Bistability and bacterial infections.
Bacterial infections occur when the natural host defenses are overwhelmed by invading bacteria. The main component of the host defense is impaired when neutrophil count or function is too low, putting the host at great risk of developing an acute infection. In people with intact immune systems, neutrophil count increases during bacterial infection. However, there are two important clinical cases in which they remain constant: a) in patients with neutropenic-associated conditions, such as those undergoing chemotherapy at the nadir (the minimum clinically observable neutrophil level); b) in ex vivo examination of the patient's neutrophil bactericidal activity. Here we study bacterial population dynamics under fixed neutrophil levels by mathematical modelling. We show that under reasonable biological assumptions, there are only two possible scenarios: 1) Bacterial behavior is monostable: it always converges to a stable equilibrium of bacterial concentration which only depends, in a gradual manner, on the neutrophil level (and not on the initial bacterial level). We call such a behavior type I dynamics. 2) The bacterial dynamics is bistable for some range of neutrophil levels. We call such a behavior type II dynamics. In the bistable case (type II), one equilibrium corresponds to a healthy state whereas the other corresponds to a fulminant bacterial infection. We demonstrate that published data of in vitro Staphylococcus epidermidis bactericidal experiments are inconsistent with both the type I dynamics and the commonly used linear model and are consistent with type II dynamics. We argue that type II dynamics is a plausible mechanism for the development of a fulminant infection.
Malka
Roy
R
Department of Computer Science and Applied Mathematics, The Weizmann Institute of Science, Rehovot, Israel.
Shochat
Eliezer
E
Rom-Kedar
Vered
V
D001419:Bacteria / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology*
Nat Rev Immunol. 2006 Mar;6(3):173-82
16498448
J Dairy Sci. 2006 Sep;89(9):3455-65
16899679
Immunology. 1979 Jun;37(2):453-65
381182
Bull Math Biol. 2010 May;72(4):765-79
19851812
Math Biosci. 2008 Jul-Aug;214(1-2):73-80
18547594
Blood. 1984 Sep;64(3):635-41
6087960
J Math Biol. 2004 Feb;48(2):218-42
14745511
J Theor Biol. 2006 Sep 7;242(1):237-56
16616206
J Theor Biol. 2001 Jul 7;211(1):11-27
11407888
PLoS One. 2009;4(4):e5234
19381301
Shock. 2005 Jul;24(1):74-84
15988324
Appl Environ Microbiol. 1990 Jun;56(6):1875-81
16348228
J Theor Biol. 2004 Sep 21;230(2):145-55
15321710
Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8289-94
12060772
Ann Intern Med. 1966 Feb;64(2):328-40
5216294
Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8697-702
16735474
Blood Cells Mol Dis. 2001 Nov-Dec;27(6):1000-4
11831866
J Exp Med. 2004 Sep 6;200(5):613-22
15353554
J Lab Clin Med. 1981 Dec;98(6):938-48
6796635
J Theor Biol. 2006 Sep 7;242(1):220-36
16584750
Clin Cancer Res. 2008 Oct 15;14(20):6354-63
18927273
Clin Immunol. 2008 Oct;129(1):103-14
18708296
J Theor Biol. 1976 May 7;58(1):197-205
957682
PLoS One. 2008;3(12):e4036
19112501
Cancer. 1997 Mar 15;79(6):1150-7
9070492
J Lab Clin Med. 1976 Aug;88(2):316-27
956687
J Dairy Sci. 2004 Nov;87(11):3716-24
15483155
J Hyg (Lond). 1980 Jun;84(3):457-65
7052225
J Theor Biol. 1974 Sep;47(1):177-88
4459580
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1822-7
14766974
Methods Mol Biol. 2007;412:319-32
18453121
Nat Cell Biol. 2003 Apr;5(4):346-51
12629549