Kiss and Make Up: Myx­o­coc­cus xan­thus...

...demon­strates bac­te­r­ial co­op­er­a­tion

by Ada Ha­gan

If there's a hot topic in mi­cro­bi­ol­ogy, it's bac­te­r­ial in­ter­ac­tion and com­mu­ni­ca­tion. Bac­te­ria "talk" to each other us­ing a com­plex chem­i­cal lan­guage we are only just be­gin­ning to un­der­stand. Quo­rum sens­ing al­lows com­mu­ni­ca­tion be­tween spa­tially sep­a­rated cells of sim­i­lar species. Func­tion­ing sim­i­larly, bac­te­ri­ocins warn non-im­mune bac­te­ria away from a bacterium's es­tab­lished niche. Type VI se­cre­tion sys­tems also help a bac­terium pro­tect its niche, but by ini­ti­at­ing con­tact be­tween cells. Here, I'll de­scribe an­other in­stance of cell-to-cell in­ter­ac­tion where bac­te­ria don't just com­mu­ni­cate, but also heal.

Fig­ure 1. "Kiss and make up" with GFP ex­press­ing Esch­e­richia coli (A. Ha­gan)

First, a bit about the species in­volved. Myx­o­coc­cus xan­thus is con­sid­ered a "so­cial" species of bac­te­ria, re­quir­ing a large pop­u­la­tion to en­hance sur­viv­abil­ity. M. xan­thus ag­gre­gates move to­gether us­ing a form of twitch­ing-motil­ity to find nu­tri­ents, or if nu­tri­ents are lack­ing, to cre­ate a com­plex, dif­fer­en­ti­ated struc­ture. In it, some bac­te­ria make spores to en­sure long-term sur­vival against ex­treme con­di­tions.

Bac­te­r­ial cells must adapt in or­der to sur­vive changes in tem­per­a­tures, ra­di­a­tion ex­po­sure, or short­ages in food sup­ply. All of these stresses can slow a bacterium's abil­ity to repli­cate quickly or re­spond to dam­age in the DNA or outer mem­brane (OM).

Fig­ure 2. Two strains of M. xan­thus, ex­press­ing ei­ther a GFP-la­beled or mCherry-la­beled outer mem­brane pro­tein, were co-in­cu­bated on an agar sur­face for four hours. OME al­lowed cells to share the outer mem­brane pro­teins re­sult­ing in cells ac­quir­ing both la­bels, the ar­row in the merge panel points to one ex­am­ple. Source

Once dam­age oc­curs, most bac­te­ria are on their own to ei­ther re­pair and sur­vive, or die. Re­searchers at the Uni­ver­sity of Wyoming have re­cently learned M. xan­thus cells co­op­er­ate with each other to make re­pairs in the outer mem­brane (Fig­ure 2).

This process, called Outer Mem­brane Ex­change (OME), is a bidi­rec­tional trans­fer of the outer mem­brane lipopolysac­cha­ride (LPS) be­tween two bac­te­r­ial cells. Two sur­face pro­teins, TraA and TraB act some­what like Vel­cro hooks to bring cells close enough for OME to oc­cur, but are also re­spon­si­ble for OME speci­ficity. Un­like Vel­cro, which has rec­i­p­ro­cal hooks and latches, TraA pro­teins only rec­og­nize iden­ti­cal forms of TraA on the other bac­te­ria. In other words, if one bac­terium ex­presses TraA, and an­other TraA', they won't be able to per­form OME. This pre­vents M. xan­thus from ac­ci­den­tally help­ing dis­tantly re­lated, or ri­val, M. xan­thus pop­u­la­tions.

Once TraA and TraB have ini­ti­ated the junc­tion be­tween two bac­te­ria, they ap­pear to merge OM's, trad­ing LPS along with pro­teins at the cell sur­face (Fig­ure 3). This ef­fec­tively di­lutes the dam­age from a few bac­te­ria to the rest of the bac­te­r­ial pop­u­la­tion, thus en­hanc­ing sur­vival of the group.

Fig­ure 3. M. xan­thus ap­pear to merge outer membran­es dur­ing OME. Cryo-EM im­age. Source

In ad­di­tion to re­pair­ing dam­age to the outer mem­brane, the ex­change of LPS by OME helps re­store mo­bil­ity and the abil­ity to sporu­late. To demon­strate this, the au­thors cre­ated M. xan­thus mu­tants lack­ing wzm. The wzm genes are re­spon­si­ble for syn­the­sis of O‑antigen, which is re­quired for the for­ma­tion of fruit­ing bod­ies prior to sporu­la­tion and so­cial motil­ity. M. xan­thus lack­ing wzm are less motile and pro­duce fewer spores than the wzm con­tain­ing wild­type par­ent strain. If the mu­tant is grown with M. xan­thus ex­press­ing TraAB, how­ever, both motil­ity and sporu­la­tion im­prove. This is not the case when M. xan­thus Δwzm is co-cul­tured with M. xan­thus ΔtraA, since OME can­not oc­cur.

In an­other set of ex­per­i­ments, the au­thors looked at the ef­fect of OME on lpxC mu­tants. LpxC is re­quired for lipid A syn­the­sis, which is es­sen­tial for cell sur­vival. Us­ing a vanil­late in­ducible pro­moter, the cells ex­pressed LpxC and sur­vived. By with­hold­ing vanil­late, how­ever, re­searchers were able to de­plete LpxC from cells. OME from healthy donor cells ex­press­ing TraA was able to res­cue LpxC-de­pleted cells, en­abling sur­vival past 12 hours (Fig­ure 4).

Fig­ure 4. LpxC-de­pleted M. xan­thus (red), were not able to sur­vive with­out the pres­ence of TraA⁺ donors. De­tailed leg­end in Source

The ben­e­fits of OME don't stop there. OME helps im­prove cell per­me­abil­ity, and re­duces sen­si­tiv­ity to an­tibi­otics. It also acts as an in­for­ma­tion re­lay, im­prov­ing re­sponse to en­vi­ron­men­tal stres­sors. The au­thors sug­gest that in this sce­nario "scout cells" re­port on ex­te­rior en­vi­ron­men­tal con­di­tions via OME, shar­ing al­ter­ations in pro­tein ex­pres­sion or lipid mod­i­fi­ca­tions. This process would en­able the bac­te­r­ial pop­u­la­tion to adapt rapidly to their en­vi­ron­ment.

Fig­ure 5. Model of OME re­pair of a dam­aged popula­tion. In this model, a smaller dam­aged pop­u­la­tion is ab­sorbed into the larger healthy pop­u­la­tion and the dam­age di­luted by OME. The re­sult­ing ho­mo­ge­neous pop­u­la­tion has in­creased in size, cre­at­ing a more fit pop­u­la­tion for mul­ti­cel­lu­lar tasks. Source

There's also ev­i­dence sug­gest­ing that OME could be used for ne­far­i­ous pur­poses like elim­i­nat­ing cheat­ing mem­bers of the pop­u­la­tion. For in­stance, trans­fer of toxic pro­teins along with LPS could kill re­cip­i­ent bac­te­ria lack­ing im­mu­nity to the tox­ins.

Known to be "so­cial" bac­te­ria, Myx­o­coc­cus demon­strates be­hav­iors such as swarm­ing and com­plex biofilm for­ma­tion. OME, how­ever, re­quires more co­op­er­a­tion than pre­vi­ously ob­served, since oth­er­wise healthy bac­te­ria ac­cept dam­aged LPS. With ben­e­fits rang­ing from first aid to scout­ing out chang­ing en­vi­ron­ments, OME is truly a mul­ti­fac­eted sur­vival strat­egy. Does this give a new mean­ing to "kiss and make up?"

 

Ref­er­ence

Vas­sallo C, Pathak DT, Cao P, Zuck­er­man DM, Hoiczyk E, Wall D. (2015). Cell re­ju­ve­na­tion and so­cial be­hav­iors pro­moted by LPS ex­change in myxobac­te­ria. PNAS Plus, E2930−2946. DOI 10.1073/pnas.1503553112

 

Ada Ha­gan is a Ph.D. can­di­date in the Mi­cro­bi­ol­ogy and Im­munol­ogy De­part­ment, at the Uni­ver­sity of Michi­gan. She's a re­cip­i­ent of the ASM Robert D. Watkins Fel­low­ship and a co-found­ing ed­i­tor of the grad­u­ate stu­dent blog MiS­ci­Writ­ers. She's an as­pir­ing sci­ence com­mu­ni­ca­tor, fol­low her on Twit­ter (@adahagan) to see what else she'll come up with!