(s). Several genes are potentially involved in more than one adaptive process, suggesting multiple functions or a distinct modus operandi for a specific function, and thus should be considered as crucial research targets. In addition, six of the nine genes encoding the putative antigen/adhesin polymorphic membrane proteins seem to be under positive selection along specific serovars, which sustains an essential biological role of this extra-large paralogue family in chlamydial pathobiology. This study provides insight into how evolutionary inferences illuminate ecological processes such as adaptation to different niches, pathogenicity, or ecological success driven by arms races.
- Effectiveness of COVID-19 vaccines administered in the 2023 autumnal campaigns in Europe: Results from the VEBIS primary care test-negative design study, September 2023–January 2024Publication . Laniece Delaunay, Charlotte; Melo, Aryse; Maurel, Marine; Mazagatos, Clara; Goerlitz, Luise; O’Donnell, Joan; Oroszi, Beatrix; Sève, Noémie; Rodrigues, Ana Paula; Martínez-Baz, Iván; Meijer, Adam; Mlinarić, Ivan; Latorre-Margalef, Neus; Lazăr, Mihaela; Pérez-Gimeno, Gloria; Dürrwald, Ralf; Bennett, Charlene; Túri, Gergő; Rameix-Welti, Marie-Anne; Guiomar, Raquel; Castilla, Jesús; Hooiveld, Mariëtte; Kurečić Filipović, Sanja; Samuelsson Hagey, Tove; Dijkstra, Frederika; Borges, Vitor; Ramos Marín, Violeta; Bacci, Sabrina; Kaczmarek, Marlena; Kissling, Esther; European primary care VE groupIn autumn 2023, European vaccination campaigns predominantly administered XBB.1.5 vaccine. In a European multicentre study, we estimated 2023 COVID-19 vaccine effectiveness (VE) against laboratory-confirmed symptomatic infection at primary care level between September 2023 and January 2024. Using a testnegative case–control design, we estimated VE in the target group for COVID-19 vaccination overall and by time since vaccination. We included 1057 cases and 4397 controls. Vaccine effectiveness was 40 % (95 % CI: 26–53 %) overall, 48 % (95 % CI: 31–61 %) among those vaccinated < 6 weeks of onset and 29 % (95 % CI: 3–49 %) at 6–14 weeks. Our results suggest that COVID-19 vaccines administered to target groups during the autumn 2023 campaigns showed clinically significant effectiveness against laboratory-confirmed, medically attended symptomatic SARS-CoV-2 infection in the 3 months following vaccination. A longer study period will allow for further variant-specific COVID-19 VE estimates, better understanding decline in VE and informing booster administration policies.
- Genetic Determinants of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureusPublication . Pardos de la Gandara, Maria; Borges, Vitor; Chung, Marilyn; Milheiriço, Catarina; Gomes, João Paulo; de Lencastre, Herminia; Tomasz, AlexanderMethicillin-resistant Staphylococcus aureus (MRSA) strains carry either a mecA- or a mecC-mediated mechanism of resistance to beta-lactam antibiotics, and the phenotypic expression of resistance shows extensive strain-to-strain variation. In recent communications, we identified the genetic determinants associated with the stringent stress response that play a major role in the antibiotic resistant phenotype of the historically earliest "archaic" clone of MRSA and in the mecC-carrying MRSA strain LGA251. Here, we sought to test whether or not the same genetic determinants also contribute to the resistant phenotype of highly and homogeneously resistant (H*R) derivatives of a major contemporary MRSA clone, USA300. We found that the resistance phenotype was linked to six genes (fruB, gmk, hpt, purB, prsA, and relA), which were most frequently targeted among the analyzed 20 H*R strains (one mutation per clone in 19 of the 20 H*R strains). Besides the strong parallels with our previous findings (five of the six genes matched), all but one of the repeatedly targeted genes were found to be linked to guanine metabolism, pointing to the key role that this pathway plays in defining the level of antibiotic resistance independent of the clonal type of MRSA.
- Impact of Loci Nature on Estimating Recombination and Mutation Rates in Chlamydia trachomatisPublication . Ferreira, Rita; Borges, Vitor; Nunes, Alexandra; Nogueira, Paulo Jorge; Borrego, Maria José; Gomes, João PauloThe knowledge of the frequency and relative weight of mutation and recombination events in evolution is essential for understanding how microorganisms reach fitted phenotypes. Traditionally, these evolutionary parameters have been inferred by using data from multilocus sequence typing (MLST), which is known to have yielded conflicting results. In the near future, these estimations will certainly be performed by computational analyses of full-genome sequences. However, it is not known whether this approach will yield accurate results as bacterial genomes exhibit heterogeneous representation of loci categories, and it is not clear how loci nature impacts such estimations. Therefore, we assessed how mutation and recombination inferences are shaped by loci with different genetic features, using the bacterium Chlamydia trachomatis as the study model. We found that loci assigning a high number of alleles and positively selected genes yielded nonconvergent estimates and incongruent phylogenies and thus are more prone to confound algorithms. Unexpectedly, for the model under evaluation, housekeeping genes and noncoding regions shaped estimations in a similar manner, which points to a nonrandom role of the latter in C. trachomatis evolution. Although the present results relate to a specific bacterium, we speculate that microbe-specific genomic architectures (such as coding capacity, polymorphism dispersion, and fraction of positively selected loci) may differentially buffer the effect of the confounding factors when estimating recombination and mutation rates and, thus, influence the accuracy of using full-genome sequences for such purpose. This putative bias associated with in silico inferences should be taken into account when discussing the results obtained by the analyses of full-genome sequences, in which the "one size fits all" approach may not be applicable.
- INSaFLU: a bioinformatics framework that potentiates the integration of influenza genome sequencing data for an enhanced and harmonized global flu surveillancePublication . Borges, VitorProcurarei dar um perspetiva geral da importância da análise total do genoma viral na vigilância laboratorial (e actividades de I&D) do vírus influenza, destacando o potencial papel da plataforma INSaFLU nesta revolução tecnológica / científica. Abordarei ainda alguns desafios (e perspetivas futuras) associados à integração da informação gerada com a sequenciação total do genoma de agentes patogénicos na descodificação da interação destes agentes com o seu hospedeiro humano.
- A large outbreak of Legionnaires’ Disease in an industrial town in PortugalPublication . George, Francisco; Shivaji, Tara; Pinto, Catia Sousa; Serra, Luis Antonio Oliveira; Valente, João; Albuquerque, Maria João; Vicêncio, Paula Cristina Olivença; San-Bento, Ana; Diegues, Paulo; Nogueira, Paulo Jorge; Marques, Teresa; Rebelo, Helena; Costa, Filipa; Rodrigues, Raquel; Nunes, Alexandra; Borges, Vitor; Gomes, João Paulo; Sampaio, Daniel; Barreiro, Paula; Duarte, Silvia; Carpinteiro, Dina; Mendonça, Joana; Silva, Catarina; Vieira, Luís; Simões, Maria Joao; Gonçalves, Paulo; Nunes, Baltazar; Dias, Carlos; Machado, Jorge; Almeida, Fernando; Goncalves, Elsa A; Carvalho, Lucilia; Viterbo, Pedro; Jardim, Dilia; Lacasta, Nuno; Boavida, Filomena; Perez, Ana; Santana, Isabel; Matias, Paula; Banza, Nuno; Rabacal, CarlosBackground: We describe the investigation and control of an outbreak of Legionnaires’ disease in Portugal in October, November and December 2014. Methods: Confirmed cases were individuals with pneumonia, laboratory evidence of Legionella pneumophila serogroup 1 and exposure, by residence, occupational or leisure to the affected municipalities. 49 possible sources were reduced to four potential sources, all industries with wet cooling system, following risk assessment. We geo-referenced cases’ residences and the location of cooling towers defining four study areas 10km buffer centered on each cooling tower system. We compared the number of cases with expected numbers, calculated from the outbreak's attack rates applied to 2011 census population. Using Stones’ Test, we tested observed to expected ratios for decline in risk, with distance up to 10km four directions. Isolates of Legionella pneumophila were compared using molecular methods. Results: We identified 403 cases, 377 of which were confirmed, 14 patients died. Patients became ill between 14 October and 2 December. A NE wind and thermal inversion were recorded during the estimated period of exposure. Disease risk was highest in people living south west from all of the industries identified and decreased with distance (p<0.001). 71 clinical isolates demonstrated an identical SBT profile to an isolate from a cooling tower. Whole genome sequencing identified an unusual L. pneumophila subsp. fraseri serogroup 1 as the outbreak causative strain, and confirmed isolates’ relatedness. Conclusions: Industrial wet cooling systems, bacteria with enhanced survival characteristics and a combination of climatic conditions contributed to the second largest outbreak of Legionnaires’ disease recorded internationally.
- Multilocus sequencing typing as a tool to investigate childhood Haemophilus influenzae invasive disease in PortugalPublication . Bettencourt, Célia; Borges, Vitor; Gonçalo-Marques, José; Cunha, Florbela; Bajanca-Lavado, Maria Paula; on behalf of Portuguese Study Group of Invasive Haemophilus influenzae Disease of the Pediatric Infectious Disease SocietyBackground: Haemophilus influenzae is an important cause of serious childhood invasive disease despite the use of the vaccine against serotype b strains (Hib). Six capsular types, a-f, have been identified to date, although most of strains are non-capsulated (NC). Multilocus Sequencing Typing (MLST) is a powerful method that allows a precise and unambiguous characterization of H. influenzae genotypes. A partnership between the National Institute of Health and the Society for Paediatric Infectious Diseases aimed to characterize invasive childhood infection in Portugal. The objective of this study was to genotype isolates by MLST to follow the epidemiology of disease. Material / Methods: This study was conducted between 1 January 2010 and 31 December 2015. During this period 41 H. influenzae strains were analysed, mostly isolated from blood (88%). Antibiotic resistance was assessed by the microdilution assay and β-lactamase production was determined with nitrocefin. Capsular status was characterized by polymerase chain reaction using primers and conditions described in the literature. MLST was performed by amplifying and sequencing internal fragments of the 7 housekeeping genes (adk, atpG, frdB, fucK, mdh, pgi and recA). Sequences were analyzed and submitted to the MLST website http://pubmlst.org/hinfluenzae/ for assignment of the sequence type (ST). To display the allelic distances between the obtained STs, we applied the goeBURST algorithm implemented in the PHYLOViZ platform. Results: Antimicrobial susceptibility testing showed that most strains were susceptible to all beta-lactams studied, with only three strains being ampicillin resistant due to beta-lactamase production. Most of invasive disease was due to the presence of NC strains (27/41; 66%), while 14 isolates (34%) were capsulated and characterized as follow: two serotype a (5%), 10 b (24%) and two f (5%). As expected, MLST typing revealed high genetic variability among 27 NC isolates, which had 24 (89%) different sequence types (STs), with four new STs represented by previously unidentified allele combinations. In opposition, capsulated isolates were very clonal: all 10 Hib were assigned to CC6 (eight strains ST6, one ST 1149, one ST 190), the two Hia strains were assigned to CC 23 (ST 23) and the two Hif belonged to CC124 (ST 124 and ST 1188) (Figure 1). Conclusions: Our data indicate that invasive disease among Portuguese children is now due to highly genetically diverse, fully susceptible NC strains, suggesting that no particular virulent clone is responsible for epidemiological change of disease, after vaccine implementation in the year 2000. Nevertheless, we are concerned about Hib disease (24% of the isolates) despite the higher vaccine coverage. MLST typing continues to show a high genetic diversity among NC strains and clonal relationships among capsulated isolates. In conclusion, in order to monitor the evolving dynamics of this pathogen and the epidemiology of invasive disease, ongoing surveillance is needed to monitor the true magnitude of this problem.
- Phenotypic signatures and genetic determinants of oxacillin tolerance in a laboratory mutant of Staphylococcus aureusPublication . Chung, Marilyn; Borges, Vitor; Gomes, João Paulo; de Lencastre, Herminia; Tomasz, AlexanderAddition of β-lactam antibiotics to growing cultures of bacteria inhibit synthesis of the bacterial cell wall peptidoglycan accompanied by killing (loss of viable titer) and lysis (physical disintegration) of the cells. However, it has also been well established that these antibiotics are not effective in killing non-growing or slow-growing bacteria and the mechanism of this "antibiotic tolerance" is not well understood. In this study, we report on the genetic basis and phenotypic properties of an antibiotic tolerant derivative of the methicillin susceptible S. aureus strain 27s. Cultures were exposed to "pulses" of high concentrations of oxacillin followed by outgrowth of the surviving bacteria. This procedure quickly selected for antibiotic tolerant mutants with an increased ability to survive antibiotic treatment without increase in the MIC value for the antibiotic. Such mutants also exhibited longer lag phase, decreased lysis, virtually no change in antibiotic susceptibilities, cross tolerance to D-cycloserine and vancomycin, and increase in biofilm formation in the presence of high concentrations of oxacillin. Whole genome sequencing showed that these altered properties were linked to mutations in the atl and gdpP genes.