Browsing by Author "Gomes, Pedro"
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- Insights on the Mycobacterium tuberculosis population structure associated with migrants from Portuguese-speaking countries over a three-year period in greater Lisbon, Portugal: Implications at the public health levelPublication . Pereira, Catarina; Gomes, Pedro; Taveira, Ricardo; Silva, Carla; Maltez, Fernando; Macedo, Rita; Costa, Catarina; Couvin, David; Rastogi, Nalin; Viveiros, Miguel; Perdigão, João; Portugal, IsabelTuberculosis among foreign-born patients is a key indicator of country-level epidemiological profiles and, of an increasing concern in Europe given the more intensified migratory waves of refugees. Since Portugal presents a lower immigrant-associated TB incidence rate when compared to other European countries, we sought to characterize the epidemiology and transmission dynamics among the foreign-born population coming from Portuguese-speaking countries that are associated with higher TB incidences. In the present study we analyzed 133 Mycobacterium tuberculosis isolates obtained from foreign-born individuals over a three-year period in Lisbon, Portugal, using molecular epidemiological methods such as spoligotyping and 24-loci MIRU-VNTR. Moreover, all strains were subjected to drug susceptibility testing. The genetic profiles obtained suggest that strain importation from Portuguese speaking countries plays a less important role in TB epidemiology but instead argue in favor of a high degree of penetrance of Portuguese endemic strains to the migrant population, including multidrug resistant strains, which is particularly relevant to active screening programs.
- Levofloxacin-loaded bone cement delivery system: highly effective against intracellular bacteria and Staphylococcus aureus biofilmsPublication . Ferreira, Magda; Rzhepishevska, Olena; Grenho, Liliana; Malheiros, Danila; Gonçalves, Lídia; Almeida, António J.; Jordao, Luisa; Ribeiro, Isabel A.; Ramstedt, Madeleine; Gomes, Pedro; Bettencourt, AnaStaphylococcus aureus is a major pathogen in bone associated infections due to its ability to adhere and form biofilms on bone and/or implants. Moreover, recrudescent and chronic infections have been associated with S. aureus capacity to invade and persist within osteoblast cells. With the growing need of novel therapeutic tools, this research aimed to evaluate some important key biological properties of a novel carrier system composed of acrylic bone cement (polymethylmethacrylate - PMMA), loaded with a release modulator (lactose) and an antibiotic (levofloxacin). Levofloxacin-loaded bone cement (BC) exhibited antimicrobial effects against planktonic and biofilm forms of S. aureus (evaluated by a flow chamber system). Moreover, novel BC formulation showed high anti-bacterial intraosteoblast activity. This fact led to the conclusion that levofloxacin released from BC matrices could penetrate the cell membrane of osteoblasts and be active against S. aureus strains in the intracellular environment. Furthermore, levofloxacin-BC formulations showed no significant in vitro cytotoxicity and no allergic potential (measured by the in vivo chorioallantoic membrane assay). Our results indicate that levofloxacin-loaded BC has potential as a local antibiotic delivery system for treating S. aureus associated bone infections.
- Using genomics to understand the origin and dispersion of multidrug and extensively drug resistant tuberculosis in PortugalPublication . Perdigão, João; Gomes, Pedro; Miranda, Anabela; Maltez, Fernando; Machado, Diana; Silva, Carla; Phelan, Jody E.; Brum, Laura; Campino, Susana; Couto, Isabel; Viveiros, Miguel; Clark, Taane G.; Portugal, IsabelPortugal is a low incidence country for tuberculosis (TB) disease. Now figuring among TB low incidence countries, it has since the 1990s reported multidrug resistant and extensively drug resistant (XDR) TB cases, driven predominantly by two strain-types: Lisboa3 and Q1. This study describes the largest characterization of the evolutionary trajectory of M/XDR-TB strains in Portugal, spanning a time-period of two decades. By combining whole-genome sequencing and phenotypic susceptibility data for 207 isolates, we report the geospatial patterns of drug resistant TB, particularly the dispersion of Lisboa3 and Q1 clades, which underly 64.2% and 94.0% of all MDR-TB and XDR-TB isolates, respectively. Genomic-based similarity and a phylogenetic analysis revealed multiple clusters (n = 16) reflecting ongoing and uncontrolled recent transmission of M/XDR-TB, predominantly associated with the Lisboa3 and Q1 clades. These clades are now thought to be evolving in a polycentric mode across multiple geographical districts. The inferred evolutionary history is compatible with MDR- and XDR-TB originating in Portugal in the 70's and 80's, respectively, but with subsequent multiple emergence events of MDR and XDR-TB particularly involving the Lisboa3 clade. A SNP barcode was defined for Lisboa3 and Q1 and comparison with a phylogeny of global strain-types (n = 28 385) revealed the presence of Lisboa3 and Q1 strains in Europe, South America and Africa. In summary, Portugal displays an unusual and unique epidemiological setting shaped by >40 years of uncontrolled circulation of two main phylogenetic clades, leading to a sympatric evolutionary trajectory towards XDR-TB with the potential for global reach.