A theoretical and experimental study of the population dynamics of abortive infection Open Access
Manuel, Joshua (Spring 2022)
Published
Abstract
Bacteria have evolved a number of defenses to protect individual cells and populations from infection by bacteriophage (phage). One such defense is abortive infection (abi), a programmed cell death (suicide) which occurs when a bacterium is infected by a lytic (virulent) phage. Using a mathematical-computer simulations model, I explore the a priori conditions under which abi can protect and bacterial populations from infections with lytic phage. To estimate the parameters and test the validity of the predictions of this model, I perform experiments with two abi systems, the Ec48 retron in Escherichia coli, and the abiZ system in Lactococcus lactis. While the results of these experiments are consistent with the predictions of the model, they also suggest that abortive infection is only one step in the defense of these bacteria against phage infection. Within short order of the exposure of these bacteria to phage, envelope resistant mutants emerge and ascend to be the dominant population of bacteria.
Table of Contents
Introduction………………………………………………………………………………………1
The Abortive Infection Systems…………………………………………………………………2
A Model of Abortive Infection…………………………………………………………………..4
Figure 1: Mass-action model diagram…………………………………………………….4
Figure 2: Differential equations for simulations of abortive infection population dynamics…………………………………………………………………………………..4
Table 1: Model parameters for simulations of E. coli, L. lactis and phage population dynamics……………………………………………………………………………….….5
Computer Simulations of Abortive Infection Protection Against Phage Infection………….7
Figure 3: Computer simulation results without envelope resistance……………………...7
Population Dynamics of Abortive Infection Systems in Liquid Culture……………………..9
Figure 4: Experimental results of changes in the densities of bacteria and phage………..9
Figure 5: Efficiency of Plaquing (EOP) of Ec48 retron and abiZ……………………….10
Figure 6: Verification of plasmid pTRK914(pTRK686:abiZ) insertion in L. lactis IL6288…………………………………………………………………………………....11
Short Term Dynamics of abiZ………………………………………………………………….12
Figure 7: Short term impact of abiZ on densities of bacteria and phage………………...12
Computer Simulations of Abortive Infection Accounting for Envelope Resistance and Abi Effectiveness…………………………………………………………………………………….13
Figure 8: Computer simulations with envelope resistance for E. coli…………………...13
Figure 9: Computer simulations with envelope resistance for L. lactis………………….15
Table 2: Average growth rates of abi+ and abi- E. coli and L. lactis with and without envelope resistance………………………………………………………………………16
Discussion……………………………………………………………………………………….16
Materials and Methods…………………………………………………………………………18
Supplemental Material…………………………………………………………………………25
Figure S1…………………………………………………………………………………25
Figure S2…………………………………………………………………………………26
Figure S3…………………………………………………………………………………26
Table S1………………………………………………………………………………….26
Figure S4…………………………………………………………………………………28
Table S2………………………………………………………………………………….28
References……………………………………………………………………………………….29
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