Grant: Operating Grant

Infections cause severe illness and death in newborn babies much more commonly than in adults. One of these infections is caused by a bacterium called Listeria monocytogenes (Listeria). The reason for this increased risk of newborns to suffer and die from Listeria is only partially understood. In our ongoing work aimed at finding out why newborn babies are at such high risk, we looked at 40,000 possible differences between the responses of newborns vs. adults to Listeria infection. We found that infected newborn cells made much less than the adult of one particular protein called guanylate binding protein 1, or GBP1. In adult mice this protein is known to be essential for protection from infection with Listeria, suggesting our finding with human newborn cells might be very important. The role of this and similar GBP proteins for protection from infection has never been studied at all in human newborns. We found that the level of GBP1 produced closely mimics how well the human cells infected with Listeria do, i.e. if there is more GBP1 they kill the bacteria better and resist the attack, but if there is less GBP1, they succumb to infection with Listeria and die. In this proposal we will determine the precise role played by GBP1 in protection vs. susceptibility of human cells to severe infection with Listeria. We will also identify the reason why the newborn makes less GBP1, as the first step toward finding ways to increase production of GBP1 and protect newborns better. Given the central role this type of protein is known to have for protection of mice against from other infections that are known to cause severe infection in human newborns, what we will find out will possibly be important for many of these newborn infections as well.