title: A quorum sensing small volatile molecule promotes antibiotic tolerance in bacteria.
abstract: Bacteria can be refractory to antibiotics due to a sub-population of dormant cells, called persisters that are highly tolerant to antibiotic exposure. The low frequency and transience of the antibiotic tolerant "persister" trait has complicated elucidation of the mechanism that controls antibiotic tolerance. In this study, we show that 2' Amino-acetophenone (2-AA), a poorly studied but diagnostically important small, volatile molecule produced by the recalcitrant gram-negative human pathogen Pseudomonas aeruginosa, promotes antibiotic tolerance in response to quorum-sensing (QS) signaling. Our results show that 2-AA mediated persister cell accumulation occurs via alteration of the expression of genes involved in the translational capacity of the cell, including almost all ribosomal protein genes and other translation-related factors. That 2-AA promotes persisters formation also in other emerging multi-drug resistant pathogens, including the non 2-AA producer Acinetobacter baumannii implies that 2-AA may play an important role in the ability of gram-negative bacteria to tolerate antibiotic treatments in polymicrobial infections. Given that the synthesis, excretion and uptake of QS small molecules is a common hallmark of prokaryotes, together with the fact that the translational machinery is highly conserved, we posit that modulation of the translational capacity of the cell via QS molecules, may be a general, widely distributed mechanism that promotes antibiotic tolerance among prokaryotes.
authors.affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America ; Shriners Hospitals for Children Boston, Boston, Massachusetts, United States of America.
authors.forename: Yok-Ai
authors.initials: YA
authors.lastname: Que
authors.affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America ; Shriners Hospitals for Children Boston, Boston, Massachusetts, United States of America ; IYAR, The Israeli Institute for Advanced Research, Israel ; Institute of Dental Sciences and School of Dental Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Ronen
authors.initials: R
authors.lastname: Hazan
authors.affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America ; Shriners Hospitals for Children Boston, Boston, Massachusetts, United States of America.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Strobel
authors.affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America ; Shriners Hospitals for Children Boston, Boston, Massachusetts, United States of America.
authors.forename: Damien
authors.initials: D
authors.lastname: Maura
authors.affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America ; Shriners Hospitals for Children Boston, Boston, Massachusetts, United States of America.
authors.forename: Jianxin
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America ; Shriners Hospitals for Children Boston, Boston, Massachusetts, United States of America.
authors.forename: Meenu
authors.initials: M
authors.lastname: Kesarwani
authors.affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America ; Shriners Hospitals for Children Boston, Boston, Massachusetts, United States of America.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Panopoulos
authors.affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America ; Shriners Hospitals for Children Boston, Boston, Massachusetts, United States of America.
authors.forename: Amy
authors.initials: A
authors.lastname: Tsurumi
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Marlyse
authors.initials: M
authors.lastname: Giddey
authors.affiliation: Stanford Genome Technology Center, Stanford University, Palo Alto, California, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Wilhelmy
authors.affiliation: Stanford Genome Technology Center, Stanford University, Palo Alto, California, United States of America.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Mindrinos
authors.affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America ; Shriners Hospitals for Children Boston, Boston, Massachusetts, United States of America.
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Rahme
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism; D053038:Quorum Sensing / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents