Details

Autor(en) / Beteiligte

• Yano, Hirokazu
• Wegrzyn, Katarznya
• Loftie‐Eaton, Wesley
• Johnson, Jenny
• Deckert, Gail E.
• Rogers, Linda M.
• Konieczny, Igor
• Top, Eva M.

Titel

Evolved plasmid‐host interactions reduce plasmid interference cost

Ist Teil von

• Molecular microbiology, 2016-09, Vol.101 (5), p.743-756

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Summary Antibiotic selection drives adaptation of antibiotic resistance plasmids to new bacterial hosts, but the molecular mechanisms are still poorly understood. We previously showed that a broad‐host‐range plasmid was poorly maintained in Shewanella oneidensis, but rapidly adapted through mutations in the replication initiation gene trfA1. Here we examined if these mutations reduced the fitness cost of TrfA1, and whether this was due to changes in interaction with the host's DNA helicase DnaB. The strains expressing evolved TrfA1 variants showed a higher growth rate than those expressing ancestral TrfA1. The evolved TrfA1 variants showed a lower affinity to the helicase than ancestral TrfA1 and were no longer able to activate the helicase at the oriV without host DnaA. Moreover, persistence of the ancestral plasmid was increased upon overexpression of DnaB. Finally, the evolved TrfA1 variants generated higher plasmid copy numbers than ancestral TrfA1. The findings suggest that ancestral plasmid instability can at least partly be explained by titration of DnaB by TrfA1. Thus under antibiotic selection resistance plasmids can adapt to a novel bacterial host through partial loss of function mutations that simultaneously increase plasmid copy number and decrease unfavorably high affinity to one of the hosts' essential proteins. The molecular mechanisms by which a broad‐host‐range antibiotic resistance plasmid can adapt to a novel bacterial host and increase its persistence were investigated using experimentally evolved plasmids. These evolved plasmids encode a modified replication initiation protein that simultaneously increases plasmid copy number and decreases interference cost by decreasing binding affinity to the host helicase (DnaB). This in turn causes plasmid replication to be dependent on host DnaA, an example of host specialization.