Discovery of the key to the success of some of the most virulent bacteria

Image: DNA horizontal transmission between two cells of bacteria Escherichia coli. Image: Antonio Juárez (IBEC)

Researchers at the Institut de Bioingenieria de Catalunya (IBEC), the Institute for Research in Biomedicine (IRB Barcelona) and the University of Barcelona (UB) have discovered the strategy adopted by enterobacteria to facilitate the incorporation and regulation of genes that confer resistance and virulence. Published recently in PLoS Genetics, the study opens up the way to the development of new drugs that will allow treatment of the infections caused by multi-resistant variants of pathogens such as Escherichia coli, Salmonella and Shigella.

Bacteria that belong to Enterobacteriaceae cause intestinal infections such as dysentery and typhus, and extra-intestinal ones such as urinary infections, meningitis and septicemia. Many of the genes associated with bacterial pathogenicity are acquired by horizontal transfer (HGT), which implies that they can be transferred from one bacterial cell to another, and even from an individual of a distinct species, within the same generation. “It is like your neighbour passing you genes that are favourable under given circumstances,” explains Miquel Pons, researcher at IRB Barcelona and professor of the UB. The acquisition of DNA through horizontal transfer can involve the incorporation of new properties and therefore the capacity to adapt to new environments. Among these properties, special emphasis is placed on resistance to antibiotics and other antimicrobial substances, and on virulence factors, that is to say, the genes that allow bacteria to cause infectious diseases.

“Although we are aware to the relevance of HGT in the variability of bacterial genomes, little is known about the mechanisms that allow the new fragments of DNA acquired to be beneficial for the cell receptor,” explains the coordinator of the study, Antonio Juárez, researcher at IBEC and professor of microbiology at the UB. This new study demonstrates that Enterobacteriaceae have developed a mechanism to facilitate the acquisition of DNA by HGT. This mechanism involves the production of two proteins, H-NS and Hha, which react together and also with bacterial DNA, and facilitate the integration of the new genetic material into the receptor cell and specifically regulate this information. The researchers propose interfering with the expression of virulence factors and antibiotic resistance, functions that are often determined in this type of genetic material, by altering these two proteins. Juárez concludes that “this study opens up a new approach to combat bacteria that is not based on destroying them but on attacking and deactivating the very mechanism that makes them harmful.”

Reference article:
Differential Regulation of Horizontally Acquired and Core Genome Genes by the Bacterial Modulator H-NS. Rosa C. Baños, Aitziber Vivero, Sonia Aznar, Jesús García, Miquel Pons, Cristina Madrid, Antonio Juárez. PLoS Genetics (June 2009), Vol 5, Issue 6, e1000513