The ability of bacteria to take a record of previous threats to its fitness via the uptake of some of the genetic material of the offender—known as its immunological memory—allows it to survive future attacks. Bacteria can gain this historical information via genetic exchange with other bacteria, as well—but the process of gene transfer itself can disrupt the rest of the genome. Thus, the very mechanism that protects bacteria—conferring resistance to antibiotics, novel virulence traits, or microbial defense tools—can also disturb future interactions of the cell's DNA with its machinery.
“The acquisition of these genes has the potential to disrupt several regions of the genome, affecting several functions of the cell, as well as its competitiveness,” writes Pedro Oliveira, Ph.D., of the Pasteur Institute in Paris, to GEN. Dr. Oliveira is the lead author of a new study examining the fitness cost of chromosomal integration in bacteria. “Consequently, the adaptation of bacteria lies in a conflict between the advantages of acquiring genes to adapt and the need to maintain the cohesion of their genome.”
When bacteria accept new genetic material into their genomes, the gene shuffling usually occurs in a specific location, which Dr. Oliveira and his other colleagues from the Pasteur Institute in Paris identify as recombination hotspots. The authors assert in their study, published on October 10, 2017 in Nature Communications (“The Chromosomal Organization of Horizontal Gene Transfer in Bacteria”) that the organization of new genetic material into these common areas is both a gift and a curse. There is a careful balancing act associated with the addition of new genetic material, and the bacteria have to carefully weigh the need to acquire new information and the need to keep the genome organized. While these hotspots are “treasure troves of the novel functions that are responsible for bacterial evolution,” say the researchers, their existence adds chaos to the genomic snapshot, as the information at the hotspots is constantly in flux.
The authors wanted to determine how abundant these hotspots are, where they are located, what genetic material they contain, and what features are required to classify these sites as hotspots. They analyzed 932 genomes representing 80 different bacterial species (including the most important human pathogens, such as meningitis, cholera, etc.) and examined where genetic changes were taking place within said genomes. They found that across the 80 bacterial species of interest, the incorporation of new genomic material was concentrated in ~1% of the chromosomal regions.
“In a nutshell, we found that almost all bacteria make use of dedicated ‘reservoirs’ dispersed throughout the genome…to accommodate the flow of incoming genetic information,” notes Oliveira to GEN. The hotspots are representative of many of the adaptive traits of the genome; hotspots are areas that “undergo frequent renovation by genetic turnover,” according to Oliveira.
While Dr. Oliveira says his team's work on horizontal gene transfer in bacteria does not directly link to CRISPR/Cas9, he comments that by accurately mapping these hotspots at a genome-wide scale, researchers can probably use such gene-editing techniques to decrease or shut down the activity of these regions. Ultimately, says Oliveira, this could allow for the reduction in the ability of bacteria to acquire information that could potentially be harmful to humans (such as genes associated with antibiotic resistance, new virulence, and bacterial defense mechanisms). He adds that future work on hotspots should focus on the fate of these regions, how long they are able to persist in the face of constant renovation, and what factors lead to the demise or disappearance of a hotspot within a genome.