Mutation rate plasticity in rifampicin resistance depends on Escherichia coli cell-cell interactions.
Variation of mutation rate at a particular site in a particular genotype, in other words mutation rate plasticity (MRP), can be caused by stress or ageing. However, mutation rate control by other factors is less well characterized. Here we show that in wild-type Escherichia coli (K-12 and B strains), the mutation rate to rifampicin resistance is plastic and inversely related to population density: lowering density can increase mutation rates at least threefold. This MRP is genetically switchable, dependent on the quorum-sensing gene luxS--specifically its role in the activated methyl cycle--and is socially mediated via cell-cell interactions. Although we identify an inverse association of mutation rate with fitness under some circumstances, we find no functional link with stress-induced mutagenesis. Our experimental manipulation of mutation rates via the social environment raises the possibility that such manipulation occurs in nature and could be exploited medically.
Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Manchester M13 9PT, UK.
Rok
R
Krašovec
School of Science and Technology, Middlesex University, London NW4 4BT, UK.
Roman V
RV
Belavkin
1] Statistical Laboratory, DPMMS, University of Cambridge, Cambridge CB3 0WB, UK [2] Department of Statistics, University of Warwick, Warwick CV4 7AL, UK.
John A D
JA
Aston
Research Institute for the Environment, Physical Sciences and Applied Mathematics, Keele University, Keele ST5 5BG, UK.
Alastair
A
Channon
Research Institute for the Environment, Physical Sciences and Applied Mathematics, Keele University, Keele ST5 5BG, UK.
Elizabeth
E
Aston
Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Manchester M13 9PT, UK.
Bharat M
BM
Rash
1] Wolfson Molecular Imaging Centre, The University of Manchester, Manchester M20 3LJ, UK [2] Manchester Pharmacy School, The University of Manchester, Manchester M13 9PT, UK.
Manikandan
M
Kadirvel
Manchester Pharmacy School, The University of Manchester, Manchester M13 9PT, UK.
Sarah
S
Forbes
Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Manchester M13 9PT, UK.
Christopher G
CG
Knight
D000704:Analysis of Variance; D001426:Bacterial Proteins / Q000378:metabolism; D013437:Carbon-Sulfur Lyases / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D056084:Genetic Fitness / Q000235:genetics; D014644:Genetic Variation; D056265:Microbial Interactions / Q000502:physiology*; D059645:Mutation Rate; D011156:Population Density; D060888:Real-Time Polymerase Chain Reaction; D012293:Rifampin
D001426:Bacterial Proteins; D017931:DNA Primers; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria; D012293:Rifampin