Indirect Fitness Benefits Enable the Spread of Host Genes Promoting Costly Transfer of Beneficial Plasmids

Abstract

Bacterial genes that confer crucial phenotypes, such as antibiotic resistance, can spread horizontally by residing on mobile genetic elements (MGEs). Although many mobile genes provide strong benefits to their hosts, the fitness consequences of the process of transfer itself are less clear. In previous studies, transfer has been interpreted as a parasitic trait of the MGEs because of its costs to the host but also as a trait benefiting host populations through the sharing of a common gene pool. Here, we show that costly donation is an altruistic act when it spreads beneficial MGEs favoured when it increases the inclusive fitness of donor ability alleles. We show mathematically that donor ability can be selected when relatedness at the locus modulating transfer is sufficiently high between donor and recipients, ensuring high frequency of transfer between cells sharing donor alleles. We further experimentally demonstrate that either population structure or discrimination in transfer can increase relatedness to a level selecting for chromosomal transfer alleles. Both mechanisms are likely to occur in natural environments. The simple process of strong dilution can create sufficient population structure to select for donor ability. Another mechanism observed in natural isolates, discrimination in transfer, can emerge through coselection of transfer and discrimination alleles. Our work shows that horizontal gene transfer in bacteria can be promoted by bacterial hosts themselves and not only by MGEs. In the longer term, the success of cells bearing beneficial MGEs combined with biased transfer leads to an association between high donor ability, discrimination, and mobile beneficial genes. However, in conditions that do not select for altruism, host bacteria promoting transfer are outcompeted by hosts with lower transfer rate, an aspect that could be relevant in the fight against the spread of antibiotic resistance.

Plasmid transfer is biased towards close kin in bacteria from natural populations

“…In addition to donor and recipient identity, the main factor controlling transfer rates was the nature of the genetic interaction between them, with transfer towards kin (clone-mates) being more than 10-fold higher than towards non-kin. We therefore extend the pattern identified previously (Dimitriu et al, 2016) to a second plasmid, the broad-host-range RP4.…”

“…This includes non-kin killing by bacteriocins, a form of kin discrimination (Strassmann et al, 2011). Spatial structure, that promotes transfer to kin in the absence of discrimination mechanisms (Dimitriu et al, 2016), can also bias transfer across a population. Indeed the E. coli populations sampled for this study show strong population structure, indicating that opportunities for transfer to plasmid null isolates occur predominantly within genotypes (Medaney et al 2016).…”

“…Moreover, when plasmids confer benefits to their hosts, as with antibiotic exposure for antibiotic resistance plasmids, restricting transfer towards kin will be beneficial to host bacteria. It will also promote indirect selection of efficient donor hosts, through kin selection mechanisms (Dimitriu et al, 2016). However, transfer towards non-kin, that is efficient for some pairs of isolates in our field collection, might also benefit the hosts when the transferred plasmids bear public-good encoding genes (Dimitriu et al, 2014(Dimitriu et al, , 2018, for instance virulence, antibiotic resistance or detoxification genes (Rankin et al, 2010, Raymond et al, 2012.…”

“…It will also promote indirect selection of efficient donor hosts, through kin selection mechanisms (Dimitriu et al, 2016). However, transfer towards non-kin, that is efficient for some pairs of isolates in our field collection, might also benefit the hosts when the transferred plasmids bear public-good encoding genes (Dimitriu et al, 2014(Dimitriu et al, , 2018, for instance virulence, antibiotic resistance or detoxification genes (Rankin et al, 2010, Raymond et al, 2012. More generally, transfer being the highest within kin, together with the observation that plasmids are not at fixation within serotypes (Medaney et al, 2016) suggests that most plasmid dynamics might actually occur not between lineages (the events most easily detected) but within lineages, with recurring loss or counter-selection of plasmid-bearing cells alternating with selection and plasmid transfer.…”

“…Transfer to kin i.e. plasmid donors and recipients belonging to the same genotype, was shown to be particularly efficient across a range of hosts from different strain collections (Dimitriu et al 2016). Biased transfer towards kin can promote higher investment in transfer for beneficial plasmids, which could lead to higher transfer for traits including antibiotic resistance (Dimitriu et al, 2016).…”