Kaiser2014 - Salmonella persistence after ciprofloxacin treatment

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Model Identifier
BIOMD0000000527
Short description
Kaiser2014 - Salmonella persistence after ciprofloxacin treatment

The model describes the bacterial tolerance to antibiotics. Using a mouse model for Salmonella diarrhea, the authors have found that bacterial persistence occurs in the presence of the antibiotic ciprofloxacin because Salmonella can exist in two different states. One, the fast-growing population that spreads in the host's tissues and the other, slow-growing "persister" population that hide out inside dendritic cells of the host's immune system and cannot be attacked by the antibiotics. However, this can be killed by adding agents that directly stimulate the host's immune defense.

This model is described in the article:

Kaiser P, Regoes RR, Dolowschiak T, Wotzka SY, Lengefeld J, Slack E, Grant AJ, Ackermann M, Hardt WD.
PLoS Biol. 2014 Feb 18;12(2):e1001793.

Abstract:

In vivo, antibiotics are often much less efficient than ex vivo and relapses can occur. The reasons for poor in vivo activity are still not completely understood. We have studied the fluoroquinolone antibiotic ciprofloxacin in an animal model for complicated Salmonellosis. High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN), the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%-20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103⁺CX₃CR1⁻CD11c⁺ dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate, as shown by mathematical analysis of infections with mixed inocula and segregative plasmid experiments. The slow growth was sufficient to explain recalcitrance to antibiotics treatment. Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. Administration of LPS or CpG, known elicitors of innate immune defense, reduced the loads of tolerant bacteria. Thus, manipulating innate immunity may augment the in vivo activity of antibiotics.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L3V1)
Related Publication
  • Cecum lymph node dendritic cells harbor slow-growing bacteria phenotypically tolerant to antibiotic treatment.
  • Patrick Kaiser, Roland R Regoes, Tamas Dolowschiak, Sandra Y Wotzka, Jette Lengefeld, Emma Slack, Andrew J Grant, Martin Ackermann, Wolf-Dietrich Hardt
  • PLoS biology , 2/ 2014 , Volume 12 , Issue 2 , pages: e1001793 , PubMed ID: 24558351
Contributors
Submitter of the first revision: Roland Regoes
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modeller: Roland Regoes

Metadata information

is (2 statements)
BioModels Database BIOMD0000000527
BioModels Database MODEL1312170001

isDescribedBy (1 statement)
PubMed 24558351

hasTaxon (2 statements)
isVersionOf (1 statement)
Gene Ontology response to antibiotic

hasVersion (1 statement)
Human Disease Ontology primary bacterial infectious disease

hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model


Curation status
Curated


Connected external resources