by Roberto
Fig. 1. Structure of LPS. Source. Frontispiece: Schematic of LPS. Source
The O-side chains of lipopolysaccharides (LPS), the outermost feature of most Gram-negative's outer membrane, are highly variable in terms of their chain length and chemical composition. In my last post, I described how the O-side chains of some bacterial strains serve as a settlement and metamorphosis cue for a marine invertebrate. My thoughts immediately took me to this question: What was the early evolutionary history of O-side chain variability? The presence of the side chain does make the outer membrane less permeable, suggesting a primordial function. But why the variability and since when? Given that I didn't come up with an answer quickly, I thought "Talmudic Question." But soon enough, I came up with a feasible answer. So, no Talmudic Question after all. Here's how my thinking evolved...
Because the O-side chain from bacterial pathogens usually elicits antibody production it is most often called the "O-antigen" and serves as a key determinant for the serotyping of strains. It is no surprise that we usually teach our students that O-antigen variation serves to escape the immune response. Yes. Yet, even though highly variable, the O-side chain feature of LPS is conserved among most Gram-negatives, many that do not usually interact with animals with immune systems. For example, the cyanobacterial O-side chain is, overall, very similar to that of E. coli. It could be argued that long before there was immune evasion by human pathogens, O-side chain variability in cyanobacteria was already used to evade predation by protozoans. However, this is not likely to be have been the case. In at least one cyanobacterium, it seems the O-side chain actually helps attracts predators rather than help evade them because removal of the O-side chain by mutation leads to resistance from protozoan predation.
Most importantly, the overall conservation of a variable O-side chain among such distantly related bacteria points to a different selective pressure. Remember, bacteria had at least a billion years before there were any eukaryotes, not to mention protozoan predators or animals with immune systems! Given the deep conservation, it is reasonable to imagine that O-side chains were variable from very early on in Gram-negative evolution.
Can you think of any other bacterial predators that were around long before eukaryotes? Phages! Of course. The phage-bacteria ecology, their interactions, most likely served as the initial driver for O-side chain diversity. As phages reach into the cell envelope of a Gram-negative, they invariably must go through the O-side chain. Some phages have glycosidases that hydrolyze the O-side so a good defense strategy is for the bacterium to vary its saccharide composition. In fact, lysogenic phages themselves often encode glycosyl transferases that vary the structure of the O-side chain, providing immunity to superinfection by closely related phages.
I'm certainly not the first one to have thought of this possibility. In searching the literature, I found several excellent papers suggesting that phages serve as the selective driver for O-antigen diversity (for example, see here and here). Most likely phages were the first, by a long time. What do you think?
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