[MUSIC] Hello, Oana and Peter. >> Hello. >> Hello. >> Today we'll talk about, the problems of treating chronic infections and why the host defense seems to be not working probably. And let me start with you, Oana. What seemed to be the problem regarding treating chronic bacterial infections? >> Well, obvious the problem is that in chronic infections the bacteria are grown in biofilms. And the, as we know from the in vitro studies, the bacteria growing in biofilms, they have different metabolic activities. Basically, they divide very slowly or not at all in some of the layers. And we know that the efficacy of antibiotics that we have been studying on planktonic cells. It also depends on the metabolic activity of the cells. So probably the activity of antibiotics that we study and we know it from in planktonic, un-planktonic cultures. It does not, reflect how the antibiotics are working on biofilms. >> Mm-hm. >> And actually, the tolerance of biofilms, to antibiotics is part of the definition of biofilms. So it is the intrinsic characteristics of biofilms that make it very difficult to treat biofilms with the antibiotics we have and with the antibiotics regimes we use for planktonic infections. >> All right. So Peter, antibiotics do not seem to work that well in chronic infections. But why can't our own host defense not eradicate the bacteria? >> That's a good question, and we don't have the complete answer yet. But we know that a bacterial species is much more tolerant against the host response. And the bacteria are able to form the biofilms. We know some mechanisms that these biofilms are able to protect themselves against the host response. For instance by increased production of rem lipeds. Which will last effective sites of the host response. And apparently within this biofilm the host response are not detecting all of the bacteria. They, they can't, the host response cannot account for the deeper layers of bacteria. So the host response is probably not intense enough. But unfortunately, it goes on and it has collateral damaging effects. >> Mm-hm, >> You should also notice that these host defense are, apparently, completely healthy. Because the patients do not have signs of acute infections, just these biofilm. >> Yeah, and supposedly why, why is, is this so different than acute infections because here it seems that we can treat the bacteria if they are not eradicated by the whole defense. >> Well, [COUGH] as I said, it's probably the structure of the biofilms. I think that we also have a problem in detecting defective antibiotics. Because we don't have diagnostic methods that are reliable. >> And this is a definitely field that we should work on, because if we want to design a better antibiotic strategy we need to have a method to measure how our antibiotic treatment works. And I think that this is also the part of the problem. >> Mm-hm. Any thought? >> Yeah. I think, that, part of the problem is that the host response is prolonged against the biofilm. And it's a type of a low inflammatory great response. Apparently, the patient will not notice it before the inflammation has resulted in too much tissue damage. >> So, in this course we also, we talked about, yeah, that old bacteria can, can form biofilms. But, but is it the same bacteria which cause both chronic infections and acute infections? >> Yeah basically the, all microorganisms or many of them can do both things. So the factor that is important for the course of infection if it is an acute or a chronic infection is probably the host factor. >> Mm-hm. >> If you have, implants basically, of course, all the implants associated infections [INAUDIBLE] Or these cystic fibrosis chronic lung infection, where the innate immune system is not working. So the bacteria have the ability to do it. But it's just a question of opportunity, to have the opportunity to do it. >> Yeah. >> Can we do anything about it? >> Oh, [LAUGH] at least we can attack the planktonic part of the infection affectively with, antibiotics >> But the- >> And probably to assume or how to find out the risk factor and the risk patients. And it's possible to do prophylactic treatment for some, in some cases. Like for example, in surgery of the bones, surgery with the risk of having an infection of the bone. Which is actually biofilm infectious, very high, then you can prevent and do something about it by prophylactic treatment. >> Okay. >> So [COUGH]. >> And what, what do you think will the problem of chronic infections increase over the years? >> I think that we know that these biofilm infections are associated with device incorporated into, devices incorporated into the patients. And I think with time we'll have incorporated much more devices >> Mm-hm >> To patients, and it will increase. And there's also an association with lifestyle diseases, which apparently will also increase. >> That's what we have this increasing problem of antibiotic resistant bacterial so if you have a planktonic infection with an antibiotic resistant microorganism and we are not able to treat it. That and the risk factors are there for biofilm infections then it's probably also a way or reason for an increase in number of biofilm infections in the future. >> Okay, so >> The best thing probably to do to prevent it in the first place, if we somehow set better diagnostics- >> I, I think so because we I mean, now we, we actually don't know. I, it is just a treatment that or an infection that we can treat and then the patient probably has some risk factors that we can identify. And then it might be a biofilm infection. And then we treat it longer time and high antibiotic concentrations and so on but I don't think that we have completely, such reliable method to know if it's, they are there, the bad things. Where they are and so on. >> And also, as you said, they're silent almost in the beginning. So it takes a long time before you start to have pain? >> Yes. Yeah. >> Yeah, then it's maybe too late. >> Yeah? >> Yeah. >> Yeah, the tissue damage is already there. >> Okay. So we still have a lot to do. >> I think so, yeah. >> All right. Thank you. >> Thank you, Thomas. >> Thank you. [MUSIC]
