Amelioration of the Cost of Conjugative Plasmid Carriage in Eschericha coli K12

Abstract

Although plasmids can provide beneficial functions to their host bacteria, they might confer a physiological or energetic cost. This study examines how natural selection may reduce the cost of carrying conjugative plasmids with drug-resistance markers in the absence of antibiotic selection. We studied two plasmids, R1 and RP4, both of which carry multiple drug resistance genes and were shown to impose an initial fitness cost on Escherichia coli. To determine if and how the cost could be reduced, we subjected plasmid-containing bacteria to 1100 generations of evolution in batch cultures. Analysis of the evolved populations revealed that plasmid loss never occurred, but that the cost was reduced through genetic changes in both the plasmids and the bacteria. Changes in the plasmids were inferred by the demonstration that evolved plasmids no longer imposed a cost on their hosts when transferred to a plasmid-free clone of the ancestral E. coli. Changes in the bacteria were shown by the lowered cost when the ancestral plasmids were introduced into evolved bacteria that had been cured of their (evolved) plasmids. Additionally, changes in the bacteria were inferred because conjugative transfer rates of evolved R1 plasmids were lower in the evolved host than in the ancestral host. Our results suggest that once a conjugative bacterial plasmid has invaded a bacterial population it will remain even if the original selection is discontinued.

Harmful behaviour through plasmid transfer: a successful evolutionary strategy of bacteria harbouring conjugative plasmids

“…Moreover, the compensatory mutation occurring in a cell of a specific bacterial strain may not work in another strain (e.g. [38]). Finally, the present paper explains why so many adaptations occur in the chromosome (e.g.…”

“…While compensatory mutations certainly are relevant to plasmid maintenance [26,35,37], one must understand their role in the evolutionary success of conjugative plasmids. Despite facilitating the maintenance of plasmids in cells and their descendants, compensatory mutations occurring in the chromosome are not the best strategy for plasmid maintenance because the transconjugant clone usually has to replicate tens [35] or hundreds of generations [26,38,39] for the compensatory mutation to appear. Moreover, it is unclear why would conjugative plasmids rely on chromosomal compensatory mutations after every transfer event to guarantee evolutionary success.…”

The Perfect Condition for the Rising of Superbugs: Person-to-Person Contact and Antibiotic Use Are the Key Factors Responsible for the Positive Correlation between Antibiotic Resistance Gene Diversity and Virulence Gene Diversity in Human Metagenomes

“…Second, resistance mutations can be beneficial in specific resistance genetic backgrounds, e.g., through epistatic interactions with other chromosomal mutations [25]. Third, while resistance plasmids often impose a fitness cost to their hosts, it has also been observed that plasmids and/or cells need just a few tens or hundreds of bacterial generations to adapt to each other [55][56][57][58][59][60]. Fourth, plasmids sometimes increase the fitness of bacteria that already harbor a resistance mutation [26]; likewise, some resistance mutations increase the fitness of plasmid-bearing cells [26].…”

Modeling the growth of organisms validates a general relation between metabolic costs and natural selection

“…We now partially relax that assumption: we still keep R b the same, but allow the mutant death rate d = − ln(p(t r + δt r ))/(t r + δt r ) to be different than d by some amount δd ≡ d − d. For example if the survival probability p(t) was exponential for the wild-type, p(t) = exp(−ηt), and the rate η was modified in the mutant to η, then δd = η − η. One case where such considerations would come into play would be bacterial strains growing in an environment with antibiotics: a variant that acquired antibiotic resistance would have a lowered death rate, δd < 0, but also possibly non-trivial metabolic costs associated with maintaining the resistance [51][52][53], as discussed in more detail below. Since the mutant now has both altered birth rate r = r + δr = ln(R b )/(t r + δt r ) and death rate d, the population growth equation [Eq.…”