GARCIA DE LOS SANTOS, ALEJANDRO

Alejandro García-de los Santos, PhD
Full time assistant Professor

In 1989, I joined the Nitrogen Fixation Research Center, which later evolved into the Center for Genomic Sciences in the genomic era. During this time, I had the opportunity to work with Susana Brom, who was an Assistant Professor, on a significant topic: bacterial genomic plasticity. Our initial study model was the bacterium Rhizobium etli CFN42, a facultative diazotroph that forms a mutualistic relationship with leguminous plants. Its genome consists of one chromosome and six plasmids (ranging from 180 to 600 kb), with multiple repeated regions scattered throughout, making it an ideal model for studying genomic plasticity.
We discovered that the loss of plasmids in vitro occurs frequently, contributing to the genomic plasticity of this bacterium. This led us to propose research focused on systematically reducing the extra-chromosomal genome to identify the functions of these replicons. A key finding was that some plasmids contain enzymes involved in primary metabolism, which is rare in most bacteria. This research has improved our understanding of genomic plasticity, the relationship between chromosomes and plasmids, and their roles in saprophytic life and symbiosis with host plants.
Currently, we are utilizing genome mining to identify the genetic and genomic factors that enable bacteria of the order Rhizobiales to adapt to high concentrations of Cu(I). Our analysis has revealed two key genomic characteristics in members of Rhizobiales that are absent in well-known homeostasis model genomes, such as Escherichia coli.
The first is the presence of multiple copA genes, up to 5 per genome, which encode different Cu(I)-ATPases (PMC5552934). The second is the co-occurrence of genes for resistance to various metals (Cu, Ni, Co, Zn, Cd) at the same location, which we call Multimetal Homeostasis Gene Clusters (MHGC). Some of these clusters show potential mobility. This organization of resistance genes at a single location, such as MHGCs, is likely part of an evolutionary process that leads to microorganisms developing resistance to multiple antimicrobials.
Due to bacterial resistance to multiple antimicrobials and the clinical use of Cu(I)'s bactericidal properties, there is significant interest in studying the composition, evolution, and dispersal mechanisms of bacterial resistomes in microorganisms with various lifestyles.