Dosage and Dose Schedule Screening of Drug Combinations in Agent-Based Models Reveals Hidden Synergies

Frontiers in Physiology
Lisa C Barros de Andrade E SousaEdda Klipp

Abstract

The fungus Candida albicans is the most common causative agent of human fungal infections and better drugs or drug combination strategies are urgently needed. Here, we present an agent-based model of the interplay of C. albicans with the host immune system and with the microflora of the host. We took into account the morphological change of C. albicans from the yeast to hyphae form and its dynamics during infection. The model allowed us to follow the dynamics of fungal growth and morphology, of the immune cells and of microflora in different perturbing situations. We specifically focused on the consequences of microflora reduction following antibiotic treatment. Using the agent-based model, different drug types have been tested for their effectiveness, namely drugs that inhibit cell division and drugs that constrain the yeast-to-hyphae transition. Applied individually, the division drug turned out to successfully decrease hyphae while the transition drug leads to a burst in hyphae after the end of the treatment. To evaluate the effect of different drug combinations, doses, and schedules, we introduced a measure for the return to a healthy state, the infection score. Using this measure, we found that the addition of a transition...Continue Reading

References

Sep 23, 1997·Cell·H J LoG R Fink
May 19, 2000·Infection and Immunity·Q T PhanS G Filler
Dec 25, 2003·Antimicrobial Agents and Chemotherapy·Mahomed-Yunus S MoosaRobert A Akins
Oct 8, 2004·Eukaryotic Cell·Michael C LorenzGerald R Fink
Feb 2, 2006·The Journal of Antimicrobial Chemotherapy·C CharlierO Lortholary
May 19, 2007·Medical Mycology·Joshua PerlrothBrad Spellberg
Jun 24, 2008·Journal of Theoretical Biology·Simeone MarinoDenise E Kirschner
Mar 7, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·J Christian J RayDenise E Kirschner
Oct 15, 2009·European Journal of Pharmacology·Andrzej SwierniakJaroslaw Smieja
Feb 18, 2010·Information Sciences·Amy L BauerAlan S Perelson
Mar 30, 2010·Nature Reviews. Microbiology·Anton Y PelegEleftherios Mylonakis
Sep 14, 2010·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Gary AnYoram Vodovotz
Mar 29, 2011·Advances in Dental Research·J R Naglik, D Moyes
Aug 2, 2011·Microbes and Infection·Julian R NaglikBernhard Hube
Dec 14, 2011·Expert Review of Anti-infective Therapy·Ilse D JacobsenBernhard Hube
Dec 14, 2011·Nature Reviews. Microbiology·Neil A R GowMihai G Netea
Jan 19, 2012·Infection and Immunity·Shih-Chin ChengMihai G Netea
Mar 15, 2012·Immunologic Research·Fabien Cottier, Norman Pavelka
May 5, 2012·Frontiers in Microbiology·Christian TokarskiStefan Schuster
Jun 12, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joshua T MattilaJoanne L Flynn
Jun 27, 2013·Theoretical Biology & Medical Modelling·Jun WangXiaobo Zhou
Jul 3, 2013·Journal of Theoretical Biology·Chang GongD Kirschner
Dec 18, 2013·Science·Dirk Brockmann, Dirk Helbing
Jan 1, 2014·Eukaryotic Cell·Melanie WellingtonDamian J Krysan
Feb 28, 2014·Nature·Marta Luksza, Michael Lässig
Mar 13, 2014·Journal of Theoretical Biology·Munju KimKatarzyna A Rejniak
May 9, 2014·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Denise E KirschnerJennifer J Linderman
May 28, 2014·BioMed Research International·Ferdinando ChiacchioFrancesco Pappalardo
Nov 26, 2014·Infection and Immunity·Eric F KongMary Ann Jabra-Rizk
Mar 20, 2015·Disease Models & Mechanisms·Sascha BrunkeDominique Ferrandon

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