MolMicro of Bacterial Pathogens
The bacterial cell wall is a complex structure which suffers constant synthesis and degradation to allow for growth and division. Besides its structural role, it also provides a communication platform with the environment.
In our lab, we study the cell wall of the human pathogen Staphylococcus aureus, leading cause of hospital-acquired infections, mainly due to its capacity to resist antibiotics. We combine biochemical and genetic approaches to understand the molecular mechanisms which associate the cell wall to the physiology and mechanisms of resistance of this pathogen. We have a specific interest in the study of biofilm formation, host interactions and application of biophysical methods.
Finding new strategies to fight bacterial pathogens
The number of antibiotics that remain efficient against bacterial pathogens, namely multidrug resistant strains, is alarmingly decreasing and new strategies are urgently needed to deal with this global crisis. Understanding the mode of action of new and old drugs is an essential step. A new plant-derivative compound, with high antimicrobial activity and low cytotoxicity, was found to target the bacterial cell wall and membrane permeability, without causing cell disruption.
In another study, sub-inhibitory concentrations of oxacillin, a well-known antibiotic of the beta-lactam class, were shown to exacerbate the viscosity behavior of a Staphylococcus aureus culture exposed to shear stress.
- “StaphOUT- Fighting Staphylococcus aureus - Peptidoglycan amidation as a new target”. FCT-MCTES. Total and Unit funding: €239,900. Rita Sobral (PI)
- “Microfluidics Liquid Crystal Based Bifunctional Bacterial Infection Sensor”, FCT-MCTES, Funding: €159,912, Rita Sobral (Co-PI)
- “Amidation of the peptidoglycan of Gram-positive bacteria: an unexplored potential target for antibiotics”, FCT-MCTES, Total funding: €165,000, Unit funding: €60,872, Rita Sobral (Collaborator)
- “A new target inside an old molecule: glutamate amidation of peptidoglycan”, ESCMID, Funding: €20,000, Rita Sobral (PI)
Portela, R; Faria, NA; Mwangi, M; Miragaia, M; de Lencastre, H; Tomasz, A; Sobral, RG. 2022. Analysis of a Cell Wall Mutant Highlights Rho-Dependent Genome Amplification Events in Staphylococcus aureus. MICROBIOLOGY SPECTRUM, DOI: 10.1128/spectrum.02483-21
Bárbara VGonçalves; Raquel Portela; Ricardo Lobo; Teresa AFigueiredo; Inês RGrilo; Ana Madalena Ludovice; Hermínia de Lencastre; Jorge SDias; Rita GSobral. 2019. Role of MurT C-Terminal Domain in the Amidation of Staphylococcus aureus Peptidoglycan. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, DOI: 10.1128/aac.00957-19
Raquel Portela; Catarina RLeal; Pedro LAlmeida; Rita GSobral. 2019. Bacterial cellulose: a versatile biopolymer for wound dressing applications. Microbial Biotechnology, 12(4), DOI: 10.1111/1751-7915.13392
Harrison, Ewan M.; Ba, Xiaoliang; Coll, Francesc; Blane, Beth; Restif, Olivier; Carvell, Henry; Köser, Claudio U.; Jamrozy, Dorota; Reuter, Sandra; Lovering, Andrew; Gleadall, Nicholas; Bellis, Katherine L.; Uhlemann, Anne Catrin; Lowy, Franklin D.; Massey, Ruth C.; Grilo, Inês R.; Sobral, Rita; Larsen, Jesper; Rhod Larsen, Anders; Vingsbo Lundberg, Carina; Parkhill, Julian; Paterson, Gavin K.; Holden, Matthew T.G.; Peacock, Sharon J.; Holmes, Mark A.. 2019. Genomic identification of cryptic susceptibility to penicillins and β-lactamase inhibitors in methicillin-resistant Staphylococcus aureus. Nature Microbiology, DOI: 10.1038/s41564-019-0471-0
Espadinha, D; Sobral, RG; Mendes, CI; Meric, G; Sheppard, SK; Carrico, JA; de Lencastre, H; Miragaia, M. 2019. Distinct Phenotypic and Genomic Signatures Underlie Contrasting Pathogenic Potential of Staphylococcus epidermidis Clonal Lineages. Frontiers in Microbiology, 10, DOI: 10.3389/fmicb.2019.01971
Reichmann, Nathalie T.; Tavares, Andreia C.; Saraiva, Bruno M.; Jousselin, Ambre; Reed, Patricia; Pereira, Ana R.; Monteiro, João M.; Sobral, Rita G.; VanNieuwenhze, Michael S.; Fernandes, Fábio; Pinho, Mariana G.. 2019. SEDS–bPBP pairs direct lateral and septal peptidoglycan synthesis in Staphylococcus aureus. Nature Microbiology, 4, DOI: 10.1038/s41564-019-0437-2