Research

What we do?

Broadly speaking, our group works on the evolution of clinically relevant bacteria. In other words, we try to:

characterise the genetic and phenotypic diversity in disease-causing bacteria,
understand the main driving forces behind the emergence of such diversity, and
quantify the impact of this process on bacterial populations.

Why is it important?

What we do has a direct implication for the society for two main reasons.

First, a good understanding of the microbial population dynamics is important for the rational design of vaccine and antibiotic use to minimise the disease burden in the short- and the long-term.

Second, understanding where the microbial diversity comes from and how it is generated can help us predict antibacterial drug targets and novel classes of drugs which minimise the rise of bacterial resistance against such treatments.

Main research areas

Evolution of bacterial sugars

Bacterial cell surfaces are surrounded by glycans (sugars), including the highly diverse capsules or lipopolysaccharides/O-antigens. Given that these structures have proved good vaccine targets in respiratory bacterial pathogens (Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis), and that we are rapidly running out of antibiotics, there have been many discussions about fighting Gram-negative antibiotic-resistant bacteria by producing new, capsule-targeting approaches (e.g., glycoconjugate vaccines, immunotherapies, phage-derived enzymes, treating infections with live phages, etc.). However, genetic loci which synthesise capsules are diversity-generating machines, and the implications of the use of such approaches against highly versatile Gram-negatives are unclear. In our lab, we study the diversity and evolution of bacterial capsules using big data genomics and try to construct better conceptional models of how bacterial capsules evolve and what it means for the design of new medical interventions.

Bacteria-phage interactions

The diversity of the bacterial polysaccharide capsules is a fascinating problem in biology. The Red Queen Hypothesis predicts that rapid generation of diversity may be the result of antagonistic interactions where constant evolutionary innovation is necessary to adapt to the ever-changing co-evolving fitness landscape. One possible explanation for the capsule diversity would thus be a co-evolutionary arms race with bacterial viruses – bacteriophages or phages. Phages are known to carry specific enzymes called depolymerases (usually in their tail fibers) that are specific to different capsule types. Experimental studies feature beautiful examples of reciprocal co-evolutionary changes in polysaccharides and phage tail proteins. However, it is not clear whether co-evolution between bacteria and phages is the reason behind diversity of capsules and tails. In our lab, we tackle this question by making sense of the currently observed bacterial and phage diversity and using computer simulations to reconstruct how it has emerged.

Bacterial sex and adaptation

Bacteria have an enormous capacity for exchanging their DNA horizontally. This can happen via several different mechanisms (e.g., passing on DNA directly via conjugation, acquiring it from the environment via transformation, using phages as a third party), but ultimately all of them are a form of ‘bacterial sex’ and enable rapid evolutionary adaptation via genetic innovation. However, bacterial sex is a process which can be optimised as too little sex can be as bad as too much sex (most innovation is bad, some is good). Optimisation of this problem depends on the biology of the species in question, interactions with other species, the ecology and many other variables. In our lab we employ genomic and bioinformatic tools to quantify bacterial sex in different species, like Streptococcus pneumoniae, Klebsiella pneumoniae or Escherichia coli, and understand what this means for bacterial evolution.

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