Mário Ramirez Lab

Molecular Microbiology & Infection

Despite the successful use of antibiotics and vaccination, bacterial infections are still a major cause of morbidity and mortality worldwide. The changing demographics are shifting the attention to older adults where selective pressures may be radically different from those found in children. Several studies showed that bacterial populations are dominated by a few clones. The plasticity of bacterial genomes means that different isolates can carry a distinct array of antibiotic resistance and virulence genes. However, the relationship between carrying a certain gene complement and becoming a successful clone remains elusive.

We have documented the bacterial population structure of several pathogens of the genus //Streptococcus// and found differences between bacteria that are asymptomatically carried and those causing distinct infections in the various age groups. In addition, we identified genes that are unevenly distributed in the bacterial population, potentially explaining the propensity of certain clones for particular hosts or infections. We have also studied the flow of genetic information between bacteria and the factors enhancing or limiting these exchanges and the role of mobile genetic elements in bacterial diversity. We are currently exploring the differences between bacterial populations at the whole-genome level.

We are refining existing approaches to handle high throughput sequence (HTS) data and are developing tools for storing and mining this data in a unified platform, integrating information from existing databases. This is reflected in the development of novel bioinformatic tools with a focus on HTS. We hope to get a detailed view of the genetic differences between bacterial clones and to identify candidate genes to explain their different abundance. We are also looking at streptococci causing infections in humans and animals to identify key events allowing the adaptation to different host species and to evaluate the current potential for zoonotic acquisition. Understanding the dynamics and responses of a bacterial population to the multiple selective pressures imposed on it and the key genetic events allowing the differentiation of specific clones will allow us to better predict bacterial pathogen evolution.

Our research also produces important epidemiological information allowing us to anticipate the potential benefits of vaccination or guiding the optimal empirical therapy for infections of suspected streptococcal etiology.

Research Team

Research Areas

• Population biology and genomics
• Bioinformatics
• Detection of antimalarial drug resistance
• Molecular epidemiology
• Diagnostic tools
• Antibiotic resistance
• Vaccines

Ongoing Research Projects

2020/2022 Recursos de Computação Avançada para Investigação e Inovação. Coordinator: Mário Ramirez. Funding Agency: Fundação para a Ciência e a Tecnologia.

2018/2021 Ferramentas para análise filogenética em larga escala. Coordinator: João Carriço. Funding Agency: Fundação para a Ciência e a Tecnologia.

Selected Publications

van der Linden M, Mamede R, Levina N, Helwig P, Vila-Cerqueira P, Carriço JA, Melo-Cristino J, Ramirez M, Martins ER (2020). Heterogeneity of penicillin-non-susceptible group B streptococci isolated from a single patient in Germany. Journal of Antimicrobial Chemotherapy 75(2):296–299.

Pinho MD, Foster G, Pomba C, Machado MP, Baily JL, Kuiken T, Melo-Cristino J, Ramirez M, Portuguese Group for the Study of Streptococcal Infections. 2019. Streptococcus canis are a single population infecting multiple animal hosts despite the diversity of the universally present M-like protein SCM. Front Microbiol 10:631.

Silva-Costa C, Brito MJ, Aguiar SI, Lopes JP, Ramirez M, Melo-Cristino J, Portuguese Group for the Study of Streptococcal Infections, Portuguese Study Group of Invasive Pneumococcal Disease of the Pediatric Infectious Disease Society. 2019. Dominance of vaccine serotypes in pediatric invasive pneumococcal infections in Portugal (2012-2015). Sci Rep 9:6.

Echániz-Aviles G, Guerreiro SI, Silva-Costa C, Mendes CI, Carriço JA, Carnalla-Barajas MN, Soto-Noguerón A, Velazquez-Meza ME, Melo-Cristino J, Luévanos-Velazquez A, Martínez-Medina L, Vázquez-Larios MDR, Ramirez M. 2019. Streptococcus pneumoniae serotype 3 in Mexico (1994-2017): decrease of the unusual CC4909 lineage post-PCV13 introduction. J Clin Microbiol. 57 e01354-18.

Jesus TF, Ribeiro-Gonçalves B, Silva DN, Bortolaia V, Ramirez M, Carriço JA. 2019. Plasmid ATLAS: plasmid visual analytics and identification in high-throughput sequencing data. Nucleic Acids Res 47:D188–D19.

Pato C, Melo-Cristino J, Ramirez M, Friães A, Portuguese Group for the Study of Streptococcal Infections. 2018. Streptococcus pyogenes causing skin and soft tissue infections are enriched in the recently emerged emm89 clade 3 and are not associated with abrogation of CovRS. Front Microbiol 9:2372.

Branco A, Francisco D, Hänscheid T. 2018. Is there a “normal” oxygen concentration for in vitro Plasmodium cultures? Trends Parasitol 34:811–812.

Silva-Costa C, Brito MJ, Pinho MD, Friães A, Aguiar SI, Ramirez M, Melo-Cristino J, Portuguese Group for the Study of Streptococcal Infections, Portuguese Study Group of Invasive Pneumococcal Disease of the Pediatric Infectious Disease Society. 2018. Pediatric complicated pneumonia caused by Streptococcus pneumoniae serotype 3 in 13-valent pneumococcal conjugate vaccinees, Portugal, 2010-2015. Emerging Infect Dis 24: 1307–1314.

Silva M, Machado MP, Silva DN, Rossi M, Moran-Gilad J, Santos S, Ramirez M, Carriço JA. 2018. chewBBACA: A complete suite for gene-by-gene schema creation and strain identification. Microb Genom. 4. doi: 10.1099/mgen.0.000166.

Lopes E, Fernandes T, Machado MP, Carriço JA, Melo-Cristino J, Ramirez M, Martins ER, The Portuguese Group For The Study Of Streptococcal Infections. Increasing macrolide resistance among Streptococcus agalactiae causing invasive disease in non-pregnant adults was driven by a single capsular-transformed lineage, Portugal, 2009 to 2015. Euro Surveill. 2018;23.

Carriço JA, Rossi M, Moran-Gilad J, Van Domselaar G, Ramirez M. 2018. A Primer on Microbial Bioinformatics for non-bioinformaticians. Clin Microbiol Infect. 24:342–349.

Hänscheid T, Grobusch MP. 2017. Modern hematology analyzers are very useful for diagnosis of malaria and, crucially, may help avoid misdiagnosis. J Clin Microbiol 55:3303–3304.

Martins ER, Pedroso-Roussado C, Melo-Cristino J, Ramirez M, Portuguese Group for the Study of Streptococcal Infections. 2017. Streptococcus agalactiae causing neonatal infections in Portugal (2005-2015): diversification and emergence of a CC17/PI-2b multidrug resistant sublineage. Front Microbiol 8:499.

Useful Links