Sphingomyelinase-mediated bacterial extracellular vesicle

Renowned for their role in pathogenesis, bacterial extracellular vesicles (EVs) are increasingly recognized for their contributions to bacterial physiology. Here, we investigate EV secretion dynamics and EV stability under nutrient-rich and nutrient-limited bacterial growth conditions. Unexpectedly, we find that in nutrient-rich environments, EVs are actively degraded in the extracellular milieu. This process is driven by the concurrently secreted sphingomyelinase (SMase), uncovering a previously unrecognized enzymatic role beyond virulence. Lipidomic profiling reveals that SMase-mediated degradation is dependent on a sphingolipid-rich EV lipidome, which only occurs in nutrient-rich cultivation conditions. The essential role of SMase in EV degradation is confirmed through three independent approaches: exogenous SMase addition, pharmacological inhibition, and a sphingomyelinase knockout mutant. Multi-omic profiling of EVs further reveals that under nutrient limitation, only degradable EVs support bacterial growth, indicating that EVs can function as nutrient reservoirs. Our findings establish a mechanistic link between EV composition, EV function, and SMase-mediated EV degradation, and offer insights into how bacteria can repurpose and recycle vesicle components under nutrient limited conditions.