Research Interests

Bacterial cells are surrounded by a tough but flexible cell wall, which can be considered as an armour-like structure, that defines the shape of bacteria and confers protection against various external assaults (see Figure 1).

The bacterial cell wall of S. aureus, and other Gram-positive bacteria, has a diverse composition that includes proteins, glycopolymers (such as wall teichoic acids and/or capsular polysaccharides) and its major component, the peptidoglycan, a macromolecule, also known as murein, that is present in most bacteria.

Peptidoglycan is absolutely essential for bacterial survival and its synthesis is the target of different classes of antibiotics, including the well known penicillin. It is a macromolecule made of chains of disaccharides of two particular sugars, N-acetylglucosamine and N-acetylmuramic acid, linked through oligopeptides. The peptide composition of the oligopeptides, also known as peptidoglycan stem peptides, includes D-aminoacids and varies between bacterial species (see Figure 2).

Perhaps because peptidoglycan is common to most bacteria, organisms that can be infected by bacteria rely on peptidoglycan-binding proteins to detect and signal the presence of invading bacteria. Peptidoglycan is therefore a telltale molecule that signals bacterial presence in an infected host, and whose recognition leads to an innate immune reaction that culminates in the elimination of these microorganisms. Therefore, bacteria have to “hide” their peptidoglycan from the host, during all stages of their cell cycle, in order to avoid detection by the innate immune system.

Because bacterial cell division is a complex process, that involves not only the synthesis of new cell surface, but also the synthesis of a division septum or the replication, and subsequent segregation, of the chromosome, a bacterial cell has to ensure that the new cell surface is assembled in the right place and at the right time, to avoid peptidoglycan exposure at the cell surface (see Figure 3):

1)    Localization of the cell wall assembly machine at the middle of the cell.

2)    Initial phase of synthesis of the bacterial cell wall at the division septum.

3)    Late phase of synthesis of cell wall at the division septum.

4)    Maturation of the cell wall, which is not accessible for external recognition, before separation of the two new daughter cells.

5)    Splitting of the two daughter cells which exposes the new cell wall to the surrounding medium.

In the Bacterial Cell Surfaces and Pathogenesis laboratory we are addressing four main questions that represent the different research lines being followed:

1. Can the aminoacid composition of the bacterial peptidoglycan interfere with its recognition by the host?
2. Does peptidoglycan metabolism during the entire cell cycle influences its recognition by the host?
3. Are bacterial polysaccharides, namely those that are linked to the bacterial surface, capable of interfering with peptidoglycan recognition?
4. How can bacteria hide the inflammatory peptidoglycan macromolecule?

To answer these questions, we mainly use, as model organisms, two Gram-positive bacterial pathogens Staphylococcus aureus and Streptococcus pneumoniae:

S. pneumoniae is a major community acquired pathogen capable of causing life-threatening diseases and a major cause for bacterial meningitis, a disease with high morbidity and mortality worldwide, despite the implementation of several vaccination programs and antimicrobial agents.

S. aureus is a Gram-positive bacterium that can cause a variety of serious illnesses, such as bacteremia, pneumonia, endocarditis or septic shock. Importantly, antibiotic resistant strains are currently a serious problem in the clinical setting and, more recently, in the community.