Bacteria are the oldest living organisms on the earth. They've been here for billions of years, and what they are are single-celled microscopic organisms. So they're one cell and they have this special property that they only have one piece of DNA. So they have very few genes and genetic information to encode all of the traits that they carry out. And the way bacteria make a living is that they consume nutrients from the environment, they grow to twice their size, they cut themselves down in the middle, and one cell becomes two, and so on and so on. They just grow and divide and grow and divide -- so a kind of boring life, except that what I would argue is that you have an amazing interaction with these critters.
Bakterije su najstariji živući organizmi na Zemlji. Ovdje su milijardama godina. i u stvari oni su jednostanični mikroskopski organizmi. Dakle, oni su u stvari jedna stanica i imaju posebno svojstvo da imaju samo jedan komad DNA. Imaju vrlo malo gena, i gensku informaciju kako bi kodirali sva svojstva koja izvršavaju. A način na koji bakterije preživljavaju je taj da crpe hranjive tvari iz okoliša, narastu do dvostruke svoje veličine, presijeku se napola po sredini, i od jedne stanice nastanu dvije, i tako dalje, i tako dalje. One samo rastu i dijele se, rastu i dijele se -- dakle, poprilično dosadan život, no pored toga bih vam željela dokazati, da vi imate čudesnu interakciju s ovim stvorenjima.
I know you guys think of yourself as humans, and this is sort of how I think of you. This man is supposed to represent a generic human being, and all of the circles in that man are all the cells that make up your body. There's about a trillion human cells that make each one of us who we are and able to do all the things that we do. But you have 10 trillion bacterial cells in you or on you at any moment in your life. So, 10 times more bacterial cells than human cells on a human being. And, of course, it's the DNA that counts, so here's all the A, T, Gs and Cs that make up your genetic code and give you all your charming characteristics. You have about 30,000 genes. Well, it turns out you have 100 times more bacterial genes playing a role in you or on you all of your life. So at the best, you're 10 percent human; more likely, about one percent human, depending on which of these metrics you like. I know you think of yourself as human beings, but I think of you as 90 or 99 percent bacterial.
Znam da o sebi mislite kao o ljudskim bićima, a ovo je otprilike što ja mislim o vama. Ovaj čovjek bi trebao predstavljati općenito ljudsko biće, i svi krugovi u ovom čovjeku predstavljaju sve stanice koje tvore vaše tijelo. Postoji oko trilijun ljudskih stanica od kojih se sastoji svatko od nas tko smo i što smo sve u stanju činiti, međutim, vi posjedujete 10 trilijuna bakterijskih stanica u vama i na vama u svakom trenutku vašega života. Znači, 10 puta više bakterijskih stanica nego ljudskih stanica po ljudskom biću. I naravno, DNA su te koje se broje, dakle, ovdje su svi A, T, G-ovi i C-ovi koji sačinjavaju vaš genetički kod, i daju vam sve vaše dražesne osobine. Imate oko 30.000 gena. Po tome ispada da imate 100 puta više bakterijskih gena koje imaju neku ulogu u ili na vama tijekom cijelog vašeg života. U najboljem slučaju, vi ste 10 posto čovjek, no vjerojatnije je da ste jedan posto čovjek, ovisno o tome koja vam se metrika više sviđa. Znam da o sebi mislite kao o ljudskim bićima, no, ja o vama mislim kao o 90 ili 99 postotnim bakterijama.
(Laughter)
(Smijeh)
And these bacteria are not passive riders. These are incredibly important; they keep us alive. They cover us in an invisible body armor that keeps environmental insults out so that we stay healthy. They digest our food, they make our vitamins, they actually educate your immune system to keep bad microbes out. So they do all these amazing things that help us and are vital for keeping us alive, and they never get any press for that. But they get a lot of press because they do a lot of terrible things as well. So there's all kinds of bacteria on the earth that have no business being in you or on you at any time, and if they are, they make you incredibly sick.
Ove bakterije nisu pasivni putnici, i one su nevjerojatno važne, one nas održavaju živima. Prekrivaju nas nevidljivim oklopom koji nas štiti od vanjskih ozljeda te tako ostajemo zdravi. Oni probavljaju našu hranu, oni tvore naše vitamine, oni u stvari podučavaju naš imunosni sustav kako ne dozvoliti lošim mikrobima pristup. Znači, oni čine sve te čudesne stvari koje nam pomažu i koje su neophodne kako bismo bili živi, i zbog toga nikad nisu u bilo kakvoj stisci. Međutim, mnogo se piše o njima, jer čine mnoge užasne stvari. Prema tome, postoje mnoge vrste bakterija na Zemlji koje ne bi trebale biti u ili na vama nikada, a ako jesu, čine vas nevjerojatno bolesnim.
And so the question for my lab is whether you want to think about all the good things that bacteria do or all the bad things that bacteria do. The question we had is: How could they do anything at all? I mean, they're incredibly small. You have to have a microscope to see one. They live this sort of boring life where they grow and divide, and they've always been considered to be these asocial, reclusive organisms. And so it seemed to us that they're just too small to have an impact on the environment if they simply act as individuals. So we wanted to think if there couldn't be a different way that bacteria live.
I tako, pitanje za moj laboratorij je želite li misliti samo o dobrim stvarima koje bakterije čine, ili samo o lošim koje one čine. Pitanje koje se nameće je kako one uopće mogu bilo što raditi? Mislim, one su nevjerojatno malene, neophodan vam je mikroskop kako biste jednu od njih vidjeli. Žive taj dosadan život u kojem samo rastu i dijele se, i uvijek ih se smatralo za nedruštvene, samotnjačke organizme. Tako, izgledalo nam je da su isuviše mali a da bi imali utjecaj na okolinu ako jednostavno djeluju kao jedinke. I željeli smo razmisliti ne bi li mogao postojati drugačiji način kako bakterije žive.
And the clue to this came from another marine bacterium, and it's a bacterium called "Vibrio fischeri." What you're looking at on this slide is just a person from my lab holding a flask of a liquid culture of a bacterium, a harmless, beautiful bacterium that comes from the ocean, named Vibrio fischeri. And this bacterium has the special property that it makes light, so it makes bioluminescence, like fireflies make light. We're not doing anything to the cells here, we just took the picture by turning the lights off in the room, and this is what we see.
Ključ rješenja za ovo nam je pružila jedna druga morska bakterija, a ona se zove Vibrio fischeri. Ono što vidite na ovom dijapozitivu je jedna osoba iz moga laboratorija kako drži tikvicu sa tekućom kulturom bakterija, bezopasnih i prelijepih bakterija koje potječu iz oceana, imena Vibrio fischeri. Ove bakterije imaju naročito svojstvo da stvaraju svijetlost, i tako stvaraju bioluminiscenciju, isto kao što krijesnice stvaraju svijetlost. Ovdje nismo ništa radili sa stanicama. Samo smo snimili fotografiju prethodno ugasivši svjetlost u prostoriji, i evo što se vidi.
And what's actually interesting to us was not that the bacteria made light but when the bacteria made light. What we noticed is when the bacteria were alone, so when they were in dilute suspension, they made no light. But when they grew to a certain cell number, all the bacteria turned on light simultaneously. So the question that we had is: How can bacteria, these primitive organisms, tell the difference from times when they're alone and times when they're in a community, and then all do something together? And what we figured out is that the way they do that is they talk to each other, and they talk with a chemical language.
Ono što nam je zapravo bilo zanimljivo nije bilo to što bakterije svijetle, nego kada one to čine. Zamijetili smo da kada su bakterije bile same, znači kad su u bile u razrijeđenom rastvoru, nisu stvarale svjetlost. Međutim, kad su narasle do određenog broja stanica sve bakterije su upalile svjetla istovremeno. Pitanje koje se nametnulo je kako mogu bakterije, ti primitivni organizmi, razlikovati vrijeme kad su same, od vremena kad su u nekoj zajednici, i zatim sve odreda učiniti nešto zajedno. Ono što smo zaključili je da je način kako to one čine putem međusobnog razgovora, a razgovaraju jezikom kemije. Ovo bi trebala biti stanica bakterije.
So this is now supposed to be my bacterial cell. When it's alone, it doesn't make any light. But what it does do is to make and secrete small molecules that you can think of like hormones, and these are the red triangles. And when the bacteria are alone, the molecules just float away, and so, no light. But when the bacteria grow and double and they're all participating in making these molecules, the molecule, the extracellular amount of that molecule, increases in proportion to cell number. And when the molecule hits a certain amount that tells the bacteria how many neighbors there are, they recognize that molecule and all of the bacteria turn on light in synchrony. And so that's how bioluminescence works -- they're talking with these chemical words.
Kada je sama ona ne stvara svjetlost. No, ono što čini je da stvara i izlučuje malene molekule koje možete zamisliti kao hormone, a to su ovi crveni trokutovi, i kada je bakterija sama molekule jednostavno odplutaju i onda nema svjetlosti. Međutim, kada bakterija naraste i umnoži se i kada sve one sudjeluju u stvaranju ovih molekula, molekula -- izvanstanična količina te molekule se povećava proporcionalno broju stanica. A onda kada molekule dosegnu određeni broj to govori bakteriji koliko susjeda ima, one prepoznaju tu molekulu i sve bakterije sinkronizirano upale svjelost. Tako funkcionira bioluminiscencija -- one ragovaraju pomoću kemijskih riječi.
The reason Vibrio fischeri is doing that comes from the biology -- again, another plug for the animals in the ocean. Vibrio fischeri lives in this squid. What you're looking at is the Hawaiian bobtail squid. It's been turned on its back, and what I hope you can see are these two glowing lobes. These house the Vibrio fischeri cells. They live in there, at high cell number. That molecule is there, and they're making light. And the reason the squid is willing to put up with these shenanigans is because it wants that light.
Razlog zašto Vibrio fischeri to čine potječe iz biologije. I opet, još jedna utičnica za životinje u oceanu, Vibrio fischeri živi u ovoj lignji. Ono što gledate je Havajska kratkorepa lignja, i izokrenuta je na leđa, i ono što se nadam da vidite jesu ova dva krilca koja svijetle a koja nastanjuju stanice Vibrio fischeri, one žive tamo, kada je broj stanica velik ta molekula je tamo, i one stvaraju svjetlost. Razlog zašto je lignja voljna podnositi ovakve smicalice je što želi svjetlost.
The way that this symbiosis works is that this little squid lives just off the coast of Hawaii, just in sort of shallow knee-deep water. And the squid is nocturnal, so during the day, it buries itself in the sand and sleeps. But then at night, it has to come out to hunt. So on bright nights when there's lots of starlight or moonlight, that light can penetrate the depth of the water the squid lives in, since it's just in those couple feet of water. What the squid has developed is a shutter that can open and close over the specialized light organ housing the bacteria. And then it has detectors on its back so it can sense how much starlight or moonlight is hitting its back. And it opens and closes the shutter so the amount of light coming out of the bottom, which is made by the bacterium, exactly matches how much light hits the squid's back, so the squid doesn't make a shadow. So it actually uses the light from the bacteria to counter-illuminate itself in an antipredation device, so predators can't see its shadow, calculate its trajectory and eat it. So this is like the stealth bomber of the ocean.
Ovakva simbioza funkcionira jer ova mala lignja živi uza samu obalu Havaja, baš u plitkoj vodi koja doseže do koljena. Lignja je noćna životinja, te je preko dana zakopana u pijesak i spava, a onda noću mora izaći van da bi lovila. Za vrijeme vedrih noći kada ima dosta svjetlosti zvijezda ili je mjesečina ta svjetlost može prodrijeti kroz dubinu vode u kojoj lignja živi, zato što je to samo nekoliko stopa vode. Ono što je lignja razvila je neka vrsta preklopnika kojega otvara i zatvara iznad tog specijaliziranog svjetlosnog organa s bakterijama. Zatim ima detektore na leđima tako da može osjetiti koliko mjesečine ili svjetlosti zvijezda pada na njena leđa. Onda ona otvara ili zatvara preklopnik tako da količina svjetlosti koja dolazi sa dna -- a koju stvaraju bakterije -- točno odgovara količini svjetlosti koja udara o leđa lignje, na taj način lignja ne stvara sjenu. U stvari ona koristi svjetlost bakterija za kontra-osvjetljenje sebe, kao uređaj za zaštitu od predatora tako, grabežljivci ne mogu vidjeti njenu sjenu, procijeniti njenu putanju i pojesti je. Ovo nalikuje na oceanske nevidljive bombardere.
(Laughter)
(Smijeh)
But then if you think about it, this squid has this terrible problem, because it's got this dying, thick culture of bacteria, and it can't sustain that. And so what happens is, every morning when the sun comes up, the squid goes back to sleep, it buries itself in the sand, and it's got a pump that's attached to its circadian rhythm. And when the sun comes up, it pumps out, like, 95 percent of the bacteria. So now the bacteria are dilute, that little hormone molecule is gone, so they're not making light. But, of course, the squid doesn't care, it's asleep in the sand. And as the day goes by, the bacteria double, they release the molecule, and then light comes on at night, exactly when the squid wants it.
Onda kad bolje razmislite o ovome, lignja ima ovaj strašan problem zato što ima ovu umiruću, zgusnutu kulturu bakterija i ne može ih održavati. I onda što se dešava, svako jutro kada sunce izlazi lignja odlazi na spavanje, ukopavavajući se u pijesak, ona ima pumpu koja je uklopljena u njen svakodnevni ritam, i kada sunce izađe ona ispumpava nekih 95 posto bakterija. Sada su bakterije razrijeđene, ona mala hormonska molekula je nestala, tako da one ne stvaraju svjetlost -- no naravno lignja za to ne mari. Ona spava u pijesku. I kako dan odmiče bakterije se množe, oslobađaju molekulu, i svjetlost nastaje noću, točno onda kada lignji treba.
So first, we figured out how this bacterium does this, but then we brought the tools of molecular biology to this to figure out, really, what's the mechanism. And what we found -- so this is now supposed to be my bacterial cell -- is that Vibrio fischeri has a protein. That's the red box -- it's an enzyme that makes that little hormone molecule, the red triangle. And then as the cells grow, they're all releasing that molecule into the environment, so there's lots of molecule there. And the bacteria also have a receptor on their cell surface that fits like a lock and key with that molecule. These are just like the receptors on the surfaces of your cells. So when the molecule increases to a certain amount, which says something about the number of cells, it locks down into that receptor and information comes into the cells that tells the cells to turn on this collective behavior of making light.
Prvo smo shvatili kako ove bakterije to rade, no zatim smo uključili u ovo biološke alate kako bismo shvatili stvarni mehanizam. I što smo otkrili -- znači ovo bi trebala biti, ponovno, moja stanica bakterije -- je da Vibrio fischeri posjeduje protein -- to je ovaj crveni kvadratić -- to je enzim koji stvara onu malu molekulu hormona -- crveni trokut. I onda kako stanice rastu, sve one otpuštaju tu molekulu u okolinu, tako da tamo ima mnogo molekula. Bakterija također ima receptor na svojoj staničnoj površini koji pristaje kao brava i ključ toj molekuli. Ovi su receptori isti kao i na površini vaših stanica. Kada se broj molekula poveća do određenog iznosa -- što govori ponešto o broju stanica -- on se zaključava unutar toga receptora te u stanicu dolazi informacija koja govori stanici da uključi kolektivno ponašanje za stvaranje svjetlosti.
Why this is interesting is because in the past decade, we have found that this is not just some anomaly of this ridiculous, glow-in-the-dark bacterium that lives in the ocean -- all bacteria have systems like this. So now what we understand is that all bacteria can talk to each other. They make chemical words, they recognize those words, and they turn on group behaviors that are only successful when all of the cells participate in unison. So now we have a fancy name for this: we call it "quorum sensing." They vote with these chemical votes, the vote gets counted, and then everybody responds to the vote.
Ovo je zanimljivo jer smo u prošlom desetljeću otkrili da ovo nije samo neka anomalija ove smiješne, u mraku svjetleće bakterije koja živi u oceanu -- sve bakterije imaju sustav sličan ovomu. Dakle, shvatili smo da sve bakterije mogu međusobno govoriti. Oni stvaraju kemijske riječi, one raspoznaju te riječi, i one uključuju skupna ponašanja koja su uspješna jedino kada sve stanice sudjeluju zajednički. Imamo simpatično ime za ovo, zovemo to kvorumska svijest. Oni glasuju putem ovih kemijskih glasova, glas se zbroji, i zatim svi odgovaraju na izglasano.
What's important for today's talk is we know there are hundreds of behaviors that bacteria carry out in these collective fashions. But the one that's probably the most important to you is virulence. It's not like a couple bacteria get in you and start secreting some toxins -- you're enormous; that would have no effect on you, you're huge. But what they do, we now understand, is they get in you, they wait, they start growing, they count themselves with these little molecules, and they recognize when they have the right cell number that if all of the bacteria launch their virulence attack together, they're going to be successful at overcoming an enormous host. So bacteria always control pathogenicity with quorum sensing. So that's how it works.
Što je važno za današnje izlaganje je to da mi znamo da postoje stotine vrsta ponašanja koja bakterije izvode na ovakav zajednički način. No ono što je vjerojatno za vas najznačajnije jest zaraznost. To nije kao kad par bakterija dospije u vas i počinju lučiti neke otrove -- vi ste ogromni, to ne bi imalo učinak na vas. Vi ste golemi. Ono što one rade, a sada smo to shvatili, uđu u vas, čekaju, počinju se množiti, prebrojavaju se pomoću ovih malenih molekula, i prepoznaju kada dosegnu pravi broj stanica i kada bi sve bakterije započele svoj napad zajednički, tada bi bile uspješne u svladavanju ogromnog domaćina. Bakterije uvijek kontroliraju patogenost pomoću kvorumske svijesti. Tako to funkcionira.
We also then went to look at what are these molecules. These were the red triangles on my slides before. This is the Vibrio fischeri molecule. This is the word that it talks with. And then we started to look at other bacteria, and these are just a smattering of the molecules that we've discovered. What I hope you can see is that the molecules are related. The left-hand part of the molecule is identical in every single species of bacteria. But the right-hand part of the molecule is a little bit different in every single species. What that does is to confer exquisite species specificities to these languages. So each molecule fits into its partner receptor and no other. So these are private, secret conversations. These conversations are for intraspecies communication. Each bacteria uses a particular molecule that's its language that allows it to count its own siblings.
Zatim smo, također željeli provjeriti što su ove molekule -- to su bili crveni trokutovi na mom prethodnom dijapozitivu. Ovo je molekula Vibrio fisheri. Ovo je riječ pomoću koje govori. Dakle, zatim smo počeli gledati kod drugih bakterija, i ovo je samo manji dio molekula koje smo otkrili. Nadam se da možete vidjeti da su molekule u povezane. Dio s lijeve strane molekula je jednak kod svake vrste bakterija. Međutim, desna strana molekula je malo drugačija kod svake pojedine vrste. U biti, to je ono što daje pojedinoj vrsti posebnost njihovih jezika. Svaka molekula se uklapa s receptorom svoga partnera i nijednog više. Znači, ovo su osobni, tajni razgovori. Ovi razgovori služe za komunikaciju među vrstama. Svaka bakterija koristi posebnu molekulu koja je njen jezik, i koja omogućuje prebrojavanje svoje subraće.
Once we got that far, we thought we were starting to understand that bacteria have these social behaviors. But what we were really thinking about is that most of the time, bacteria don't live by themselves, they live in incredible mixtures, with hundreds or thousands of other species of bacteria. And that's depicted on this slide. This is your skin. So this is just a picture -- a micrograph of your skin. Anywhere on your body, it looks pretty much like this. What I hope you can see is that there's all kinds of bacteria there. And so we started to think, if this really is about communication in bacteria, and it's about counting your neighbors, it's not enough to be able to only talk within your species. There has to be a way to take a census of the rest of the bacteria in the population.
Kad smo stigli tako daleko mislili smo da smo počinjali razumijevati da bakterije imaju takva društvena ponašanja. No ono što smo zaista mislili je da većinu vremena bakterije ne žive same, one žive u nevjerojatnim mješavinama, sa stotinama i tisućama drugih vrsta bakterija. I to je opisano na ovom dijapozitivu. Ovo je vaša koža. Ovo je samo slika -- mikrograf vaše kože. Posvuda na vašem tijelu, ovo izgleda približno isto, i nadam se da možete vidjeti da tamo ima svih vrsta bakterija. I tako, počeli smo razmišljati je li ovo stvarno do komunikacije kod bakterija, i da se radi o prebrojavanju susjeda, nije dovoljno moći razgovarati samo unutar svoje vrste. Mora postojati način kako načiniti popis ostalih bakterija unutar populacije. Tada smo se vratili molekularnoj biologiji
So we went back to molecular biology and started studying different bacteria. And what we've found now is that, in fact, bacteria are multilingual. They all have a species-specific system, they have a molecule that says "me." But then running in parallel to that is a second system that we've discovered, that's generic. So they have a second enzyme that makes a second signal, and it has its own receptor, and this molecule is the trade language of bacteria. It's used by all different bacteria, and it's the language of interspecies communication. What happens is that bacteria are able to count how many of "me" and how many of "you." And they take that information inside, and they decide what tasks to carry out depending on who's in the minority and who's in the majority of any given population.
i počeli proučavati različite bakterije, i onda smo otkrili da su, zapravo, bakterije višejezične. Sve one imaju sustav poseban za svoju vrstu -- imaju molekulu koja govori "ja". No uz taj, postoji paralelni, drugi sustav kojega smo otkrili, a on je opći. Dakle, imaju drugi enzim koji stvara drugi signal a on ima svoj vlastiti receptor, i ova molekula je jezik razmjene između bakterija. Koriste je sve vrste bakterija i to je jezik komunikacije među vrstama. Ono što se događa je da su bakterije u stanju prebrojati koliko ima "mene", a koliko "tebe". One unose informaciju, i onda odlučuju koji zadatak poduzeti u ovisnosti tko je u manjini, a tko u većini u bilo kojoj populaciji.
Then, again, we turned to chemistry, and we figured out what this generic molecule is -- that was the pink ovals on my last slide, this is it. It's a very small, five-carbon molecule. And what the important thing is that we learned is that every bacterium has exactly the same enzyme and makes exactly the same molecule. So they're all using this molecule for interspecies communication. This is the bacterial Esperanto.
Onda, ponovno se okrećemo kemiji, i shvatamo kakva je ova opća molekula -- što su bile ružičaste elipse na mom zadnjem dijapozitivu, to je ta. To je veoma mala petoerovalentna ugljikova molekula. Važna stvar koju smo naučili je da svaka bakterija ima potpuno isti enzim i tvori potpuno istu molekulu. Znači, oni koriste ovu molekulu za komunikaciju između vrsta. To je bakterijski Esperanto.
(Laughter)
(Smijeh)
So once we got that far, we started to learn that bacteria can talk to each other with this chemical language. But we started to think that maybe there is something practical that we can do here as well. I've told you that bacteria have all these social behaviors, that they communicate with these molecules. Of course, I've also told you that one of the important things they do is to initiate pathogenicity using quorum sensing. So we thought: What if we made these bacteria so they can't talk or they can't hear? Couldn't these be new kinds of antibiotics?
Kad smo već tako daleko dogurali, počeli smo shvačati da bakterije mogu međusobno razgovarati putem tog kemijskog jezika. Međutim, počeli smo misliti da možda postoji nešto praktično što ovdje možemo učiniti. Već sam vam rekla da bakterije uistinu imaju različita društvena ponašanja, one komuniciraju pomoću ovih molekula. Naravno, isto sam vam već rekla da je jedna od važnijih stvari što one čine da izazivaju patogeni učinak koristeći kvorumsku svijest. Mislili smo, što ako prisilimo ove bakterije tako da ne mogu govoriti ili ne mogu čuti? Zar ne bi one mogle postati nove vrste antibiotika?
And of course, you've just heard and you already know that we're running out of antibiotics. Bacteria are incredibly multi-drug-resistant right now, and that's because all of the antibiotics that we use kill bacteria. They either pop the bacterial membrane, they make the bacterium so it can't replicate its DNA. We kill bacteria with traditional antibiotics, and that selects for resistant mutants. And so now, of course, we have this global problem in infectious diseases. So we thought, what if we could sort of do behavior modifications, just make these bacteria so they can't talk, they can't count, and they don't know to launch virulence?
Svakako, upravo ste čuli i već znate da nam ponestaje antibiotika. Bakterije su trenutno veoma otporne na različite vrste lijekova, a to je stoga što svi antibiotici koje koristimo ubijaju bakterije. Oni izazivaju pucanje bakterijske membrane, koje tvore bakteriju tako da ona ne može replicirati svoju DNA. Ubijamo bakterije tradicionalnim antibioticima a to selekcionira otporne mutante. I naravno sada imamo ovaj globalni problem sa zaraznim bolestima. Pomislili smo, što kad bismo mogli načiniti neku vrstu promjene ponašanja, jednostavno prisiliti bakterije da ne mogu govoriti, da ne mogu brojati, i time da ne znaju započeti zarazu.
So that's exactly what we've done, and we've sort of taken two strategies. The first one is, we've targeted the intraspecies communication system. So we made molecules that look kind of like the real molecules, which you saw, but they're a little bit different. And so they lock into those receptors, and they jam recognition of the real thing. So by targeting the red system, what we are able to do is make species-specific, or disease-specific, anti-quorum-sensing molecules. We've also done the same thing with the pink system. We've taken that universal molecule and turned it around a little bit so that we've made antagonists of the interspecies communication system. The hope is that these will be used as broad-spectrum antibiotics that work against all bacteria.
E pa točno to smo i učinili, i primijenili dvije strategije. Prva je da smo napali komunikacijski sustav među vrstama. Napravili smo molekule koje su nalikovale stvarnim molekulama -- koje ste vidjeli -- no ipak su malo drugačije. One se prihvate na ove receptore, i pobrkaju raspoznavanje stvarnih stvari. Napadom na crveni sustav, u stanju smo učiniti posebnu vrstu, ili molekule anti-kvorumske svijesti posebnih bolesti. Isto to smo uradili i sa ružičastim sustavom. Uzeli smo tu univerzalnu molekulu te je malo promijenili i time smo načinili suparnike komunikacijskom sustavu među vrstama. Nadati se da će ovo biti primijenjeno na različite vrste antibiotika koji djeluju protiv bakterija.
And so to finish, I'll show you the strategy. In this one, I'm just using the interspecies molecule, but the logic is exactly the same. So what you know is that when that bacterium gets into the animal -- in this case, a mouse -- it doesn't initiate virulence right away. It gets in, it starts growing, it starts secreting its quorum-sensing molecules. It recognizes when it has enough bacteria that now they're going to launch their attack, and the animal dies. And so what we've been able to do is to give these virulent infections, but we give them in conjunction with our anti-quorum-sensing molecules. So these are molecules that look kind of like the real thing, but they're a little different, which I've depicted on this slide. What we now know is that if we treat the animal with a pathogenic bacterium -- a multi-drug-resistant pathogenic bacterium -- in the same time we give our anti-quorum-sensing molecule, in fact, the animal lives.
Na kraju samo ću vam pokazati strategiju. U ovoj prvoj, koristim samo molekulu među vrstama, no logika je potpuno ista. Ono što znate je da kada bakterija uđe u životinju, u ovom slučaju, u miša, ne uzrokuje zarazu odmah. Ona uđe, počinje rasti, i počinje lučiti svoje molekule kvorumske svijesti. Prepozna kada ima dovoljno bakterija i tada one započinju svoj napad, i životinja umire. Ono što smo u mogučnsti učiniti je dati ove infekcije, ali zajedno sa našim molekulama anti-kvorumske svijesti -- znači ove molekule nalikuju na prave, osim što su malo drugačije, kao što sam opisala na ovom dijapozitivu. Sada znamo da kada tretiramo životinju patogenim bakterijama -- otpornima na različite lijekove -- istovremeno im dajući i naše molekule anti-kvorumske svijesti, životinja preživljava.
And so we think that this is the next generation of antibiotics, and it's going to get us around, at least initially, this big problem of resistance. What I hope you think is that bacteria can talk to each other, they use chemicals as their words, they have an incredibly complicated chemical lexicon that we're just now starting to learn about. Of course, what that allows bacteria to do is to be multicellular. So in the spirit of TED, they're doing things together because it makes a difference. What happens is that bacteria have these collective behaviors, and they can carry out tasks that they could never accomplish if they simply acted as individuals.
Smatramo da je ovo sljedeća generacija antibiotika i da će barem u početku uspjeti zaobići taj veliki problem otpornosti. Nadam se da razumijete, da bakterije mogu govoriti međusobno, koristeći pri tom kemijske spojeve kao riječi da imaju nevjerojatno složen kemijski rječnik, i da tek sada počinjemo to spoznavati. Naravno, ono što omogućuje bakteriji da to čini je višestaničnost. Dakle, u duhu TED-a oni ovo čine zajednički jer to omogućuje razliku. Ono što se događa, je da bakterije imaju ta kolektivna ponašanja, i one mogu izvršiti zadatke koje nikada ne bi mogle izvršiti kad bi djelovale pojedinačno.
What I would hope that I could further argue to you is that this is the invention of multicellularity. Bacteria have been on the earth for billions of years; humans, couple hundred thousand. So we think bacteria made the rules for how multicellular organization works. And we think by studying bacteria, we're going to be able to have insight about multicellularity in the human body. So we know that the principles and the rules, if we can figure them out in these sort of primitive organisms, the hope is that they will be applied to other human diseases and human behaviors as well. I hope that what you've learned is that bacteria can distinguish self from other. So by using these two molecules, they can say "me" and they can say "you." And again, of course, that's what we do, both in a molecular way, and also in an outward way, but I think about the molecular stuff.
Nadam se nadalje da vas mogu uvjeriti da je ovo izum višestaničnosti. Bakterije su na Zemlji već milijardama godina. Ljudi -- tek nekoliko stotina tisuća. Smatramo da su bakterije stvorile pravila kako da višestanični organizmi funkcioniraju. Proučavajući bakterije, mislimo da ćemo steći uvid u to kako funkcionira višestaničnost u ljudskom tijelu. Znamo da će se načela i pravila, ako ih shvatimo u ovim primitivnim organizmima, moći primijeniti pri ljudskim oboljenjima i kod ljudskog ponašanja, također. Nadam se da ste naučili da bakterija može razlikovati sebe od ostalih. Koristeći ove dvije molekule one mogu reći "ja" i mogu reći "ti". Opet, dakako, to je ono što mi činimo, kako na molekularnoj razini, tako i na spoljašnjoj, no, ja ipak razmišljam o molekularnim stvarima.
This is exactly what happens in your body. It's not like your heart cells and kidney cells get all mixed up every day, and that's because there's all of this chemistry going on, these molecules that say who each of these groups of cells is and what their tasks should be. So again, we think bacteria invented that, and you've just evolved a few more bells and whistles, but all of the ideas are in these simple systems that we can study.
Ovo je točno ono što se događa u vašem tijelu. Nije kao kad se stanice vašega srca ili bubrega pomiješaju svakodnevno, a to je zato što se sva ta kemija odvija, ove molekule govore koja je koja od ovih skupina stanica, i koja bi im trebala biti zadaća. Ponovno, mislimo da su bakterije to izumile, a vi ste se samo razvili dalje, no, sve ideje se nalaze u ovim jednostavnim sustavima koje možemo proučavati.
And the final thing is, just to reiterate that there's this practical part, and so we've made these anti-quorum-sensing molecules that are being developed as new kinds of therapeutics. But then, to finish with a plug for all the good and miraculous bacteria that live on the earth, we've also made pro-quorum-sensing molecules. So we've targeted those systems to make the molecules work better. So remember, you have these 10 times or more bacterial cells in you or on you, keeping you healthy. What we're also trying to do is to beef up the conversation of the bacteria that live as mutualists with you, in the hopes of making you more healthy, making those conversations better, so bacteria can do things that we want them to do better than they would be on their own.
Zadnja stvar je, da još jednom ponovim da postoji i ovaj praktični dio, znači načinili smo ove molekule sa anti-kvorum sviješću koje se razvijaju kao nova vrsta lijekova. No onda, da završim i da se ponovno uključim na sve dobre i čudesne bakterije koje žive na Zemlji, također smo napravili i molekule za kvorum svijest. Znači, napadali smo te sustave kako bi primorali molekule da rade bolje. Sjetite se da imate ovih 10 puta više bakterijskih stanica u vama i na vama, i koje vas održavaju zdravima. Ono što još pokušavamo napraviti je da pojačamo razgovor bakterija koje žive zajedno s vama, u nadi da vas načinimo još zdravijima, čineći te razgovore boljima, znači bekterije mogu činiti stvari koje mi želimo da rade bolje nego bi to same činile.
Finally, I wanted to show you -- this is my gang at Princeton, New Jersey. Everything I told you about was discovered by someone in that picture. And I hope when you learn things, like about how the natural world works -- I just want to say that whenever you read something in the newspaper or you hear some talk about something ridiculous in the natural world, it was done by a child. So science is done by that demographic. All of those people are between 20 and 30 years old, and they are the engine that drives scientific discovery in this country. And it's a really lucky demographic to work with.
Konačno, želim vam pokazati ovo je moje društvo na Princeton-u, New Jersey. Sve o čemu sam vam govorila je otkrio netko s ove slike. Nadam se da kada naučite neke stvari, kao na primjer kako prirodan svijet funkcionira -- želim samo kazati da kadgod pročitate nešto u novinama ili čujete neko izlaganje o nečem smiješnom u prirodnom svijetu to je napravilo neko dijete. Nauka se stvara od takve populacije. Svi ovi ljudi su između 20 i 30 godina starosti, i oni su stroj koji pokreće znanstvena otkrića u ovoj zemlji. Stvarno je to zahvalna populacija za rad.
(Applause)
Ja postajem sve starija i starija, a oni ostaju uvijek istih godina,
I keep getting older and older, and they're always the same age. And it's just a crazy, delightful job. And I want to thank you for inviting me here, it's a big treat for me to get to come to this conference.
i ovo je jednostavno ludo ugodan posao. Željela bih vam se zahvaliti što ste me pozvali ovdje. Za mene je izuzetno uživanje bio dolazak na ovu konferenciju. (Pljesak)
(Applause)
Thanks.
Hvala.
(Applause)
(Pljesak)