Positive selection and compensatory adaptation interact to stabilize non-transmissible plasmids

Abstract

Plasmids are important drivers of bacterial evolution, but it is challenging to understand how plasmids persist over the long term because plasmid carriage is costly. Classical models predict that horizontal transfer is necessary for plasmid persistence, but recent work shows that almost half of plasmids are non-transmissible. Here we use a combination of mathematical modelling and experimental evolution to investigate how a costly, nontransmissible plasmid, pNUK73, can be maintained in populations of Pseudomonas aeruginosa. Compensatory adaptation increases plasmid stability by eliminating the cost of plasmid carriage. However, positive selection for plasmid-encoded antibiotic resistance is required to maintain the plasmid by offsetting reductions in plasmid frequency due to segregational loss. Crucially, we show that compensatory adaptation and positive selection reinforce each other's effects. Our study provides a new understanding of how plasmids persist in bacterial populations, and it helps to explain why resistance can be maintained after antibiotic use is stopped.

Fitness Costs of Plasmids: a Limit to Plasmid Transmission

“…Plasmids can promote bacterial survival in the presence of antibiotics, but, as we have seen, they can also impose a fitness cost when they enter a new bacterial host. The past few years have witnessed growing interest in the fitness effects of plasmids (21)(22)(23)(24)(25)(26)(27)(28)115), and some of the general principles underlying these effects are now beginning to be identified. However, we still are a long way from understanding the specific molecular basis of these costs or being able to predict plasmid fitness effects in a bacterial host.…”

“…The idea underlying this hypothesis is that even if plasmids produce a cost when they first arrive in a new bacterial host, this cost could be alleviated over time through compensatory mutations in the plasmid and/or the host chromosome (20). In recent years, several studies have analyzed the molecular basis of the cost and compensation of plasmids in bacterial populations (21)(22)(23)(24)(25)(26)(27)(28), generating new models of the existence conditions of plasmids (22,24). These studies evaluate a number of selection, transfer, and compensation regimes that could explain plasmid survival in bacterial populations, and have revealed new evidence about the molecular mechanisms underlying the cost of and adaptation to plasmids.…”

Source–sink plasmid transfer dynamics maintain gene mobility in soil bacterial communities

“…dC dt = ðαC + δQÞ 1 − ðF + P + C + QÞ K − γCðP + QÞ − ΓC − μC, [7] dQ dt = ðβQ− δQÞ 1 − ðF + P + C + QÞ K + γCðP + QÞ+ ΓC + ϕP −μQ, [8] where −ηF represents selection against plasmid-free bacteria that do not have the beneficial genes (24). Similar to the case without positive selection, without a plasmid source the plasmid either remains at fixation in the focal species or is lost by competition with plasmid-free chromosomal mutants, with a narrow range of parameter values resulting in a mixed population of plasmid bearers and plasmid-free chromosomal mutants (Fig.…”

“…Compensatory evolution can ameliorate plasmid cost, thereby weakening selection against the plasmid (7)(8)(9). However, this process is unlikely to stabilize highly unstable plasmids or maintain plasmids in small populations where the rate of plasmid loss is likely to exceed the rate of compensatory evolution.…”

The evolutionary dynamics of integrons in changing environments

“…To gain more knowledge on the basic processes controlling the frequencies of antibiotic resistance in bacterial populations, it is essential that we better understand the population dynamics and evolution of bacteria with acquired MGEs encoding antibiotic resistance in both the presence and absence of antibiotic selective pressures (Johnsen et al, 2009). With the exception of work focusing on plasmids (Bouma and Lenski, 1988;Dahlberg and Chao, 2003;San Millan et al, 2014;Gullberg et al, 2014), surprisingly few studies have addressed the impact of MGE acquisitions on bacterial population dynamics (but see Starikova et al, 2012;Starikova et al, 2013). One class of MGEs with a prominent role in the emergence and spread of antibiotic resistance determinants where studies on the population dynamics following acquisition are particularly limited are the mobile resistance integrons, and especially the class 1 integrons.…”