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   Models of Immune response to Helicobacter pylori

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Gregg S. Davis, Simeone Marino, Carl F. Marrs, Janet R. Gilsdorf, Suzanne Dawid, Denise E. Kirschner, Phase variation and host immunity against high molecular weight (HMW) adhesins shape population dynamics of nontypeable Haemophilus influenzae within human hosts, Journal of Theoretical Biology 355 (2014) 208-218, DOI: 10.1016/j.jtbi.2014.04.010, PMID: 24747580, PMCID: 4089356

Anna Maria Spagnuolo, Victor DiRita, Denise Kirschner, A model for Vibrio cholerae colonization of the human intestine. Journal of Theoretical Biology (2011), pp. 247-258, DOI: 10.1016/j.jtbi.2011.08.028, PMID: 21903104, PMCID: 3191311

Martin J. Blaser, Denise Kirschner The equilibria that allow bacterial persistence in human hosts . Nature, Vol 449, j18, October 2007, pp 483-489, PMID: 17943121, PMCID: (exempt)

Niyaz Ahmed, of the Pathogen Evolution Laboratory, Centre for DNA Fingerprinting and Diagnostics, India, gives his comments on the article at
This is a provocative yet legitimate proposal on how pathogenic bacteria adapt to their co-evolved hosts across a wide array of conditions linked to biology of both the host and pathogen, over huge evolutionary timescales. The authors focus on the concept that persistence represents finely negotiated, well balanced host- microbial interests, culminating in a long-term equilibrium whose maintenance requires a series of evolved, nested equilibria leading to the overall homeostasis. To support their assumption the authors harness observed pathobiology of three dreaded pathogens (H. pylori, S. typhi and M. tuberculosis). Based on the fact that genomic and biological features of these 'specialist' bacteria are quite diverse, authors generalize their model for other pathogens as well. If it is so, this model may also fit to commensals and other 'generalist' bacteria who might have accompanied humans in various capacities throughout their association. This dogma may therefore be relevant in understanding acquisition and/or attenuation of virulence with the change in human history and ecology. Although this is a largely speculative treatise, I am sure it will provide a foundation for future experimental evidence.
Raymond Mejia, of the National Heart, Lung and Blood Institute (NHLBI), and the National Institutes of Health (NIH), gives his comments on the article at
This study uses a mathematical model to explain bacterial persistence in a host population. Symbiosis is characterized by existence of evolutionary stable states that permit homeostasis. The model is applied to three bacteria with human hosts, H. pylori, S. typhi, and M. tuberculosis, and can be utilized to investigate how virulence may vary with changes in human ecology.

Joseph, I., Kirschner, D., A Model for the Study of Helicobacter Pylori Interaction with Human Gastric Acid Secretion . Journal of Theoretical Biology 228:55-80, 2004, PMID: 15064083, PMCID: (exempt)

Sud, D., Joseph, I., Kirschner, D., Predicting Efficacy of Proton Pump Inhibitors in Regulating Gastric Acid Secretion. Journal of Biological Systems, Vol. 12, No. 1, pg 1-34, 2004, PMID: n/a, PMCID: (exempt)

Marino, S., Ganguli, S., Joseph, I.M.P., Kirschner, D.E., The Importance of an Inter-compartmental Delay in a Model for Human Gastric Acid Secretion . Bulletin of Math. Biology, 65:963-990, 2003, PMID: 14607284, PMCID: (exempt)

Errata, Marino et al.

Joseph, I.M., Y. Zavros, J.L. Merchant, and D. Kirschner, A model for integrative study of human gastric acid secretion . J Appl Physiology 94, pg. 1602-1619, 2003, PMID: 12433865, PMCID: (exempt)

Denise E. Kirschner, Reconstructing Microbial Pathogenesis ASM News Vol 67, Num. 11, pp. 566-573, 2001, PMID: n/a, PMCID: (exempt)

Kirschner D and Freter R. Mathematical Models of Persistent Bacterial Infections. In: Nataro J, Blaser MJ, and Cunningham-Rungles S. (eds): Persistant Bacterial Infections, for ASM Press Publications, Washington, DC, pp. 79-99, 2000, PMID: n/a, PMCID: (exempt)

Falk P, Syder A, Guruge J, Kirschner D, Blaser M and Gordon J. Theoretical and experimental approaches for studying factors that define the relationship between Heliobacter pylori and its host. Trends in Microbiol Vol 8, pps 321-329, July 2000, PMID: 10878767, PMCID: (exempt)

Blaser MJ and Kirschner D. Dynamics of Helicobacter pylori colonization in relation to the host immune response. PNAS, 96:8359-8364, 1999, PMID: 10411880, PMCID: 17522

Kirschner D and Blaser M. The dynamics of Heliocobacter pylori infection of the human stomach. J Theor Biol, 176:281-290, 1995, PMID: 7475116, PMCID: (exempt)



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