Index no: EP1797
Evolution of high-level resistance during low-level antibiotic exposure
Antibiotics are used to treat infections in all living beings including their growth promotion and finally will end up in the environment. However antibiotic concentrations below the minimal inhibitory concentration (MIC) may be present in the some animal body compartments and tissues during the use of therapeutic promotion as well as bacteria are exposed for long time to low concentration of polluting antibiotics, present in various environments. Bacteria will stop growing when exposing to antibiotic concentrations above MIC and they will maintain their growth when resistance mutations present prior to antibiotic exposure. Thus bacteria can grow at sub-MIC of antibiotics during lethal selection. They can also generate various trajectories of evolution that have different potentials with progressive increment of resistance mutations which is often linked to a severe reduction in bacteria growth rate. It was investigated that the evolution and the genetics of antibiotics resistance by a bacteria pathogen, called ‘salmonella’ during long term exposure to streptomycin at low sub-MIC levels. This was done via three different novel mechanisms: alteration of the ribosomal RNA mutations, decrement in aminoglycoside uptake and induction of the aminoglycoside- modifying enzyme AadA. Finally it could be found that when wild-type bacteria are exposure to constant low levels of antibiotics, they evolved five causative high-level resistance mutations (gidB, trkH, nuoG, cyoB, znuA ) which had individually small effects through stepwise accumulation and when mutations are combined, they showed high resistance because of the strong positive epistasis. So it is clear about low MIC levels of antibiotics are bacteria resistant. ( words of the paragraph :254 )
Anderson, D.I. & Hughes, D. Microbiological effects of sublethal levels of antibiotics. Nat. Rev. Microbiol. 12, 456-478 (2014).
Gullberg , E. et al. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 7, e1002158 (2011).
https://uu.diva-portal.org/smash/get/diva2:759386/FULLTEXT01.pdf(2018/05/07 6.00p.m to 9.00p.m)