ITQB: BCB - PhD Theses
URI permanente para esta coleção:
Navegar
Entradas recentes
A mostrar 1 - 9 de 9
- New approaches to study Staphylococcus aureus elongation and divisionPublication . Francisco Da Costa, Sara; Hensel, Zach; Pinho, MarianaBacterial cell division has predominantly been studied in rod-shaped model bacteria such as Escherichia coli (a gram-negative bacterium) and Bacillus subtilis (a gram-positive bacterium). However, organisms with different morphologies may possess distinct types of regulation for vital processes, such as growth and division. Therefore, understanding distinct mechanisms regulating these processes becomes particularly significant, especially for clinically relevant bacteria such as Staphylococcus aureus.
- New insights into Staphylococcus aureus cell cycle and cell wall stress responsePublication . Fernandes, P.B.; Pinho, Mariana Gomes de" The Gram-positive Staphylococcus aureus is considered one of the most prominent pathogens worldwide, presenting a global health concern. Particularly, the multi-drug resistant methicillin- resistant S. aureus (MRSA) is well known for causing nosocomial infections, as well as across the community. S. aureus capacity to survive antibiotic treatment, which makes MRSA infections very difficult to treat, prompts the need for further studies of its biology, so that new approaches for treatment can be devised. (...)"
- Studies of Staphylococcus aureus’ cell cycle: New approaches for automated analysisPublication . Saraiva, Bruno Manuel Santos; Pinho, Mariana; Henriques, Ricardo; Fernandes, Fábio"Infections by antibiotic resistant bacteria are a rising problem in today’s world health and are expected to become a major cause of death over the next decades. Staphylococcus aureus is a gram-positive bacterium that is often associated with antibiotic resistant infections. In order to find new strategies to deal with this type of infections, it is important to better understand how bacteria regulate their cell cycle. The study of cell cycle regulation is an understudied field in most bacteria, and it is of particular interest in pathogens such as S. aureus. We imaged by widefield fluorescence microscopy a mutant library containing a transposon insertion in virtually every non-essential gene of S. aureus, to find new key players involved in cell cycle regulation."
- Mechanisms coordinating peptidoglycan synthesis with the cell cycle in Staphylococcus aureusPublication . Monteiro, João Miguel da Silva Queiroga; Pinho, Mariana Gomes de"The emergence and spread of antibiotic resistance in bacteria constitutes one of the major challenges to global public health and is predicted to further escalate during the 21st century. One of the most frequent multi-drug resistant pathogens is methicillin-resistant Staphylococcus aureus (MRSA), a gram-positive coccoid bacterium that causes difficult to treat infections with severe morbidity and mortality rates. Many of the commonly used antibiotics target steps in the biosynthesis of peptidoglycan (PG), a robust but flexible meshlike macromolecule that withstands the intense internal turgor in the cell, among other functions. The integrity of the PG layer is of the utmost importance to bacteria, which must ensure that incorporation of new PG strands and remodelling of the existing ones is timely coordinated with the progression of the cell cycle. Despite its clinical relevance, many fundamental biological processes in S. aureus remain to be elucidated.(...)".
- Determination of cell shape in Staphylococcus aureusPublication . Tavares, Andreia Filipa Campos; Pinho, Mariana Gomes de"Cell size and morphology are two extremely important characteristics in the adaptation of bacteria to the external environment and are often associated to bacterial survival and growth. In Staphylococcus aureus, a common colonizer of human skin and mucus membranes, the small spherical shape of cells may be an advantage during colonization, helping this pathogen to evade host immune system. The fact that cell shape is maintained over consecutive generations evidences the existence of tightly regulated underlying mechanisms. Bacterial shape is maintained by the existence of an external cell wall mainly composed of peptidoglycan (PGN), a mesh-like molecule made by glycan chains cross-linked by short peptide bridges. Localization of PGN synthesis is dependent on the action of cytoskeletal proteins, which direct the activity of proteins involved in this synthesis, including Penicillin-Binding Proteins (PBPs) and proteins from the shape, elongation, division and sporulation (SEDS) family, to specific regions of the cells. T(...)"
- Cell Division and morphogenesis in Staphylococcus aureusPublication . Pereira, Ana Raquel Ramos; Pinho, MarianaThe cell shape is such a distinctive characteristic of bacteria that it has been used extensively for their classification. In most bacteria, cell shape is sustained by peptidoglycan, a macromolecular polymer that surrounds the cell conferring mechanical strength and protecting the cell from lysing from high turgor pressure. The ability of bacteria to faithfully maintain morphology in a population and to pass it on to the next generation suggests the existence of molecular mechanisms that control morphogenesis. (...)
- Peptidoglycan assembly machines: The Staphylococcus aureus Penicillin-Binding ProteinsPublication . Pereira, Pedro Matos; Pinho, Mariana GomesThe bacterial cell wall (CW) is of critical importance to cell viability. Impairment of CW synthesis or integrity rapidly leads to cell lysis and death. As there is no equivalent structure to the bacterial CW in mammalian cells, many important antibiotics target the enzymes responsible for its synthesis. The scaffold of the CW consists of the polymer peptidoglycan (PGN), a meshlike structure composed of glycan strands cross‐linked by short peptides. The final steps of PGN synthesis are catalysed by the penicillin‐binding proteins (PBPs), which assemble lipid‐linked disaccharide peptide precursors of PGN into high molecular weight oligomers via transglycosylation and transpeptidation reactions. These proteins have been proposed to work in multi‐enzyme complexes that would also include CW hydrolases.(...)
- Cell division and chromosome segregation in Staphylococcus aureusPublication . Veiga, Helena Maria PintoBacterial cell division by binary fission involves several essential steps. Initially, the mother cell duplicates in size and replicates its DNA, in preparation for division. As the new sister chromosomes are synthesized, they are progressively segregated to the future daughter cells and once the division site is cleared of the majority of chromosomal DNA, the division septum starts assembling. The complete septum then constricts and, ultimately, the mother cell splits into two identical daughters. The generation of equal, viable progeny is strictly dependent on the regulation and coordination of these processes, both in space and in time. It is particularly important that the division septum is properly positioned at midcell and that chromosome segregation and cell division are synchronized, to prevent fragmentation of the genome by septum closure over the nucleoid.
- Insights into cell wall synthesis and cell division in Staphylococcus aureusPublication . Jorge, Ana Maria; Pinho, Mariana G.Staphylococcus aureus is a gram-positive bacterial pathogen that besides persistently colonizing healthy individuals, is responsible for a large number of hospital-associated bacterial infections. The extraordinary capacity of S. aureus to acquire resistance to antibiotics led to the emergence of highly resistant strains, mainly methicillin-resistant S. aureus (MRSA) strains, that are a major cause of soft skin and tissue infections and bacteremia. In one third of European countries, including Portugal, more than 25% of S. aureus infections are caused by MRSA strains. The capacity of MRSA strains to resist β-lactam antibiotics (such as penicillin) is mainly due to the acquisition of an extra-species penicillin-binding protein (PBP), PBP2A. PBPs are bacterial enzymes involved in the synthesis of the cell wall polymer peptidoglycan. Besides PBP2A, which is present only in MRSA strains, S. aureus has 4 native PBPs (PBP1-4), which catalyze the polymerization (transglycosylation) and the cross-linking (transpeptidation) of glycan chains, forming a strong yet flexible structure that protects the cell from the high internal osmotic pressure. Peptidoglycan is unique to the bacterial kingdom and its biosynthesis is the target of a vast number of clinically important antibiotics such as β-lactams and glycopeptides. β-lactam antibiotics target the transpeptidase domain of PBPs, halting peptidoglycan synthesis and eventually leading to cell lysis. However, in MRSA strains the existence of PBP2A, which has a low affinity for β-lactams, enables cell wall synthesis to continue even in the presence of these antibiotics. Under these conditions, the transpeptidase domain of PBP2A functionally cooperates with the transglycosylase domain of the unique bifunctional PBP, PBP2, to ensure continued cell wall synthesis and cell survival.(...)