Aminoglycoside Phosphotransferase AphSR2 from Streptomyces rimosus ATCC 10970: Dependence of Antibiotic Resistance on Serine-Threonine Protein Kinases PkSR1 and PkSR2

Streptomyces rimosus ATCC 10970 contains 14 genes annotated as aminoglycoside phosphotransferases in its genome: aphSR1 – aphSR14 . We have previously shown that the aphVIII ( aphSR5 ) and aph ( 3'' ) -Id ( aphSR3 ) genes, when cloning in E. coli , cause resistance to kanamycin, neomycin, paromomycin, and streptomycin. It was found for Aph(3')-VIII that antibiotic resistance increased after phosphorylation at the Ser146 motif in the active site of the enzyme by serine-threonine protein kinases (STPKs). The aphSR2 gene, when cloning in E. coli , causes resistance to neomycin and hygromycin. In this work, in order to assess the possibility of influence of STPK genes on increasing resistance to aminoglycoside antibiotics, we performed a combined cloning into E. coli at pET32a of the aphSR2 gene and the STPK genes ( pkSR1 and pkSR2 ) localized in one cluster of the S. rimosus ATCC 10970 genome. We detected that, in the construction E. coli/aphSR2/pkSR1 , there is a 2-fold increase in resistance to neomycin. The presented data are the second example of the STPK effect on the modulation of the level of resistance to aminoglycoside antibiotics in bacteria of the genus Streptomyces .