Mi­cro­bial So­ci­ol­ogy

by Elio

Few top­ics of re­cent have been as tit­il­lat­ing as communi­cation among bac­te­ria. Just like in­sects, bac­te­ria "talk" to each other in a chem­i­cal lan­guage, ask­ing one an­other ques­tions such as: How many of us are there? Is it time to make a biofilm? Do con­di­tions call for mak­ing tox­ins? and (the grand­fa­ther of them all) Should we turn on the light? Most of the time, the con­ver­sa­tion doesn't get started un­til the pop­u­la­tion den­sity has reached a thresh­old level – why de­bate the is­sue if you don't have a quo­rum? Thus, "quo­rum sens­ing" is the apt term used for this lin­guis­tic skill.

Beauty can be com­plex: 'Im­pro­vi­sa­tion 31' by Wass­ily Kandin­sky (1913). Source

Typ­i­cally, the mes­sages com­mu­ni­cated im­pact the in­di­vid­ual first, and only later the group. Ul­ti­mately, a species may well gain from, say, the timely mak­ing of a biofilm, but each cell that plays this game may get an im­me­di­ate re­ward. There are in­stances when the mes­sage is less be­nign. E. coli cells, it turns out, some­times also tell each other when it's time for some of them to com­mit sui­cide. One in­ter­pre­ta­tion is that this hap­pens in times of nu­tri­tional or other stresses; the dy­ing bac­te­ria lyse, re­leas­ing nu­tri­ents that can ben­e­fit their com­pa­tri­ots.

Much is known about one mech­a­nism that leads to this be­hav­ior, termed bac­te­r­ial pro­grammed cell death. Two E. coli pro­teins, MazE and MazF, are in­volved. MazF is a sta­ble toxin, MazE a la­bile an­ti­dote. Stop pro­tein syn­the­sis in any of a num­ber of ways and the MazE level will drop, giv­ing the sta­ble MazF free rein to kill the cell. When the genes for the toxin and an­ti­dote are en­coded on a plas­mid, the arrange­ment is known as an ad­dic­tion mod­ule. Lose your plas­mid, and you're dead. It has been dis­cussed that toxin-an­ti­toxin sys­tems may have sev­eral hy­po­thet­i­cal func­tions.

The apop­to­sis path­way. In eu­kary­otes, pro­grammed cell death is quite in­tri­cate. Will it turn out to be sim­pler in bac­te­ria? Credit: Merck

For some time, it has been known that a sol­u­ble extra­cellular fac­tor is in­volved and that it is made in re­sponse to quo­rum sens­ing. The ex­cit­ing re­cent news is that this fac­tor has been iden­ti­fied as the some­what un­usual lin­ear pen­tapep­tide, NNWNN (as­paragine – as­paragine – tryp­to­phan – as­paragine – as­paragine). Iden­ti­fi­ca­tion of the com­pound was no small task. It re­quired de­fy­ing the ex­perts by mod­i­fy­ing the stan­dard mass spec­trom­e­try pro­to­col to elim­i­nate the acid pH to which this pep­tide is sen­si­tive. Given the right con­di­tions, the NNWNN pep­tide is a po­tent killer in nanogram amounts. Its ac­tion is re­lated to the MazE/MazF story since dele­tions in those genes ren­der the cells in­sen­si­tive to the pep­tide. The mech­a­nism of the peptide's ac­tion awaits elu­ci­da­tion.

Mean­while, there is more ex­cite­ment: the source of the NNWNN pep­tide ap­pears not to be a de­­dicated syn­thetic sys­tem, but rather it is clipped from the en­zyme glu­cose-6-phos­phate dehydro­genase. What might such a meta­bolic en­zyme have to do with these higher or­der phe­nom­ena? As noted in a Per­spec­tive in Sci­ence:

"...it seems rea­son­able that it [the pep­tide] is made when the bac­terium, for rea­sons un­known, be­gins to de­stroy this en­zyme. Thus, an ap­par­ent in­ter­nal stress, such as the on­set of star­va­tion, could gen­er­ate this sig­nal, which is se­creted (per­haps by some mori­bund cells in the pop­u­la­tion) and primes the pop­u­la­tion such that some cells can be killed through the pro­grammed cell death path­way when con­fronted with other stresses."

Other toxin/antitoxin sys­tems ex­ist in E. coli, and elu­ci­dat­ing their roles and pos­si­ble in­ter­ac­tions will add to the fas­ci­na­tion of this story. As it stands, this work al­ready rep­re­sents a very ex­cit­ing chap­ter in the un­fold­ing field of Mi­cro­bial So­ci­ol­ogy.

Think­ing about these find­ings eco­log­i­cally, we pon­der where E. coli might be liv­ing for this pheno­menon to take place. The site must have enough E. coli cells liv­ing in close prox­im­ity to ac­ti­vate quo­rum sens­ing. The mam­malian in­tes­tine may not qual­ify. E. coli is found in small  num­bers in the lu­men of the ter­mi­nal ileum of healthy peo­ple and they may well be stressed there, al­though prob­a­bly not for lack of nu­tri­ents. Is this pop­u­la­tion large enough for quo­rum sens­ing? Who knows! Go­ing on down the GI tract, the colon seems an even less likely venue, given that E coli are mi­nor­ity in­hab­i­tants sur­rounded there by about a thou­sand anaer­obes each. How about in bod­ies of wa­ter? Here, E. coli sug­gests fe­cal con­t­a­m­i­na­tion be­cause it is said to sur­vive poorly in such en­vi­ron­ments and thus to be present only tran­siently (an ar­guable point). But the num­bers are low here too. San­i­tary en­gi­neers close beaches when the "co­l­iform" count reaches a hand­ful of cells per ml. What other pos­si­bil­i­ties does this leave us? Per­haps sites where E. coli acts as a pathogen. In the blad­der, uropath­o­genic strains make biofilms; like­wise for some en­terovir­u­lent ones. Given the va­ri­ety of dis­eases caused by this or­gan­ism, the choices are many.

We don't know enough at present about the ecol­ogy of E. coli to say much more. The ques­tion seems open and ready for cre­ative ex­per­i­ments. We ex­pect that such stud­ies are or will soon be un­der­way. For now, this phe­nom­e­non joins the long list of those that can­not eas­ily be re­lated to the organism's ecol­ogy. Fair to say, this is pretty much the rule: a huge num­ber of phys­i­o­log­i­cal phe­nom­ena are wait­ing for a habi­tat. Such con­cerns, how­ever, do not de­tract from the ex­cite­ment of this par­tic­u­lar work. In fact, it promises a bright fu­ture for the field of bac­te­r­ial com­mu­ni­ca­tion.