title: Killing of Staphylococcus aureus in murine macrophages by chloroquine used alone and in combination with ciprofloxacin or azithromycin.
abstract: This study aimed to determine any alteration in the killing of Staphylococcus aureus in murine peritoneal macrophages when chloroquine (CQ) is used alone compared with when it is used in combination with ciprofloxacin (CIP) or azithromycin (AZM). The study also aimed to find out the implication of reactive oxygen species (ROS) production and cytokine release in the intracellular killing of S. aureus in macrophages. We present here data obtained with a model of S. aureus-infected mouse peritoneal macrophages in which the intracellular growth of the bacteria and the influence of antibiotics was monitored for 30, 60, and 90 minutes in the presence or absence of CQ along with the production of ROS and alteration in levels of antioxidant enzymes and cytokines. It was observed that S. aureus-triggered cytokine response was regulated when macrophages were co-cultured with CQ and AZM as compared with CQ stimulation only. It can be suggested that action of AZM in mediating bacterial killing is enhanced by the presence of CQ, indicating enhanced uptake of AZM during early infection that may be essential for bacteria killing by AZM. Reduction of oxidative stress burden on the S. aureus-infected macrophages may pave the way for better killing of internalized S. aureus by CQ plus ciprofloxacin (CIP) or CQ plus AZM. Based on these observations, one may speculate that in an inflammatory milieu, CQ loaded with AZM elicits a stronger proinflammatory response by increasing the intracellular uptake of AZM or CIP, thus enabling the immune system to mount a more robust and prolonged response against intracellular pathogens.
authors: Department of Physiology, Immunology laboratory, University of Calcutta, University Colleges of Science and Technology, Calcutta, India.
authors: Somrita
authors: S
authors: Dey
authors: Department of Physiology, Immunology laboratory, University of Calcutta, University Colleges of Science and Technology, Calcutta, India.
authors: Biswadev
authors: B
authors: Bishayi
keywords: azithromycin; ciprofloxacin; intracellular survival
references: J Infect Dis. 1994 Feb;169(2):330-6
references: 8106766
references: J Immunol. 2000 Apr 1;164(7):3713-22
references: 10725730
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: Immunity. 2010 Mar 26;32(3):305-15
references: 20346772
references: Microb Pathog. 1995 Dec;19(6):409-19
references: 8852281
references: Pharmacol Toxicol. 1999 Oct;85(4):188-91
references: 10563518
references: Trends Microbiol. 2000 Aug;8(8):341-3
references: 10920387
references: Int J Antimicrob Agents. 2003 Dec;22(6):579-87
references: 14659655
references: Int J Tissue React. 1994;16(5-6):211-20
references: 7558665
references: Inflammation. 2015 Apr;38(2):812-27
references: 25129059
references: Rev Infect Dis. 1989 Mar-Apr;11(2):213-45
references: 2649959
references: Nat Rev Rheumatol. 2012 Sep;8(9):522-33
references: 22801982
references: Microb Pathog. 2003 Oct;35(4):159-68
references: 12946328
references: Br Med Bull. 1993 Jul;49(3):481-93
references: 8221017
references: Infect Immun. 1999 Feb;67(2):885-90
references: 9916104
references: Am Fam Physician. 2002 Feb 1;65(3):455-64
references: 11858629
references: Scand J Immunol. 2012 Dec;76(6):528-40
references: 22924656
references: Pharmacol Res. 2011 Sep;64(3):298-307
references: 21473915
references: PLoS One. 2008 Jul 02;3(7):e2587
references: 18596975
references: Eur Respir J. 2009 Jan;33(1):171-81
references: 19118228
references: Eur J Clin Microbiol Infect Dis. 1991 Feb;10(2):100-6
references: 1864271
references: J Antimicrob Chemother. 2004 Feb;53(2):167-73
references: 14729736
references: Semin Arthritis Rheum. 1993 Oct;23(2 Suppl 1):82-91
references: 8278823
references: J Immunol Res. 2014;2014:613136
references: 25136646
references: Proc Natl Acad Sci U S A. 1978 Jul;75(7):3327-31
references: 28524
references: J Clin Invest. 1997 Sep 15;100(6):1640-6
references: 9294133
references: Am J Ther. 2006 Sep-Oct;13(5):432-5
references: 16988539
references: J Antimicrob Chemother. 1998 Jun;41(6):655-8
references: 9687105
references: Scand J Immunol. 2014 Aug;80(2):127-43
references: 24846691
references: Ann Rheum Dis. 1999 Nov;58 Suppl 1:I32-9
references: 10577971
references: J Antimicrob Chemother. 1990 Oct;26 Suppl B:27-39
references: 2258352
references: J Vasc Res. 2002 May-Jun;39(3):191-207
references: 12097818
references: J Antimicrob Chemother. 2006 May;57(5):883-90
references: 16533826
references: Am J Physiol Renal Physiol. 2008 May;294(5):F1050-8
references: 18305095
references: Antimicrob Agents Chemother. 1987 Apr;31(4):660-2
references: 3606071
references: J Immunol. 2011 Apr 15;186(8):4794-804
references: 21398612
references: Cell Immunol. 2012 Sep;279(1):78-86
references: 23099154
references: Mediators Inflamm. 2013;2013:165974
references: 23853427
references: Antimicrob Agents Chemother. 1999 Oct;43(10):2457-62
references: 10508024
references: Chemotherapy. 1993 Nov-Dec;39(6):424-31
references: 8222871
references: Inflamm Res. 2013 Mar;62(3):259-73
references: 23229721
references: N Engl J Med. 1998 Aug 20;339(8):520-32
references: 9709046
references: Int Immunol. 2002 Feb;14(2):201-12
references: 11809739
references: J Immunol. 1997 May 15;158(10):4901-7
references: 9144507
references: Immunobiology. 2010 Jun;215(6):443-51
references: 19773091
references: Antimicrob Agents Chemother. 1987 Oct;31(10):1553-7
references: 3481246
references: Nat Rev Immunol. 2012 Jun 15;12(7):492-502
references: 22699831
references: Methods Enzymol. 1986;132:95-180
references: 3821529
references: J Immunol. 1999 Sep 1;163(5):2909-15
references: 10453038
references: J Clin Invest. 1994 Apr;93(4):1422-9
references: 8163646
references: Anal Biochem. 1968 Oct 24;25(1):192-205
references: 4973948
references: Braz J Med Biol Res. 2014 May;47(5):355-60
references: 24760117
references: Infect Immun. 1998 Dec;66(12):5994-8
references: 9826383
references: Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S350-9
references: 18462090
references: J Cell Biol. 1981 Sep;90(3):665-9
references: 6169733
references: PLoS One. 2013 Jun 14;8(6):e65913
references: 23799062
references: Indian J Med Res. 2008 Apr;127(4):305-16
references: 18577785
references: Nat Genet. 1995 Feb;9(2):202-9
references: 7719350
references: Antimicrob Agents Chemother. 2003 Jul;47(7):2283-92
references: 12821480
references: J Antimicrob Chemother. 2005 Apr;55(4):511-7
references: 15731197
references: BMC Microbiol. 2014 Jul 25;14:207
references: 25059520
references: Curr Protoc Immunol. 2008 Nov;Chapter 14:14.2.1-14.2.8
references: 19016446
references: Indian J Microbiol. 2010 Oct;50(4):375-84
references: 22282603
references: Am J Physiol Cell Physiol. 2003 Nov;285(5):C1339-47
references: 12878488
references: Br J Pharmacol. 2012 Mar;165(5):1348-60
references: 21726210
references: Anal Biochem. 1998 Jan 1;255(1):127-32
references: 9448851
references: Eur J Immunol. 2004 Sep;34(9):2541-50
references: 15307186
references: J Biol Chem. 2013 Mar 1;288(9):6417-26
references: 23322784
references: Microb Pathog. 2009 Aug;47(2):57-67
references: 19439176
references: Lab Invest. 1975 Nov;33(5):469-77
references: 1186128
references: Antimicrob Agents Chemother. 2000 Mar;44(3):511-21
references: 10681311
references: J Infect Dis. 1991 Oct;164(4):830
references: 1894954
references: Lancet Infect Dis. 2005 May;5(5):275-86
references: 15854883
references: J Immunol. 2000 Aug 1;165(3):1534-40
references: 10903761
references: Inflamm Res. 2008 Jul;57(7):340-9
references: 18607538
references: J Exp Med. 2003 May 19;197(10):1323-34
references: 12756268
references: Clin Microbiol Rev. 2010 Jul;23(3):590-615
references: 20610825
references: Int J Antimicrob Agents. 2001 Nov;18(5):419-25
references: 11711255
references: Eur J Clin Pharmacol. 1992;42(4):429-33
references: 1307690
references: Indian J Exp Biol. 2012 Oct;50(10):677-89
references: 23214260
references: J Exp Med. 1952 Feb;95(2):209-30
references: 14907971
references: J Pharmacol Exp Ther. 1999 Aug;290(2):863-70
references: 10411603
references: Arthritis Res Ther. 2012 Jun 27;14(3):R155
references: 22734582
references: Nat Rev Microbiol. 2005 Dec;3(12):948-58
references: 16322743
references: Infect Dis Clin North Am. 2003 Sep;17(3):615-34
references: 14711080
references: J Cell Biol. 1981 Jun;89(3):645-52
references: 6166620
references: Microbes Infect. 2003 Jun;5(7):621-7
references: 12787738
references: Eur J Clin Microbiol Infect Dis. 1991 Feb;10(2):114-8
references: 1864273
references: Ecotoxicol Environ Saf. 2011 Feb;74(2):166-73
references: 20554323
references: Int J Antimicrob Agents. 2002 Apr;19(4):261-8
references: 11978497
references: Ann Trop Med Parasitol. 2006 Oct;100(7):579-84
references: 16989683
references: Lancet Infect Dis. 2001 Oct;1(3):147-55
references: 11871491
references: Lupus. 1996 Jun;5 Suppl 1:S11-5
references: 8803904
references: Infect Immun. 1998 Jan;66(1):336-42
references: 9423876
references: Eur J Clin Microbiol Infect Dis. 1991 Oct;10(10):821-7
references: 1662625
references: Aliment Pharmacol Ther. 2000 Jun;14(6):801-6
references: 10848665