title: The carbon source influences the efflux pump-mediated antimicrobial resistance in clinically important Gram-negative bacteria.
abstract: OBJECTIVE
  Multidrug efflux pumps are proteins known to play an important role in resistance in bacteria. These proteins are located in the inner membrane (IM), together with many other proteins, including inducible permeases that participate in the uptake of non-phosphotransferase system (PTS) carbohydrates (i.e. carbohydrates uptaken by mechanisms other than the PTS). However, lipid bilayer space in the IM is limited. Therefore, we examined whether the overexpression of unrelated IM proteins is able to interfere with the efflux-mediated resistance mechanism, consequently increasing the susceptibility towards different antimicrobial compounds.
  
  
  METHODS
  We cultured bacteria under different conditions that increase the synthesis of unrelated IM proteins, either by using a non-PTS carbohydrate as the sole carbon source or by artificially overexpressing IM proteins, prior to determining the resistance to different antimicrobial compounds by disc diffusion assays.
  
  
  RESULTS
  We observed that efflux-pump-mediated resistance is affected by the carbon source in all the strains tested, exhibiting increased susceptibility when a non-PTS carbohydrate was used as the sole carbon source. Moreover, when we artificially overexpressed an unrelated IM protein, we also observed decreased efflux-mediated resistance.
  
  
  CONCLUSIONS
  These results strongly suggest that overexpression of IM proteins, by using a non-PTS carbohydrate as the sole carbon source, or by artificially introducing a high number of copies of an unrelated IM protein, competes with the antibiotic efflux systems, thereby decreasing the efflux-mediated resistance to different antimicrobial compounds. This sort of competition arises because of the limited available space in the bacterial IM, or by an unknown mechanism.
authors.affiliation: Laboratorio de Microbiología, Facultad de Ciencias Biológicas,  Universidad Andres Bello, Santiago,  Chile.
authors.forename: Nicolás A
authors.initials: NA
authors.lastname: Villagra
authors.forename: Juan A
authors.initials: JA
authors.lastname: Fuentes
authors.forename: Matías R
authors.initials: MR
authors.lastname: Jofré
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Hidalgo
authors.forename: Patricia
authors.initials: P
authors.lastname: García
authors.forename: Guido C
authors.initials: GC
authors.lastname: Mora
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology*; D001693:Biological Transport, Active; D002244:Carbon / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry; D024901:Drug Resistance, Multiple, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D002244:Carbon