title: Interspecies signalling: Pseudomonas putida efflux pump TtgGHI is activated by indole to increase antibiotic resistance.
abstract: In Gram-negative bacteria, multidrug efflux pumps are responsible for the extrusion of chemicals that are deleterious for growth. Some of these efflux pumps are induced by endogenously produced effectors, while abiotic or biotic signals induce the expression of other efflux pumps. In Pseudomonas putida, the TtgABC efflux pump is the main antibiotic extrusion system that respond to exogenous antibiotics through the modulation of the expression of this operon mediated by TtgR. The plasmid-encoded TtgGHI efflux pump in P. putida plays a minor role in antibiotic resistance in the parental strain; however, its role is critical in isogenic backgrounds deficient in TtgABC. Expression of ttgGHI is repressed by the TtgV regulator that recognizes indole as an effector, although P. putida does not produce indole itself. Because indole is not produced by Pseudomonas, the indole-dependent antibiotic resistance seems to be part of an antibiotic resistance programme at the community level. Pseudomonas putida recognizes indole added to the medium or produced by Escherichia coli in mixed microbial communities. Transcriptomic analyses revealed that the indole-specific response involves activation of 43 genes and repression of 23 genes. Indole enhances not only the expression of the TtgGHI pump but also a set of genes involved in iron homeostasis, as well as genes for amino acid catabolism. In a ttgABC-deficient P. putida, background ampicillin and other bactericidal compounds lead to cell death. Co-culture of E. coli and P. putida ΔttgABC allowed growth of the P. putida mutant in the presence of ampicillin because of induction of the indole-dependent efflux pump.
authors.affiliation: Consejo Superior de Investigaciones Científicas, Estación Experimental del Zaidín, 18008, Granada, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Molina-Santiago
authors.forename: Abdelali
authors.initials: A
authors.lastname: Daddaoua
authors.forename: Sandy
authors.initials: S
authors.lastname: Fillet
authors.forename: Estrella
authors.initials: E
authors.lastname: Duque
authors.forename: Juan-Luis
authors.initials: JL
authors.lastname: Ramos
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000378:metabolism; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D016958:Pseudomonas putida / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007211:Indoles; D026901:Membrane Transport Proteins; C030374:indole