Noise propagation and amplification in microbial communities with different resistance mechanisms

Abstract

Antimicrobial resistance is a growing concern in the field of microbiology. In a microbial community, the Susceptible Subpopulations (SSs) and the Non-genetically Resistant Subpopulations (NRSs) can switch between each other, and NRSs can mutate to Genetically Resistant Subpopulations (GRSs). In order to quantitatively describe the relationship between noise and signal amplification in the subpopulations, a mathematical model for three subpopulations is proposed in this paper. The gain fluctuation relation is obtained by linear noise approximation of the master equation. Then, through the simulation of these theoretical results, the following conclusions are found. First, the indirect effects of the interaction between subpopulations are much greater than the direct effects, which may be one of the reasons that the infection is difficult to cure. This is consistent with the findings of Zhou et al. and indicates the reliability of our new model. Second, the intrinsic net growth rate of SSs can be chosen as the adjustment parameter, which can effectively exploit or avoid the strong correlation between SSs and the two resistant subpopulations, including NRSs and GRSs. Third, unlike unidirectional cascades, additional intrinsic noise in GRSs can propagate to NRSs. Similarly, although there is no direct interaction between SSs and GRSs, additional intrinsic noise in GRSs can propagate to SSs, and vice versa. Finally, both total noise and adjusted noise exhibit similar amplification properties in this population. It is worth noting that the noise is consistently amplified from NRSs to GRSs. These findings may provide new insights into antimicrobial therapy.