[MUSIC] Hello everyone, my name is Lina Cavaco, and I'm here to present this lecture on antimicrobial resistance, the emergence and dissemination of the resistant bacteria. This lecture is actually quite interesting because you will have heard in the news that a new superbug appeared in China for example or in another place in the world and then it's suddenly everyone is worried about it going spreading around the country where we live in and that happens on unfortunately many times. And I'm going to go into that a little bit in detail. First we look into how do these resistance mechanisms appear, how did they emerge, where did they come from. And then looking a bit into the mobile genetic elements. How these elements, these parts of the genome move around so that they move around into different bacteria. How do they can transfer into these different types of bacteria, and how do they transmit so that actually this resistance can spread around. So to start with, where do these resistant genes or elements come from? If you remember from the last lecture, spontaneous mutations are something that can happen in the bacteria itself. Here we are not going to talk about that. We are going to talk about the resistant genes. And, of course, they don't come from nowhere, they come from somewhere and many times they come from some bacteria that are resistant. Maybe they are environmental bacteria or bacteria that are around us. And they by some reason, they do have some resistant elements that could eventually cause resistance to a gene. Of course it's not the final resistant gene that we see in the bacteria that cause disease, sometimes it's just a predecessor to these genes. So, that there is something that looks a little bit like it could be a resistant gene, and many times it comes as I said from some environmental bacteria that is not necessarily causing any disease, is sitting there. And then it has these genes. And because well it's happening in the environment these elements that have potential to cause resistance could be transferred to other bacteria. And here we have for example a round bacteria. And It could eventually be moving around because there are some of these genetic elements that mobilize the resistant genes. It could be that it was sitting in the chromosome, but then a plasmid has taken that part into itself and then is transferring around between other bacteria. So in principle we have some bacteria that are resistant to different resistant genes that exist in nature. And because they have these genetic elements that replicate by themselves and could eventually be transferred, and they can also modify a little bit and become into different structures of plasmids by combining parts. If these genetic elements come into a bacteria that is susceptible, this blue bacteria that is represented here that is not resistant to antibiotics. If at some point there is a transfer of this resistance element to this susceptible bacteria, then this bacteria could become a resistant bacteria. The issue is mainly when this bacteria that is susceptible is the bacteria that causes disease in humans for example or in animals, and that's where the alarm goes on, and it goes in the news. A new super bug of resistant bacteria that is potential causing disease and cannot be treated by the correct antibiotics, or the most used ones, at least, and then we have to go for last resource antibiotics. And this has happened many times. We have seen it in the news. The most recent case of this is this resistance, which is on the very, very last resort antibiotics. And two weeks ago it appeared in China. And when we were looking into our genomes of the bacteria we have in-house here at DTU, we also found it. So, two weeks ago, it was only a problem that was seen once in China, and nowadays, it's everyone in the world looking for them because they might have spread. When we think of this as transfer of resistance between bacteria, it's not only that is happening. People travel, food travels, there's also a lot of dissemination that goes on that way. So when we have these mobile genetic elements, they can disseminate their resistance determinates so the plasmids that carry them go around. They are transferred. If they are plasmids, or transposons, or integrons, or gene cassettes, it's rather similar. They are mobile, so they can be eventually transferred to a different bacteria, and they can move around between bacteria. So in that way, a bacteria that has one resistance can actually acquire more of them and become multi-drug resistant or one element can carry more resistance that it also confers resistance to several drugs and, in that case, what I have, for example, explained in one of the previous lectures about co selective. One plasmid has, let's say, three four resistance, when it goes, it also gives resistance to all three four drugs or classes of drugs. So, it is the system that can go around and this semenate resistance to different species or to different bacteria of the same species around the world. And it happens because ingredients are moved around and people travel, and bacteria themselves are transported around. The horizontal gene transfer is a part of this system because, of course, when they transfer they transfer horizontally, and which is much more efficient than transfer just to the daughter cells. So if one cell is able to share this, this goes much faster. That's why when we are very worriedd in the news about the plasmids mediator. The resistance is much worse than we are just worried about point mutations because of this transfer system. That is very efficient to disseminate. So, if you go a little bit more into the transfer and look into the plasmids for example which is the genetic element that is mostly the case that transports these resistant factors. Know we call them R factors which would we calling R for resistance. That are resistant genes basically. They can carry multiple, so if one plasmids is not exclusive of one resistant gene, it can carry many, can carry more than one at least. And some of these plasmids have the machinery, have the possibility to conjugate which means that they can self go into another cell. However, we also have cryptic plasmids which are small plasmids that normally don't have any resistance factors. But at some point they can acquire. If we look into other genetic mobile elements, we have transposons and insertion sequences, which are basically jumping gene areas. And these would be able to jump from one cell to another and they also can carry multiple resistant genes for example. And they would be able to move from the chromosome to the plasmid sometimes, or back to the chromosome so sometimes it's also moving inside the cell from one area to another. And their basic sequences are they have the enzyme that enables them to jump around and some repeat sequences, insertion sequences that allow them to be recognized. So again integrons is another specific element that is a mobile element. These integrons also could have a single or a group of antimicrobial resistance genes in them. And these genes could include different groups, some are very frequent in the integrons like the sulfonamides and aminoglycosides, but it could include several groups. And these integrons could also sit on the plasmid or sit on the chromosome, and there's some classifications where we try to classify them in classes. For example, depending the integrate enzyme they have, and so on. But basically, they have an integration insertion side, and they would be transporting some antimicrobial resistance genes with them, just like the other mobile genetic elements. So all of these contribute to the possibility of transfer of resistance between one strain and another. And here we just give one example with the plasmids. So we have an E.coli, let's say this is an E.coli with its own genome and one plasmid. And this plasmids has several genes on it. I wouldn't know, but lets say some of them are resistant genes, some are other things. When this strain tries to congregate, lets say the plasma is conjunctive and can't just do it by the machinery that the plasmid has itself, it can actually conjugate, for example, with the salmonella. It's not the same species. It's relatively related to E.coli, and the plasmid is able to replicate in salmonella. So, here, we had the resistant E.coli, which was worrisome already, but maybe this was just a normal E.coli from the intestinal flora. That was not causing much harm even truly it could cause some urinary tract infection or even worser disease but now we have it in salmonella and salmonella is by itself apetigen in humans. It causes gastrointestinal infections and sometimes even blood stream infections. So, suddenly we have it in another species. And that's how it goes. We have resistance determines in one element and it can be transferred from a bacteria to another or a bacteria to even another species. And when we have it in one bacteria, let's say that it would spread to the daughter cells. So this bacteria will divide and it will further divide. All the cells that descend from this one will have it. They will have the plasmid. However, at the same time. They will also be transferring to others. So even more different bacteria will get this. Here that would be similar to each other. And here, we are talking about clonal spread because it's the same clone. It's the same, they all descend from the same bacteria. Here, it's a horizontal spread, so this one doesn't look like this one. It's not clonal at all, it could even be a different species. So and that's why we think that it is really important, and really a threat to treating the infections, that bacteria get, these determinants and transfer the, around. The next lecture will be about selection. Where we can draw some conclusions about what we can do about it. Thank you very much. [MUSIC]
