Campylobacter capsule and lipooligosaccharide confer resistance to serum and cationic antimicrobials.
The innate immune system plays a critical role in host defense against mucosal bacteria. Campylobacter jejuni is a major cause of human gastroenteritis that usually resolves spontaneously within several days, suggesting that innate mechanisms are important to control the infection. However, the specific means by which this occurs is not well understood. While diarrheal isolates of C. jejuni usually are susceptible to human serum, we found that a systemic strain of C. jejuni, isolated from the cerebrospinal fluid of an infant with meningitis, is relatively more resistant to human serum, the Bactericidal/Permeability-Increasing Protein (BPI), an endogenous cationic antimicrobial protein, and the cationic peptide antibiotic polymyxin B. To test the hypothesis that the surface properties of this strain contributed to its ability to withstand these innate host defenses, we constructed isogenic mutants in capsule (kpsM) and lipooligosaccharide (waaF) and complemented these mutants by insertion of the complementation construct in trans into hipO, a chromosomal locus. We found that capsule expression was essential for serum resistance, whereas lipooligosaccharide played no substantial role. In contrast, the lipooligosaccharide mutant showed increased sensitivity to polymyxin B, α-defensins, cathelicidins, and BPI. These findings suggest that the polysaccharides of C. jejuni strains contribute differently to resistance against host innate immunity; whereby capsule is more important for resisting human complement and lipooligosaccharide is more important for protection against killing mediated by cationic antimicrobial peptides and proteins.
Department of Microbiology, New York University School of Medicine, NY, USA.
Thormika
T
Keo
Jennifer
J
Collins
Pratima
P
Kunwar
Martin J
MJ
Blaser
Nicole M
NM
Iovine
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D016667:Bacterial Capsules / Q000235:genetics / Q000276:immunology*; D001770:Blood Bactericidal Activity; D002169:Campylobacter Infections / Q000276:immunology* / Q000382:microbiology; D016123:Campylobacter jejuni / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D024881:Drug Resistance, Bacterial; D006801:Humans; D008070:Lipopolysaccharides / Q000235:genetics / Q000276:immunology*; D044967:Serum / Q000276:immunology
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides
Nature. 2000 Feb 10;403(6770):665-8
10688204
J Biol Chem. 2006 Feb 3;281(5):2858-67
16326712
C R Biol. 2004 Jun;327(6):539-49
15330253
J Infect Dis. 1985 Feb;151(2):227-35
3968449
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10973-8
9380744
Springer Semin Immunopathol. 1994;15(4):327-44
8153871
Mol Microbiol. 1997 Mar;23(5):1021-31
9076738
J Bacteriol. 2002 Apr;184(8):2100-7
11914340
J Biol Chem. 2007 Sep 28;282(39):28566-28576
17675288
Appl Environ Microbiol. 1988 Oct;54(10):2365-70
3060015
J Bacteriol. 1995 May;177(9):2396-402
7730270
Lancet. 1994 Aug 13;344(8920):429-31
7520106
Trends Microbiol. 2008 Sep;16(9):428-35
18707886
J Infect Dis. 1986 Mar;153(3):552-9
3512731
Bioinformatics. 2007 Nov 1;23(21):2947-8
17846036
J Biol Chem. 2002 Jan 4;277(1):327-37
11689567
Infect Immun. 2002 Feb;70(2):787-93
11796612
Nature. 2003 Apr 3;422(6931):522-6
12660734
J Bacteriol. 1987 Nov;169(11):5320-3
2822671
J Infect Dis. 1986 Sep;154(3):497-503
3525697
Mol Microbiol. 2001 May;40(3):769-77
11359581
Pediatr Clin North Am. 2000 Dec;47(6):1339-54
11130999
Gene. 1993 Sep 30;132(1):131-5
8406035
J Bacteriol. 2010 Apr;192(8):2182-92
20139192
Immunochemistry. 1976 Oct;13(10):813-8
187544
J Rheumatol. 2003 Aug;30(8):1719-24
12913926
Curr Opin Gastroenterol. 2004 Mar;20(2):82-8
15703626
Curr Opin Gastroenterol. 2007 Mar;23(2):115-20
17268238
Eur J Biochem. 2002 Nov;269(21):5119-36
12392544
Infect Immun. 2000 Dec;68(12):6656-62
11083778
FEBS J. 2006 Sep;273(17):3975-89
16879613
J Bacteriol. 1996 Jun;178(11):3335-8
8655516
J Clin Invest. 1995 Apr;95(4):1916-24
7706499
Infect Immun. 2008 Mar;76(3):986-93
18174337
J Bacteriol. 2008 Aug;190(16):5681-9
18556784
J Bacteriol. 1992 Sep;174(18):5916-22
1522068
Infect Immun. 1992 Nov;60(11):4754-61
1398985
J Biol Chem. 2000 Feb 11;275(6):3896-906
10660542
J Bacteriol. 2008 Mar;190(5):1568-74
18156268
MMWR Morb Mortal Wkly Rep. 2010 Apr 16;59(14):418-22
20395935
Infect Immun. 2005 Nov;73(11):7281-9
16239524
Biochem Soc Trans. 2003 Aug;31(Pt 4):785-90
12887306
J Clin Invest. 1980 Mar;65(3):619-28
6986410
Mol Microbiol. 2000 Feb;35(3):529-41
10672176
N Engl J Med. 2000 Dec 7;343(23):1703-14
11106721
Trends Microbiol. 2000 Sep;8(9):402-10
10989307
Microbiology (Reading). 2004 Jun;150(Pt 6):1957-1964
15184581
J Clin Microbiol. 2001 Jan;39(1):279-84
11136784
Nucleic Acids Res. 2002 Jun 1;30(11):2444-52
12034832
Infect Immun. 1984 May;44(2):292-8
6715034
Clin Microbiol Infect. 2004 Oct;10(10):868-76
15373879
FEBS Lett. 1995 Jul 10;368(1):173-6
7615076
Proc Natl Acad Sci U S A. 1988 Feb;85(3):856-60
3277182
FEBS Lett. 1995 Oct 23;374(1):1-5
7589491
Crit Rev Immunol. 2000;20(5):407-31
11145218
Br Med J. 1977 Jul 2;2(6078):9-11
871765
J Bacteriol. 2009 Jun;191(12):3861-8
19376861
Lett Appl Microbiol. 1997 Oct;25(4):274-8
9424104
Appl Environ Microbiol. 2005 Jul;71(7):4004-13
16000815
J Biol Chem. 1978 Apr 25;253(8):2664-72
344320
Infect Immun. 1986 Feb;51(2):594-9
3510983
Ann Intern Med. 1984 Jun;100(6):832-4
6721298
Nat Rev Microbiol. 2004 Sep;2(9):727-38
15372083
Infect Immun. 2004 Apr;72(4):2452-5
15039381
Am J Physiol. 1999 Aug;277(2):G257-61
10444437
J Infect Dis. 1985 Sep;152(3):592-6
4031557
J Clin Invest. 1992 Sep;90(3):1122-30
1522221
Nat Immunol. 2000 Aug;1(2):113-8
11248802
J Immunol. 2005 Apr 15;174(8):4901-7
15814717
J Clin Microbiol. 1993 Aug;31(8):1971-4
8370723