Our project seeks to revolutionize our understanding of bacterial genetics by investigating the occurrence, regulation, and function of adenosine-to-inosine (A-to-I) mRNA editing in bacteria. Traditionally, bacteria have been viewed as haploid organisms whose genetic potential is fixed, unable to diversify their proteome through mechanisms such as alternative splicing. However, recent discoveries—including our own—suggest that bacteria might generate alternative protein isoforms by editing their messenger RNA, thereby introducing functional diversity at both the single-cell and population level.
We hypothesized that A-to-I mRNA editing modifies the protein-coding sequence post-transcriptionally, enabling the bacterial ribosome to translate one gene into multiple protein isoforms with distinct activities. This process appears to be regulated by environmental cues and may serve as a flexible adaptive strategy, allowing bacteria to rapidly respond to fluctuating conditions and stressors such as nutrient deprivation or antibiotic exposure. Through this mechanism, bacteria may introduce what is essentially “pseudo-heterozygosity,” conferring advantages in survival and competition that were previously unrecognized in these organisms.
The overall objectives of the project are threefold:
• To systematically identify and catalog mRNA editing events in diverse bacterial species and under varied environmental conditions, using both existing RNA-seq datasets and newly developed laboratory protocols.
• To elucidate the genetic and biochemical mechanisms that regulate these editing events, focusing on sequence motifs, enzyme-substrate relationships, and environmental triggers.
• To determine the functional significance of mRNA editing for bacterial physiology, including its impacts on growth, adaptation, antibiotic resistance, and pathogenicity.
By addressing these objectives, the project aims to make a foundational impact on bacterial genetics, overturning established dogma and providing new explanations for elements of bacterial adaptation that remain poorly understood. The expected significance of these findings extends beyond basic science, offering new insights into infection biology, antibiotic resistance mechanisms, and potential avenues for diagnostic and therapeutic innovation in biomedicine. The research also promises to deliver valuable tools and datasets to the wider scientific community, thereby enabling broader exploration of RNA-level regulation in bacteria.
Overall, the project sets the scene for a paradigm shift in how bacterial diversity and adaptability are conceptualized and studied, with direct implications for public health, microbiology, and biotechnology.
