title: Homeostasis of glutathione is associated with polyamine-mediated β-lactam susceptibility in Acinetobacter baumannii ATCC 19606.
abstract: Glutathione is a tripeptide (l-γ-glutamyl-l-cysteinyl-glycine) thiol compound existing in many bacteria and maintains a proper cellular redox state, thus protecting cells against toxic substances such as reactive oxygen species. Polyamines (spermine and spermidine) are low-molecular-weight aliphatic polycations ubiquitously presenting in all living cells and modulate many cellular functions. We previously reported that exogenous polyamines significantly enhanced β-lactam susceptibility of β-lactam-associated multidrug-resistant Acinetobacter baumannii. In this study, three genes differentially associated with the polyamine effects on β-lactam susceptibility were identified by transposon mutagenesis of A. baumannii ATCC 19606. All three genes encoded components of membrane transport systems. Inactivation of one of the genes encoding a putative glutathione transport ATP-binding protein increased the accumulation of intracellular glutathione (∼150 to ∼200%) and significantly decreased the polyamine effects on β-lactam susceptibility in A. baumannii ATCC 19606. When the cells were grown with polyamines, the levels of intracellular glutathione in A. baumannii ATCC 19606 significantly decreased from ∼0.5 to ∼0.2 nmol, while the levels of extracellular glutathione were correspondingly increased. However, the levels of total glutathione (intra- plus extracellular) were unchanged when the cells were grown with or without polyamines. Overall, these results suggest that exogenous polyamines induce glutathione export, resulting in decreased levels of intracellular glutathione, which may produce an improper cellular redox state that is associated with the polyamine-mediated β-lactam susceptibility of A. baumannii. This finding may provide a clue for development of new antimicrobial agents and/or novel strategies to treat multidrug-resistant A. baumannii.
authors: Department of Biology, Long Island University, Brooklyn, New York, USA.
authors: Dong H
authors: DH
authors: Kwon
authors: Saboor
authors: S
authors: Hekmaty
authors: Gomattie
authors: G
authors: Seecoomar
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001398:Aztreonam / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002228:Carbenicillin / Q000494:pharmacology; D004251:DNA Transposable Elements; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000235:genetics; D005798:Genes, Bacterial; D005978:Glutathione / Q000378:metabolism*; D006706:Homeostasis; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D016296:Mutagenesis; D010084:Oxidation-Reduction; D013095:Spermidine / Q000494:pharmacology*; D013096:Spermine / Q000494:pharmacology*; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D004251:DNA Transposable Elements; D026901:Membrane Transport Proteins; D047090:beta-Lactams; D013096:Spermine; D001398:Aztreonam; D002228:Carbenicillin; D005978:Glutathione; D013095:Spermidine
references: J Clin Microbiol. 2004 Apr;42(4):1759-63
references: 15071042
references: J Bacteriol. 1986 Dec;168(3):1332-5
references: 2877975
references: Clin Chim Acta. 2004 Jun;344(1-2):23-35
references: 15149868
references: J Bacteriol. 2000 Oct;182(19):5342-50
references: 10986235
references: Infect Immun. 2006 Jan;74(1):352-61
references: 16368990
references: J Bacteriol. 1996 Jan;178(1):54-60
references: 8550442
references: J Biol Chem. 2010 Sep 10;285(37):28698-707
references: 20628056
references: Biochemistry (Mosc). 2005 Nov;70(11):1199-211
references: 16336178
references: J Bacteriol. 2005 Sep;187(17):5861-7
references: 16109926
references: Antioxid Redox Signal. 2006 May-Jun;8(5-6):753-62
references: 16771667
references: Arch Biochem Biophys. 2003 Oct 15;418(2):125-32
references: 14522584
references: Antioxid Redox Signal. 2011 Jul 1;15(1):123-33
references: 20712413
references: Antimicrob Agents Chemother. 2006 May;50(5):1623-7
references: 16641427
references: J Biol Chem. 1988 Nov 25;263(33):17205-8
references: 3053703
references: Cell. 2007 Sep 7;130(5):797-810
references: 17803904
references: Genes Dev. 2007 Mar 1;21(5):601-14
references: 17344419
references: Methods Enzymol. 1981;77:373-82
references: 7329314
references: J Bacteriol. 2003 Mar;185(6):1942-50
references: 12618458
references: Antioxid Redox Signal. 2011 Mar 15;14(6):1049-63
references: 20626317
references: Clin Microbiol Rev. 2008 Jul;21(3):538-82
references: 18625687
references: J Bacteriol. 1986 Oct;168(1):109-14
references: 3531162
references: Antimicrob Agents Chemother. 2006 May;50(5):1615-22
references: 16641426
references: Int J Antimicrob Agents. 2008 Aug;32(2):106-19
references: 18571905
references: Antimicrob Agents Chemother. 2007 Jun;51(6):2070-7
references: 17438056
references: Annu Rev Biochem. 1983;52:711-60
references: 6137189
references: J Bacteriol. 1978 Mar;133(3):1126-9
references: 417060
references: Antimicrob Agents Chemother. 2009 Dec;53(12):5150-4
references: 19752280
references: Biochim Biophys Acta. 2013 May;1830(5):3182-98
references: 23075826
references: Int J Antimicrob Agents. 2013 Jan;41(1):70-4
references: 23148986
references: J Bacteriol. 2006 Nov;188(22):7830-9
references: 16980463
references: Amino Acids. 2004 Dec;27(3-4):347-58
references: 15592759
references: Mol Aspects Med. 2009 Feb-Apr;30(1-2):42-59
references: 18601945
references: Appl Environ Microbiol. 1996 Sep;62(9):3094-100
references: 8795195
references: Future Microbiol. 2008 Dec;3(6):649-60
references: 19072182
references: J Biochem. 2006 Jan;139(1):11-6
references: 16428314
references: Nat Rev Microbiol. 2007 Dec;5(12):939-51
references: 18007677
references: J Bacteriol. 1993 Sep;175(18):6038-40
references: 8104180
references: J Bacteriol. 2006 Apr;188(7):2355-63
references: 16547021