UGA scientists have recently published the first complete atlas of bacterial serine-threonine kinases. This innovative resource has the potential to unlock essential new insights for designing new antibiotics. Brady O’Boyle, who is co-leading this groundbreaking study published in the journal Science Signaling. This research characterizes and assigns functions to more than 300,000 kinase sequences collected from about 26,000 bacterial strains. This major research reveals the evolutionary secrets of these enzymes. It also underscores their potential vulnerability as targets for new antimicrobial drugs.
The research carried out within this approach is specially aiming for the structural-functional diversity of bacterial serine-threonine kinases. O’Boyle and his lab had an exciting realization: the number of kinases differs widely between species. Whereas some strains have as few as one kinase present, others—most notably those in the Actinobacteria genus—contain more than 60. Such variability highlights how complex bacterial biology is and is indicative of differential evolutionary pressures on different bacterial lineages.
Comprehensive Classification of Kinases
Brady O’Boyle and his coworkers rolled up their sleeves and dug into the classification efforts for the bacterial STKs. Within these, they further divided the families into pseudokinase and kinase groups due to shared catalytic domain similarities. In addition to providing a resource for RNAi experiments, this classification represents an important step toward a deeper understanding of kinase evolution and function.
To get started, the team used the National Center for Biotechnology Information’s reference sequence (RefSeq) database to sift through and compile their data. They were able to analyze a million-molecule array of sequences at once. During this process, their work led to a rich compendium that deepens our understanding of individual kinases and begins to uncover wider trends in bacterial evolution. The breadth of this study can offer an invaluable resource for any scientist looking to improve their understanding of kinase biology.
Implications for Antibiotic Development
The implications of this study go beyond intellectual curiosity. O’Boyle and his colleagues suggest that targeting druggable sites within bacterial serine-threonine kinases could lead to innovative strategies for combating antibiotic resistance. With each new antibiotic, we are always one step behind mutant bacteria that seem to evolve power shields of resistance. Researchers are focusing their efforts on these kinases. In doing so, they may be able to discover novel ways to stop bacterial growth, sidestepping the resistance patterns found in traditional antibiotics.
One outstanding application highlighted by O’Boyle and his team is the ability to tackle the tuberculosis bacterium. Treating this chronic infection is no simple matter. Though there are no immediate therapeutic implications from the atlas, new insights may fuel novel therapeutic strategies. Our research underscores the massive body of work that has been performed on eukaryotic kinases. Finally, it stresses that bacterial kinases have special properties that warrant deeper exploration.
A Resource for Future Research
Asserine-threonine kinases atlas, an important step toward advancing microbiology and antibiotic discovery. O’Boyle’s research provides an in-depth look at these enzymes. This paradigm-shifting work unlocks new avenues of inquiry in fundamental biology and clinical application.
We invite future researchers to use this massive compendium to conduct specific searches for kinases involved in pathogenicity or antibiotic resistance. At times, the differences between bacterial and eukaryotic kinases mimic the likenesses. This targeted understanding will help us to reevaluate existing therapeutic paradigms and inspire novel small-molecule design approaches.