Investigating the Function of a Klebsiella pneumoniae Microcin

Klebsiella pneumoniae (Kp) is a major cause of bloodstream infections and sepsis in newborns in low- and middle-income countries. However, the mechanisms by which Kp strains cause these infections remain poorly understood. Prior computational analyses performed in our lab identified genes enabling Kp strains to produce a microcin, a small protein bacteria use to kill their competitors. We found that these genes were more prevalent in Kp strains causing early-onset sepsis, which generally results from bacteria transferred from mother to newborn during birth. We also identified these genes in Kp from the gut microbiome of mothers in the same study. Early experiments show that this microcin allows Kp to kill other Klebsiella bacteria in low-iron conditions, similar to the human gut, where Kp commonly resides. This suggests that the microcin may provide Kp strains a growth advantage, potentially increasing their likelihood of being passed from mother to newborn. In my research, I will investigate whether gut-mimicking conditions influence microcin production, and identify how this microcin kills other bacteria. First, I will test whether gut-like conditions beyond low-iron, such as reduced oxygen, and specific gut nutrients, increase microcin activity. I will then use transcriptomic analyses to determine whether these conditions alter microcin gene expression. Second, I will generate and screen a collection of thousands of Kp mutants to identify the bacterial surface receptors the microcin targets. Studying the regulation and function of this microcin may reveal how Kp strains spread more efficiently from mothers to newborns. This knowledge may inform strategies to reduce harmful maternal Kp gut carriage, potentially lowering the rates of neonatal sepsis caused by Kp.