Hermínia de Lencastre Lab

	The long-range interest of the laboratory has been in the epidemiology, genetics, evolutionary and biochemical mechanisms of antibiotic resistant pathogens, specifically, staphylococci, enterococci and Streptococcus pneumoniae.
	Hermínia de Lencastre Professora Catedrática PhD in Biology 1981 UNL Phone (+351) 214469538 | Extension 1537/ 1538 Email hml@itqb.unl.pt

Research Interests

The emergence and spread of antibiotic resistant clones of Staphylococcus spp., enterococci and Streptococcus pneumoniae pose a public health threat worldwide. The phenomenon also presents fascinating problems of basic science, such as the evolutionary origin of resistance genes; the mechanism of antibiotic resistance and the question of what combination of determinants provides the epidemic “success” of these pathogens. Our laboratory has been over the period of many years actively involved both in the public health related and also in the biological aspects of this problem.

Methicillin-resistant Staphylococcus aureus (MRSA) are a major cause of infections worldwide not only in hospitals but also in the healthy community, posing a very high public health concern. We aim to characterize the molecular epidemiology of MRSA in hospitals, in the community and livestock associated in a One Health perspective, as well as to track the evolutionary origin and spread of the ß-lactam resistance genes. In recent years, hospital infections due to methicillin susceptible S. aureus have been increasing, which sparked our interest also in the understanding the molecular evolution of MSSA. Other staphylococcal species are also under study as they are thought to be important reservoirs and key players in the evolution of ß-lactam resistance determinants. Since 2015 our work on Coagulase negative staphylococci has been carried out in collaboration with  Dr. Maria Miragaia Laboratory.

Moreover, we investigate not only the most common molecular mechanism leading to ß -lactam resistance in MRSA that involve the acquisition of a foreign genetic cassette carrying the genetic determinant for ß-lactam resistance, but also alternative mechanisms developed by S. aureus in order to avoid or resist the killing action of ß-lactam antibiotics. The biosynthetic steps of peptidoglycan, a major cell wall component and target of these antibiotics, have been also one of the focus of our studies. We use several approaches, including conventional molecular genetics’ techniques as well as next-generation sequencing technologies.

Enterococci are opportunistic pathogens that colonize the gastrointestinal tract of humans and animals and have an extraordinary capacity of acquiring antimicrobial resistance namely to vancomycin, one of the last resource antibiotics. Vancomycin resistant Enterococcus faecium (VRE) have been increasingly reported in hospitals usually associated to major resistant lineages and to vancomycin resistance determinants, vanA or vanB. Our goal is to apply a One Health approach, studying samples from humans, animals and the environment, to understand the VRE population structure, identify prevalence of vancomycin resistance determinants and unveiling the major reservoirs outside hospitals.

S. pneumoniae remains a leading cause of morbidity and mortality worldwide causing a wide range of infectious diseases. Its sole ecological niche is the human nasopharynx and children of preschool age their major reservoir. Our laboratory has been engaged since 1996 in extensive studies aimed to better understand the nasopharyngeal ecosystem and how it is affected by interventions such as antibiotic use and vaccines. Since 2011 our work on Pneumo has been carried out in collaboration with Dr. Raquel Sá-Leão Laboratory.

Our research is done in collaboration with Portuguese and foreign scientists worldwide through different initiatives and has been supported by the European Community, Fundação Para a Ciência e Tecnologia and Fundação Calouste Gulbenkian.

Group Members

•  

  Alexander Tomasz, Ph.D., Adjunct Full Professor

• Catarina Milheiriço, Ph.D., Post-Doc

• Teresa Conceição, Ph.D., Post-Doc

• Ana Amaral, Ms Student

• Marta Aires de Sousa, PhD, Escola Superior de Saúde da Cruz Vermelha Portuguesa

• Manuela Nogueira, Administrative Assistant

Selected Publications

1. Lee, A., H. de Lencastre, J. Garau, J. A. Kluytmans, S. Malhotra-Kumar, A. Peschel, and S. Harbarth. 2018. Methicillin-resistant Staphylococcus aureus. Nat Rev Dis Primers. 4: 18033. doi: 10.1038/nrdp.2018.33.

2. Conceição, T., H. Martins, S. Rodrigues, H. de Lencastre, and M. Aires-de-Sousa. 2019. Staphylococcus aureus nasal carriage among homeless population in Lisbon, Portugal. Eur J Clin Microbiol Infect Dis. 2019 Nov;38(11):2037-2044. doi: 10.1007/s10096-019-03638-4. Epub 2019 Jul 22.

3. Milheiriço, C., A. Tomasz and H. de Lencastre. 2022. Impact of the stringent stress response on the expression of methicillin resistance in staphylococcaceae strains carrying mecA, mecA1 and mecC. Antibiotics. 11(2):255; doi: 10.3390/antibiotics11020255.

4. Immergluck, L. C., X. Lin, R. Geng, M. Edelson, F. Ali, C. Li, T. J. Lin, C. Khalida, N. Piper-Jenks, M. Pardos de la Gandara, H. de Lencastre, A. Tomasz, T. H. Evering, R. G Kost, R. Vaughan, and J. N. Tobin. 2023..Molecular epidemiologic and geo-spatial characterization of Staphylococcus aureus cultured from skin and soft tissue infections from United States-born and Immigrant patients living in New York City. Antibiotics 2023, 12(10):1541. doi: 10.3390/antibiotics12101541.

5. Conceição T., M. Felgueiras, V. Alves, and H. de Lencastre. 2023. Unveiling the first Staphylococcus argenteus infection in Portugal. Acta Med Port. 36(7-8):531-533. doi: 10.20344/amp.19892.

Laboratory's Website

For further information visit the laboratory's website (in revision)

Genética Molecular (PT)

Um dos principais objetivos do nosso laboratório é o estudo do mecanismo de resistência aos antibióticos ß-lactâmicos em Staphylococcus aureus, cujo elemento central é o gene exógeno mecA. Pretendemos responder a duas questões importantes em biologia evolutiva, nomeadamente o(s) mecanismos(s) de aquisição do gene mecA pela bactéria hospedeira e como é que este gene proporciona um fenótipo de elevada resistência. Para além disso, pretendemos perceber a natureza de mecanismos de resistência alternativos desenvolvidos por S. aureus por forma a evitar ou resistir à ação letal dos antibióticos ß-lactâmicos.

Outro objetivo é caracterizar, por métodos de epidemiologia molecular e por sequenciação completa do genoma, a estrutura populacional de bactérias patogénicas - Staphylococcus aureus, estafilococos coagulase negativos e enterococcus, responsáveis por um elevado número de infeções em hospitais e na comunidade em todo o mundo, constituindo uma causa importante de morbilidade e mortalidade. Pretendemos ainda, pela caracterização molecular de estirpes provenientes destes dois ambientes, estabelecer ligações epidemiológicas entre eles, compreender os mecanismos moleculares da sua evolução e identificar os principais reservatórios de estirpes multiresistentes.

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