ITQB: MG - PhD Theses
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- Unfolding the physiological roles of the binding of Atl to eDNA in Staphylococcus aureusPublication . Grilo, Maria Inês Ramos; Lencastre, Hermínia; Ludovice, Ana Madalena; Sobral, RitaStaphylococcus aureus is usually a commensal organism of the human’s microbiota, although it can become invasive when the host’s defenses are breached, becoming an important nosocomial opportunistic pathogen, with high morbidity and mortality rates across the globe. It is responsible for a wide array of infections that range from minor skin and soft tissue infections to more severe ones, such as endocarditis, osteomyelitis and sepsis. This microorganism harbors a plethora of virulence factors that alongside its capacity to acquire resistance to virtually all antibiotics have enabled it to become one of the most prominent pathogens of this era. In fact, S. aureus is one of the major causes for infections associated with indwelling devices, which are usually related with biofilm development. Biofilms are multicellular sessile microbial communities in which cells are attached to a surface and/or to other cells and encased within a self-produced protective extracellular matrix. The biofilm forming capacity of S. aureus is part of the myriad of virulence mechanisms that enables this bacterium to resist both antibiotic treatment and the action of the host immune system.
- The role of co-colonization in pneumococcal ecology and evolutionPublication . Valente, Carina; Lencastre, Hermínia; Sá-Leão, RaquelStreptococcus pneumoniae (or pneumococcus) is a frequent colonizer of the nasopharynx and an important cause of infectious diseases, with a high rate of morbidity and mortality worldwide, particularly among young children, the elderly and the immunocompromised. Despite this high burden of morbidity and mortality, invasive pneumococcal disease is incidental. Nasopharyngeal colonization is the preferred lifestyle for the pneumococcus, its prevalence being particularly high among young children.(...)
- Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Portugal:Publication . Tavares, Ana Lopes; Lencastre, Hermínia; Ryder, Maria MiragaiaMethicillin-resistant Staphylococcus aureus (MRSA), a human pathogen confined to hospitals (HAMRSA) for over 30 years have been emerging worldwide in the last two decades as a leading cause of severe infections in healthy individuals in the community (CA-MRSA). Despite its clinical significance, in the beginning of our studies no information existed on the prevalence, and population structure of CA-MRSA in Portugal. Moreover, it remained to be clarified how CA-MRSA emerged in our country. In particular, it was not known if CA-MRSA emerged locally by acquisition of the staphylococcal cassette chromosome mec (SCCmec) by established methicillin-susceptible S. aureus (MSSA) in the community, if they were imported from abroad or have escaped from the hospital.(...)
- Amidation of peptidoglycan in Staphylococcus aureusPublication . Figueiredo, Teresa Carla de Almeida; Lencastre, Hermínia deStaphylococcus aureus is one of the most important contemporary human pathogens. The evolutionary “success” of this species is closely related to its remarkably capacity to acquire antibiotic resistance traits. In this perspective, it is important to extend our knowledge concerning the mechanisms of antibiotic resistance in S. aureus and to identify new antimicrobials targets.(...)
- Insights into the epidemiology of drug-resistant Streptococcus pneumoniae and closely-related streptococci in the era of conjugate vaccinesPublication . Simões, Alexandra Sofia Oliveira; Sá-Leão, Raquel; Lencastre, Hermínia deIn Portugal, the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) has led to significant changes in the population structure of Streptococcus pneumoniae. However, the levels of antimicrobial resistance have not decreased and have been a matter of concern. (...)
- Epidemiological studies of Streptococcus pneumoniae carriage in the post-vaccination era among two risk groups: children and the elderlyPublication . Nunes, Sónia; de Lencastre, Hermínia; Sã-Leão, RaquelStreptococcus pneumoniae is a global cause of disease including pneumonia, otitis media, conjunctivitis, sepsis, and bacterial meningitis. These infections are not essential to the transmission or long-term survival of the bacterium; indeed, S. pneumoniae depends on asymptomatic colonization of the human nasopharynx for its dissemination to additional hosts. Considering this, colonization studies are a good way to monitor changes in the pneumococcal epidemiology that may result from the use of antibiotics and vaccines. The molecular characterization of pneumococci is crucial to assess these changes which highlight the need for the development and validation of easier and faster methods of molecular typing. Since 1996 our group has been monitoring the pneumococcal population colonizing children attending day care centers. However, for several years these studies have been confined to the Lisbon area. In this PhD we have addressed this situation by including other regions of Portugal in our study. In addition, we have started to study pneumococcal colonization in the elderly, the other age group where the incidence of pneumococcal infections is high. This thesis summarizes five studies conducted during this PhD. The first four studies were focused on the pneumococcal epidemiology among the two age groups where the rates of pneumococcal disease are highest: children up to six years old and adults older than 60 years. The fifth and last study describes the evaluation and validation of a new genotyping strategy for pneumococci.(...)
- Staphylococcus aureus: towards a comprehensive view on epidemiology and clonal spreadPublication . Conceição, Teresa; de Lencastre, Hermínia; Aires de Sousa, Marta; Westh, HenrikStaphylococcus aureus is known for its extraordinary capacity of colonizing asymptomatically the anterior nares of humans. A high versatility allied to the successive accumulation of resistance to almost all clinically available antibiotics, made S. aureus a major human pathogen worldwide. Soon after the introduction of methicillin into clinical practice, methicillin resistant S. aureus (MRSA) emerged as a major pathogen in hospitals worldwide, and more recently in the community as well. Methicillin susceptible S. aureus (MSSA) are also an important problem. MSSA is responsible from mild to severe invasive infections, commonly due to enhanced virulence content, rather than accumulation of resistance determinates. However, many gaps in the knowledge of the epidemiology of MSSA remain to be clarified.(...)
- Massive shift in the pneumococcal nasopharyngeal flora after the 7-valent conjugate vaccine: epidemiological studies and testing pathogenic potential in animal modelsPublication . Frazão, Nelson; de Lencastre, Hermínia; Tomasz, AlexanderAlthough it exists mostly as a commensal bacterium colonizing the human nasopharynx, particularly in children, the Gram-positive bacterium Streptococcus pneumoniae, is also a major human pathogen that can cause a wide range of diseases, which include otitis media, sinusitis, pneumonia, and such life-threatening afflictions as bloodstream infection and meningitis. Created to protect children against pneumococcal disease, the 7-valent pneumococcal conjugate vaccine (PCV7) showed high efficacy in preventing disease caused by the serotypes included in the vaccine, the so-called vaccine types (VTs). Since colonization is an essential first step to develop pneumococcal disease, it is of importance to investigate the effect of this vaccine on the degree of colonization, on changes in the composition of the nasopharyngeal flora and the virulence potential of the non vaccine type (NVT) strains.(...)