A REGULATORY CASCADE INVOLVING AARG, A PUTATIVE SENSOR KINASE, CONTROLS THE EXPRESSION OF THE 2'-N-ACETYLTRANSFERASE AND AN INTRINSIC MULTIPLE ANTIBIOTIC-RESISTANCE (MAR) RESPONSE IN PROVIDENCIA-STUARTII
Pn. Rather et al., A REGULATORY CASCADE INVOLVING AARG, A PUTATIVE SENSOR KINASE, CONTROLS THE EXPRESSION OF THE 2'-N-ACETYLTRANSFERASE AND AN INTRINSIC MULTIPLE ANTIBIOTIC-RESISTANCE (MAR) RESPONSE IN PROVIDENCIA-STUARTII, Molecular microbiology, 28(6), 1998, pp. 1345-1353
A recessive mutation, aarG1, has been identified that resulted in an 1
8-fold increase in the expression of beta-galactosidase from an aac(2'
)-lacZ fusion, Transcriptional fusions and Northern blot analysis demo
nstrated that the aarG1 allele also resulted in a large increase in th
e expression of aarP, a gene encoding a transcriptional activator of a
ac(2')-la, The effects of aarG1 on aac(2')-la expression were mediated
by aarP-dependent and -independent mechanisms. The aarG1 allele also
resulted in a multiple antibiotic resistance (Mar) phenotype, which in
cluded increased chloramphenicol, tetracycline and fluoroquinolone res
istance, This Mar phenotype also resulted from aarP-dependent and -ind
ependent mechanisms. Sequence analysis of the aarG locus revealed the
presence of two open reading frames, designated aarRand aarG, organize
d in tandem, The putative AarR protein displayed 75% amino acid identi
ty to the response regulator PhoP, and the AarG protein displayed 57%
amino acid identity to the sensor kinase PhoQ, The aarG1 mutation, a C
to T substitution, resulted in a threonine to isoleucine substitution
at position 279 (T279I) in the putative sensor kinase, The AarG produ
ct was functionally similar to PhoQ, as it was able to restore wild-ty
pe levels of maganin resistance to a Salmonella typhimurium phoQ mutan
t, However, expression of the aarP and aac(2')-la genes was not signif
icantly affected by the levels of Mg2+ or Ca2+, suggesting that aarG s
enses a signal other than divalent cations.