High­lights of 2010

by Elio and Mark O. Mar­tin

We asked friends and col­leagues to point to pa­pers pub­lished in 2010 that tick­led their fancy. Here are their re­sponses.

Michael Yarmolin­sky

Click here to view an an­i­ma­tion of the ac­tion of ParC and ParM in plas­mid R100 seg­re­ga­tion. Source

An ar­ti­cle pub­lished in 2010 that strikes me as par­tic­u­larly note­wor­thy is ATP con­trol of dy­namic P1 ParA-DNA in­ter­ac­tions: a key role for the nu­cleoid in plas­mid par­ti­tion by Vec­chiarelli, Han,Tan, M Mizu­uchi, Ghirlando, Biertümpfel, Fun­nell, and Mizu­uchi.

The or­derly seg­re­ga­tion (par­ti­tion) of plas­mids and many bac­te­r­ial chro­mo­somes is achieved with the aid of a par operon of two struc­tural genes and a site on the DNA to which one of the two Par pro­teins binds. The other Par pro­tein, in­volved in au­toreg­u­la­tion of the operon, is an AT­Pase of ei­ther the Walker type or actin-like. De­spite the sim­plic­ity of these sys­tems, their mech­a­nisms of ac­tion have long re­mained ob­scure. Par­ti­tion in­volv­ing an actin-like AT­Pase was fi­nally elu­ci­dated in a strik­ing pa­per pub­lished in 2007 by Gar­ner, Camp­bell, Weibel, and Mullins. Only in 2010 was a co­gent ex­pla­na­tion of­fered for the mech­a­nism of genome par­ti­tion me­di­ated by the Par sys­tem with an AT­Pase of the Walker type.

The cited pa­per is not easy read­ing. Were the mech­a­nism sim­ple, it would have been dis­cov­ered long ago. The model makes use of a re­ac­tion-dif­fu­sion mech­a­nism of pat­tern for­ma­tion and a care­ful analy­sis of spa­tial and ki­netic pa­ra­me­ters. I be­lieve that this kind of analy­sis will be re­quired to elu­ci­date the mys­ter­ies of de­vel­op­ment. This work is a re­minder of biology's debt to Alan Tur­ing, who un­der­stood that dif­fu­sion can play a de­ci­sive role in form­ing as well as in dis­rupt­ing patterns.A re­lated pa­per by Hatano and Niki was re­cently pub­lished in the same jour­nal.

Charles Yanof­sky

Al­though many of the pa­pers I have read re­cently are ex­cel­lent, they don't stand out as much as the two ar­ti­cles in the lat­est is­sue of Mi­crobe on Charles Darwin's con­tri­bu­tions, one by Kolter and Maloy and the other by Lenski.

David Lip­son

Pro­posed model for tax­o­nom­i­cally and meta­bol­i­cally sta­ble ecosys­tems. Solid lines = mi­crobes; dashed lines = viruses. (a) Mi­cro­bial taxa and their co-oc­cur­ring phage taxa co­ex­ist sta­bly over time. (b) Three mi­cro­bial taxa (Black, Blue, and Green spp.) and their phages are di­a­grammed sep­a­rately. Un­der­ly­ing the rel­a­tively sta­ble species pop­u­la­tions is a dy­namic cy­cling of mi­cro­bial strains and vi­ral geno­types. This cy­cling of preda­tor and prey pop­u­la­tions is con­sis­tent with a Kill-the-Win­ner dy­namic op­er­at­ing at the level of virus-sen­si­tive mi­crobial strains. Source

Love it or hate it (well, most mi­cro­bi­ol­o­gists seemed to hate it), the Wolfe-Si­mon et al. 2010 pa­per about the crazy ar­senic bug de­serves some kind of recog­ni­tion. It's rare to see en­vi­ron­men­tal mi­cro­bi­ol­ogy make that big of a splash in the gen­eral press. Too bad they didn't treat their DNA with pro­tease be­fore an­a­lyz­ing the ar­senic con­tent. Hope­fully it won't turn out to be a bust (Christoph added in 2026: it turned out to be a bust: GFAJ‑1 is a run-of-the-mill Oceanospir­il­lales bug, no 'alien life form'. The Wolfe-Si­mon et al. pa­per hasn't been re­tracted though).

The Mono Lake "ar­senic bug" GFAJ‑1 grown on ar­se­n­ate. Source

(When chal­lenged about this choice, David had this to say: What I love about mi­crobes is that they will ex­ploit the slimmest niche that na­ture of­fers them. Pro­vide a ther­mo­dy­nam­i­cally-fa­vor­able op­tion for mak­ing a liv­ing, no mat­ter how crappy, and some bug will evolve to use it. I love the pos­si­bil­ity that life in the uni­verse could take what­ever form the lo­cal chem­istry de­mands, and could be noth­ing like life as we know it.)

For­est Ro­hwer

Vi­ral and mi­cro­bial com­mu­nity dy­nam­ics in four aquatic en­vi­ron­ments is the best pa­per of 2010...but no one un­der­stands it. 🙂

Nanne Nan­ninga

Av­er­age rates of gene birth (red), du­pli­ca­tion (blue), HGT (green), and loss (yel­low) per lin­eage (events per 10 Myr per lin­eage) are shown. Events that in­crease gene count are plot­ted to the right, and gene loss events are shown to the left. The in­set shows meta­bolites or classes of meta­bolites or­dered ac­cord­ing to the num­ber of gene fam­i­lies that use them that were born dur­ing the Ar­chaean Ex­pan­sion com­pared with the num­ber born be­fore the ex­pan­sion, plot­ted on a log2 scale. Bars are coloured by func­tional an­no­ta­tion or com­pound. Source

Cre­ation of a bac­te­r­ial cell con­trolled by a chem­i­cally syn­the­sized genome by Gib­son and co-work­ers from the Ven­ter labs is cer­tainly "par­tic­u­larly in­ter­est­ing." What I like apart from the method­olog­i­cal achieve­ment is the term "cre­ation" in the ti­tle. What I did not like was the fuss in the press for the wrong rea­sons.

An­other pa­per which I be­lieve mer­its at­ten­tion is en­ti­tled Rapid evo­lu­tion­ary in­no­va­tion dur­ing an Ar­chaean ge­netic ex­pan­sion by Lawrence A. David and Eric J. Alm in Na­ture (Pub­lished on line 19 De­cem­ber 2010).The au­thors traced the his­tory of about 4,000 gene fam­i­lies in deep time. In their method they in­cor­po­rated the phe­nom­e­non of hor­i­zon­tal gene trans­fer (HGT). They have in­ter­preted their data to mean that rates of gene birth, gene du­pli­ca­tion, gene loss and HGT vary over ge­o­log­i­cal timescales. They pos­tu­lated an in­creased gene fam­ily birth roughly about 3,000 bil­lion years ago and which they termed Ar­chaean Ex­pan­sion. New genes seem to be in­volved in elec­tron-trans­port and res­pi­ra­tory path­ways. As pointed out by the au­thors this pre­cedes the in­crease in oxy­gen in the at­mos­phere. I feel this work com­ple­ments stud­ies in­volv­ing bio­fos­sils and chemo­fos­sils.

Michel Malamy

Among many very in­ter­est­ing pa­pers ap­pear­ing in 2010, I want to es­pe­cially men­tion the pa­per of Wang, Robert, Pel­letier, Dang, Tad­del, Wright, and Jun en­ti­tled Ro­bust Growth of E.coli. The au­thors em­ployed a mi­croflu­idic de­vice that en­abled them to fol­low the growth and di­vi­sion of sin­gle bac­te­r­ial cells over a long pe­riod of time. The re­sults are sur­pris­ing and serve as a nice fol­low up to the work of the "Maaløe school."

Con­rad Woldringh

Click here to view a movie of the first 100 min­utes of a rep­re­sen­ta­tive time lapse ex­per­i­ment show­ing 12 fields. Source

For me the most in­ter­est­ing ar­ti­cle in 2010 is that of Jun and Wright en­ti­tled En­tropy as the dri­ver of chro­mo­some seg­re­ga­tion. The au­thors try to give a phys­i­cal an­swer to the ques­tion of bac­te­r­ial seg­re­ga­tion based on the phe­nom­e­non of en­tropic de-mix­ing of newly repli­cated DNA daugh­ter strands. This sub­ject refers to a pre­vi­ously dis­cussed topic that was started with the ques­tion: Bac­te­r­ial Mi­to­sis: What's Tak­ing So Long? (The for­mu­la­tion of this ques­tion is based on eu­kary­otic ter­mi­nol­ogy. See the com­ments on this topic of July, 2007.)

The im­por­tance of the present pa­per is the pre­dic­tion that, while plas­mids need cy­toskele­tal el­e­ments for their seg­re­ga­tion, such ma­chin­ery is nei­ther needed for chro­mo­so­mal seg­re­ga­tion in bac­te­ria nor for chro­matid sep­a­ra­tion in eu­kary­otes.

Al­though en­tropy is a force­ful dri­ving force it has no di­rec­tion­al­ity and thus can­not it­self bring about seg­re­ga­tion. Ad­di­tional bi­o­log­i­cal con­di­tions have to guide this force. The au­thors there­fore pro­pose the ex­is­tence of a con­cen­tric shell around the nu­cleoid to where the repli­somes and the newly repli­cated "strings of DNA blobs" are ex­truded. It is in this outer shell that the daugh­ter strands demix and re­pel each other by chain-con­nec­tiv­ity and vol­ume-ex­clu­sion in­ter­ac­tions, with the ad­di­tional help of DNA bind­ing pro­teins and pos­si­bly the transer­tion process.

Click here to view a sim­u­la­tion of en­tropy dri­ven de­mixing of newly repli­cated DNA daugh­ter strands. Source

We do not know whether such a shell ex­ists. More­over, ini­ti­a­tion of DNA repli­ca­tion may have to oc­cur some­where within the nu­cleoid and out­ward ex­tru­sion of the ori­some may be a too slow process. We thus must think of an even sim­pler mech­a­nism that can oc­cur and func­tion in­side the nu­cleoid. Prob­a­bly, the mech­a­nism should also func­tion un­der con­di­tions of tran­scrip­tion and growth in­hi­bi­tion. Un­pub­lished ob­ser­va­tions (with Flem­ming Hansen) have in­di­cated that dur­ing run-off DNA syn­the­sis, re­gions on the two chro­mo­some arms not only du­pli­cate but also fully seg­re­gate to both halves of the nu­cleoid.

As the au­thors sug­gest, mea­sure­ments of the dy­nam­ics of la­beled DNA re­gions us­ing flu­o­res­cence cor­re­la­tion spec­troscopy (FCS) and pos­si­bly also im­age cor­re­la­tion spec­troscopy (ISC) can still be im­proved and ap­plied on both liv­ing cells and iso­lated nu­cleoids. I am quite con­fi­dent, there­fore, that it is not "Tak­ing So Long" any­more be­fore we can an­swer some cru­cial ques­tions about "bac­te­r­ial mi­to­sis."

Mar­garet Mc­Fall-Ngai

I'd vote for the pa­per on Drosophila mi­crobes af­fect­ing the fly's mat­ing be­hav­ior. The story from Eu­gene Rosenberg's lab came out in PNAS at the end of 2010.
(In fact, Merry wrote about it on STC.)

Lisa Gorski

De­tail of the Black Cow Panel in the Main Gallery. Source

I'm fas­ci­nated by the idea that by open­ing up these trea­sures (in this case the pre­his­toric draw­ings in the Las­caux caves) so that we can see and study them, you al­ter the en­vi­ron­ment such that the new mi­crobes that grow can de­stroy the thing you want to study. Kind of hits my two pas­sions in want­ing to know about mi­cro­bi­ol­ogy and want­ing to study an­cient civ­i­liza­tions.

I also find it in­ter­est­ing that in just the few decades that the caves have been open to the pub­lic hu­man pathogens have be­come part of the flora found in the caves. I found this ar­ti­cle  on the mi­cro­bi­ol­ogy of the Las­caux caves by French, Span­ish, and Czech mi­cro­bi­ol­o­gists to be quite in­ter­est­ing.

Yuri Gorby

From my per­spec­tive and in­ter­ests, the most ex­cit­ing pa­per I read this year came from the Danes Lars Pe­ter Nielsen and Nils Ris­gaard-Pe­tersen. (We just dis­cussed this one in class.) The next was from Zara Sum­mers and col­leagues, pub­lished in Sci­ence a cou­ple of months ago, show­ing in­ter­species elec­tron trans­fer.

Mark Mar­tin

I have be­come in­creas­ingly in­ter­ested in the in­ter­ac­tions be­tween mi­crobes and other organisms—a bud­ding (!) so­ciomi­cro­bi­ol­o­gist, per­haps. We are walk­ing ecolo­gies, in a man­ner of speak­ing, and in­ter­ac­tions be­tween mem­bers of those ecolo­gies is the rule. I have two choices of thought pro­vok­ing ar­ti­cles pub­lished in 2010.

Win­ter, SE, et al. (2010). Gut in­flam­ma­tion pro­vides a res­pi­ra­tory elec­tron ac­cep­tor for Sal­mo­nella. Na­ture 467: 426–429.

In this re­mark­able ar­ti­cle, it was dis­cov­ered that Sal­mo­nella uses its path­o­genic as­so­ci­a­tion with host cells dur­ing in­fec­tion to give it­self a growth ad­van­tage: in­flam­ma­tion of ep­ithe­lial cells due to T3SS pro­duces re­ac­tive oxy­gen species, which in turn cre­ate a res­pi­ra­tory elec­tron ac­cep­tor (tetrathion­ate) that Sal­mo­nella can use to com­pete with non­path­o­genic gut mi­crobes. A re­mark­able mi­cro­bial de­tec­tive tale, be­gin­ning with ob­ser­va­tions in the 1920s!

Fierer, N. et al. (2010). Foren­sic iden­ti­fi­ca­tion us­ing skin bac­te­r­ial com­mu­ni­ties. Proc. Natl. Acad. Sci. 107: 6477–6481.

We not only main­tain com­plex com­mu­ni­ties of mi­crobes on our skin, but those com­mu­ni­ties re­flect our in­di­vid­u­al­i­ties. In a "CSI" meets "Ar­row­smith" mo­ment, the au­thors demon­strate that the skin mi­cro­biota can be as in­di­vid­ual as a fin­ger­print, and those "mi­cro­bial fin­ger­prints" are left when­ever we touch a sur­face.

Merry

Frames from a time-lapse movie de­pict­ing in­fec­tion events. At t = 0 (left), two cells are seen each in­fected by a sin­gle phage (green spots), and one cell is in­fected by three phages. At t = 80 min (mid­dle), the two cells in­fected by sin­gle phages have each gone into the lytic path­way, as in­di­cated by the in­tra­cel­lu­lar pro­duc­tion of new phages (green). The cell in­fected by three phages has gone into the lyso­genic path­way, as in­di­cated by the pro­duc­tion of mCherry from the P_RE pro­moter (red). At t = 2 hr (right), the lytic path­way has re­sulted in cell ly­sis, whereas the lyso­genic cell has di­vided. Source

I'd men­tion two pa­pers that re­vis­ited pre­vi­ously known processes, but now look­ing at the sin­gle cell or sin­gle phage level. The first one, by Ken­zaka and col­leagues, was the ba­sis of my blog post, Promis­cu­ous Bac­te­ria and Play­boy Viruses. Sig­nif­i­cantly, they found that phage can trans­fer genes to non-hosts, i.e., to bac­te­ria that they can't suc­cess­fully in­fect. This makes sense in that many host de­fenses, such as CRISPRs and re­stric­tion-mod­i­fi­ca­tion sys­tems, do not block in­jec­tion of phage DNA, but in­stead abort the in­fec­tion at a later step. That way the bac­terium nets some new genes and/or a free nu­cleotide lunch.

T Ken­zaka, K Tani, and M Nasu. High-fre­quency phage-me­di­ated gene trans­fer in fresh­wa­ter en­vi­ron­ments de­ter­mined at sin­gle-cell level. The ISME Jour­nal (2010) 4: 648–659.

In my sec­ond se­lec­tion, Zeng et al. dis­sect the process by which, upon en­ter­ing a host, in­di­vid­ual λ phages choose ly­sis or lysogeny. Their choice is gov­erned by the con­cen­tra­tion of phage genomes within the cell, thus is in­flu­enced by the mul­ti­plic­ity of in­fec­tion and the phys­i­o­log­i­cal state of the host (read that as "cell size"). They then show that a un­aminous vote is re­quired by all phages in the cell in or­der to en­ter the lysogeny path­way.

L Zeng et al. De­ci­sion Mak­ing at a Sub­cel­lu­lar Level De­ter­mines the Out­come of Bac­te­rio­phage In­fec­tion. Cell (2010) 141: 682–691.

Elio was spot on when he said we had ar­rived in a new Age of Imag­ing.