A GSK J4-Crank Definitely Makes The New GSK J4 Theory So Exciting
  • , 2002), suggesting its possible relationship with other efflux pumps. SmeDEF is involved in both intrinsic and acquired resistance to chloramphenicol, tetracycline and quinolones, as well as acquired resistance to non-antibiotic compounds such as triclosan (Sanchez et al., 2005; Hernandez et al., 2011). S6 Kinase SmeVWX has a role in acquired

    resistance to the same antibiotics (Alonso and Martinez, 2001; Zhang et al., 2001; Chen et al., 2011; Garcia-Leon et al., 2014b). In acquired resistance, the overexpression of the SmeDEF and SmeVWX efflux pumps is related to mutations in the regulators SmeT and SmeRv, respectively (Sanchez et al., 2002; Garcia-Leon et al., 2014b). Other S. maltophilia efflux pumps have recently been studied, including SmeIJK and SmeYZ, which also belong

    to the RND family. Both have a role in intrinsic and acquired resistance, SmeJK to aminoglycosides, tetracycline and ciprofloxacin, and SmeZ to aminoglycosides (Crossman et al., 2008). In addition, their overexpression provides resistance to levofloxacin (Gould et al., 2013). Neither of these efflux pumps has a known associated porin. The efflux pump SmeOP, another RND family member, confers low susceptibility to aminoglycosides, nalidixic acid, doxycycline, macrolides and certain not antibiotic compounds, such as carbonyl cyanide 3-chlorophenylhydrazone (CCCP), crystal violet, sodium dodecyl sulfate (SDS), and tetrachlorosalicylanilide (TCS). In the acquired resistance setting, however, it provides protection only against CCCP and TCS (Lin et al., 2014a). The TolCsm porin has been associated with the SmeOP efflux pump. The tolCsm gene is located upstream of the smeOP operon, in another operon known as smeRo-pcm-tolC. The ��tolCsm phenotype increases susceptibility to several compounds (Huang et al., 2013b), although no correlation is seen with the ��smeOP phenotype. This suggests that the TolCsm porin is not exclusive to the SmeOP efflux pump (Huang et al., 2013b; Lin et al., 2014a). Bioinformatic analyses have also identified two putative MFS-type

    tripartite efflux transporters (Crossman et al., 2008). One of these, emrCABsm, shows high homology with emrAB of E. coli (Lomovskaya and Lewis, 1992). In S. maltophilia, this pump is encoded by an operon of four genes that cover the three efflux pump components and a MarR-type regulator, emrRsm, which is expressed in the same direction. ��emrRsm mutants show low susceptibility to nalidixic acid and CCCP due to the overexpression of the efflux pump, indicating emrRsm to act as a repressor (Huang et al., 2013a). Although ABC-type transporters play a major role in Gram positive bacteria, they have also been found in Gram negative organisms, e.g., MsbA and MacAB in E. coli, VcaM in Vibrio cholerae, MacAB in Neisseria gonorrhoeae, and SmdAB in Serratia marcescens (Lin et al., 2014b). Two ABC efflux pumps, SmrA and MacABCsm, have also been described in S. maltophilia (Al-Hamad et al.

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