Genome dynamics in major bacterial pathogens

Abstract

Pathogenic bacteria continuously encounter multiple forms of stress in their hostile environments, which leads to DNA damage. With the new insight into biology offered by genome sequences, the elucidation of the gene content encoding proteins provides clues toward understanding the microbial lifestyle related to habitat and niche. Campylobacter jejuni, Haemophilus influenzae, Helicobacter pylori, Mycobacterium tuberculosis, the pathogenic Neisseria, Streptococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus are major human pathogens causing detrimental morbidity and mortality at a global scale. An algorithm for the clustering of orthologs was established in order to identify whether orthologs of selected genes were present or absent in the genomes of the pathogenic bacteria under study. Based on the known genes for the various functions and their orthologs in selected pathogenic bacteria, an overview of the presence of the different types of genes was created. In this context, we focus on selected processes enabling genome dynamics in these particular pathogens, namely DNA repair, recombination and horizontal gene transfer. An understanding of the precise molecular functions of the enzymes participating in DNA metabolism and their importance in the maintenance of bacterial genome integrity has also, in recent years, indicated a future role for these enzymes as targets for therapeutic intervention.

Fig. 1

Phylogenetic map based on 16S rRNA gene sequences of the bacterial species under study.

Fig. 2

DNA repair, recombination and replication (3R) are essential processes in living cells. These processes are interconnected, often sharing components to restore or replicate genetic information. A growing body of evidence is pointing at the necessity of harboring 3R mechanisms for pathogens to effectively colonize their human host, which exerts, among others, oxidative stress on the bacterial genomes through the oxidative burst (described in the main text). Also, the host relies on 3R mechanisms to survive an invasion of potentially deadly organisms. Bacteria or bacterial components, as well as the inflammation process triggered by the bacteria, may induce host DNA damage (Box 1). The outcome of a bacterial invasion depends on both the host and the pathogen: they are not static players independent of each other. This interaction is best described as an interplay where the actions of one affects the other, for better or for worse. One example illustrating this scenario is the effect of antibiotics; although helping the host to clear the invading pathogen, induction of bacterial DNA repair mechanisms triggered by the antibiotic may lead to the dissemination of bacterial virulence determinants (Box 2).

Fig. 3

Model of the meningococcal transformation machinery based on the current information on the components involved in this process. DNA is predicted to enter the meningococcal cell through the PilQ pore, which, when it is wound around the pilus rod, sterically just allows the DNA to enter the cell. This hypothesis needs to be biologically verified.