Akorede L. Seriki
Faculty Advisor: Christopher J. Marx
Learning from Bacteria; The Same, Yet Different
Formaldehyde is an extremely toxic compound to virtually all organisms due to its ability to react nonspecifically with proteins and nucleic acids. It is lethal at high concentrations; thus, it is important to understand how organisms respond to its toxicity.
Methylotrophic bacteria represent an ideal model system for understanding formaldehyde toxicity. This is because methylotrophs can use substrates with a single carbon – such as methanol – for growth and energy, during which formaldehyde is produced as a central metabolic intermediate. To understand the coping strategies used by methylotrophic bacteria to mitigate metabolic toxicity (tolerance), we invoke the concept of Phenotypic Heterogeneity. It has been shown that within a single bacterial culture of the Methlyorubrum extorquens grown under various concentrations of formaldehyde, a minority population of cells grow normally (tolerant population) while another subset loses viability (sensitive population). Interestingly, this tolerance is inherited by subsequent generations independent of changes within the genome. Indeed, the absence of a genomic basis for these diverse phenotypic outcomes is a case of phenotypic heterogeneity, and investigating the mechanistic underpinning of this heterogeneity is warranted. We have so far identified 23 genes that appear to be relevant to the success of formaldehyde tolerant populations. Of these genes, 22% (4 Heat shock proteins; Hsp20, and 1 Universal Stress protein; UspA) are involved in protein misfolding.
We hypothesize that the expression of these genes increases the ability of cells to handle protein misfolding, thus contributing to formaldehyde tolerance. To this end, we are generating genetically modified strains of M. extorquens to explore the heterogenous nature of gene expression patterns of these genes that contribute to phenotype diversity.
Unraveling the mechanisms underlying the variation in phenotypic responses in genetically identical bacteria populations will expand our knowledge of the behavioral responses of bacteria to environmental stress factors.
Funding: DOE and NSF