As predominant intestinal symbiotic bacteria, Bacteroides are essential in maintaining the health of the normal mammalian host; in return, the host provides a niche with plentiful nutrients for the symbionts. However, the intestinal environment is replete with chemical, physical, and biological challenges that require mechanisms for prompt and adept sensing of and responses to stress if the bacteria are to survive. Herein we propose that to persist in the intestine Bacteroides take advantage of their unusual bacterial sphingolipids to mediate signaling pathways previously known to be available only to higher organisms. Sphingolipids convey diverse signal transduction and stress response pathways and have profound physiological impacts demonstrated in a variety of eukaryotic cell types. We propose a mechanism by which the formation of specific sphingolipid membrane microdomains initiates signaling cascades that facilitate survival strategies within the bacteria. Our preliminary data suggest that sphingolipid signaling plays an important role in Bacteroides physiology, enabling these bacteria to persist in the intestine and to perform other functions related to symbiosis. stress response | bacterial sphingolipids | lipid rafts T he Bacteroides species make up a predominant genus of bacteria residing within the mammalian intestine. Organisms belonging to this genus have been the subject of extensive research and possess many distinctive features contributing to their ability to flourish in the intestine. For example, Bacteroides have sophisticated ability to degrade polysaccharides (for energy acquisition) (1), pronounced phase variation in surface polysaccharide synthesis (for antigenic versatility) (2, 3), and extensive surface decoration with host glycans (for molecular mimicry) (4). These bacteria display another extremely rare structural feature that has been recognized for decades but remains largely unstudied: membrane sphingolipids. Sphingolipids were generally thought to exist exclusively in eukaryotes until they were discovered in a handful of bacterial and viral lineages (5, 6). What is the function of sphingolipids in bacteria? Are they important in maintaining Bacteroides in their ecological niches? Herein we provide first evidence supporting an important role for sphingolipids in the ability of Bacteroides to survive stress, and we discuss the potential role of sphingolipids in maintaining intestinal symbiotic bacterial populations.
Results and DiscussionAre Sphingolipids Important for Bacteroides Growth? Sphingolipids are characterized by an aliphatic amino alcohol sphingoid backbone called long-chain base (LCB). LCB is attached via an amide bond to a fatty acid and via an ester linkage to a polar head group (Fig. 1A). Sphingolipids are always present in eukaryotic cells but are absent in most bacteria, whose membranes comprise only glycerol-based phospholipids (Fig. 1B). However, a few bacterial species possess both phospholipids and sphingolipids. These sphingolipid-containing bacteria are highly r...