bistability and bacterial infections双稳态和细菌感染.pdfVIP

Bistability and Bacterial Infections 1 2 3 Roy Malka , Eliezer Shochat , Vered Rom-Kedar * 1 Department of Computer Science and Applied Mathematics, The Weizmann Institute of Science, Rehovot, Israel, 2 Pharma Research and Early Development, Hoffmann- La Roche, Basel, Switzerland, 3 The Estrin Family Chair of Computer Science and Applied Mathematics, Department of Computer Science and Applied Mathematics, The Weizmann Institute of Science, Rehovot, Israel Abstract 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