Bacteria employ various mechanisms to inhibit the growth of competitors in their environment. One example of this is the Type VI secretion system (T6SS), a multiprotein nanomachine that propels a spear-like structure to pierce the envelopes of adjacent target cells and enable delivery of toxic T6SS-associated effector proteins. Many T6SS-deploying bacteria utilize Type VI lipase effector (Tle) proteins to destabilize the phospholipid bilayers of target cells, while simultaneously synthesizing Type VI lipase immunity (Tli) proteins to neutralize Tle delivered from kin.My thesis focuses on a Tle-Tli pair from the coliform species Enterobacter cloacae. In Chapter II, I show that Tle is inactive when delivered by inhibitor cells that do not express its cognate Tli protein. This is the first described instance of a T6SS effector that is activated by its immunity protein. I present further data in Chapter III showing that the nature of this activation is a cross-link that forms when a specific arginine-lysine pair within Tle reacts with the alpha-dicarbonyl compound methylglyoxal. The resulting cross-link is an example of an advanced glycation end-product (AGE). The formation of AGEs in proteins is known to be a slow, spontaneous process and has previously been associated with numerous degenerative diseases including atherosclerosis and type 2 diabetes. In Chapter IV, I show evidence that similar activation mechanisms occur in Tle homologs from Serratia marcescens and Dickeya dadantii. The AGE crosslink responsible for activating Tle forms with a speed and specificity that is atypical for these reactions and is the first example of an AGE structure being necessary for protein function. Therefore, the Tli-dependent activation of Tle in E. cloacae and its homologs may serve to deepen the current understanding of AGEs.