Indirect pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in polymicrobial otitis media occurs via interspecies quorum signaling.
Otitis media (OM) is among the leading diseases of childhood and is caused by opportunists that reside within the nasopharynx, such as Haemophilus influenzae and Moraxella catarrhalis. As with most airway infections, it is now clear that OM infections involve multiple organisms. This study addresses the hypothesis that polymicrobial infection alters the course, severity, and/or treatability of OM disease. The results clearly show that coinfection with H. influenzae and M. catarrhalis promotes the increased resistance of biofilms to antibiotics and host clearance. Using H. influenzae mutants with known biofilm defects, these phenotypes were shown to relate to biofilm maturation and autoinducer-2 (AI-2) quorum signaling. In support of the latter mechanism, chemically synthesized AI-2 (dihydroxypentanedione [DPD]) promoted increased M. catarrhalis biofilm formation and resistance to antibiotics. In the chinchilla infection model of OM, polymicrobial infection promoted M. catarrhalis persistence beyond the levels seen in animals infected with M. catarrhalis alone. Notably, no such enhancement of M. catarrhalis persistence was observed in animals infected with M. catarrhalis and a quorum signaling-deficient H. influenzae luxS mutant strain. We thus conclude that H. influenzae promotes M. catarrhalis persistence within polymicrobial biofilms via interspecies quorum signaling. AI-2 may therefore represent an ideal target for disruption of chronic polymicrobial infections. Moreover, these results strongly imply that successful vaccination against the unencapsulated H. influenzae strains that cause airway infections may also significantly impact chronic M. catarrhalis disease by removing a reservoir of the AI-2 signal that promotes M. catarrhalis persistence within biofilm.
Armbruster
Chelsie E
CE
Department of Microbiology and Immunology, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA.
Hong
Wenzhou
W
Pang
Bing
B
Weimer
Kristin E D
KE
Juneau
Richard A
RA
Turner
James
J
Swords
W Edward
WE
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D018441:Biofilms / Q000187:drug effects; D002682:Chinchilla; D024881:Drug Resistance, Bacterial; D006192:Haemophilus Infections / Q000188:drug therapy / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D001936:Moraxella catarrhalis / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D045828:Moraxellaceae Infections / Q000188:drug therapy / Q000382:microbiology*; D010033:Otitis Media / Q000188:drug therapy / Q000382:microbiology*; D053038:Quorum Sensing / Q000187:drug effects
D000900:Anti-Bacterial Agents
Clin Infect Dis. 2009 Dec 1;49(11):1641-7
19886799
Infect Immun. 2006 Mar;74(3):1828-36
16495557
Infect Immun. 1988 Feb;56(2):331-5
2892792
Annu Rev Biomed Eng. 2008;10:145-67
18647113
Mol Microbiol. 2003 Dec;50(5):1477-91
14651632
J Clin Microbiol. 1999 Jun;37(6):1771-6
10325322
Science. 1999 May 21;284(5418):1318-22
10334980
Drugs. 1986;31 Suppl 3:93-6
3732085
Pediatrics. 2004 May;113(5):1451-65
15121972
Infect Immun. 1996 Sep;64(9):3920-4
8751951
Nat Rev Microbiol. 2008 Aug;6(8):635-43
18536728
Am J Otolaryngol. 1996 Mar-Apr;17(2):106-11
8820185
Int J Med Microbiol. 2002 Jul;292(2):107-13
12195733
JAMA. 2006 Jul 12;296(2):202-11
16835426
Infect Immun. 2005 Jun;73(6):3210-8
15908345
Am J Respir Crit Care Med. 2006 Jul 15;174(2):213-20
16675778
Int J Pediatr Otorhinolaryngol. 2008 Apr;72(4):491-9
18272237
J Biol Chem. 2002 Apr 26;277(17):14598-611
11842084
Mol Microbiol. 1994 Jul;13(2):273-86
7984107
Mol Microbiol. 1996 Dec;22(5):951-65
8971716
Antimicrob Agents Chemother. 2004 Mar;48(3):890-6
14982780
Mol Microbiol. 2006 Jun;60(6):1446-56
16796680
J Bacteriol. 2007 Aug;189(15):5559-65
17526716
Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1639-44
9990077
Infect Immun. 2009 Sep;77(9):4081-91
19564381
Curr Top Microbiol Immunol. 2008;322:85-105
18453273
Infect Immun. 2006 Jul;74(7):4021-9
16790775
Pediatrics. 1997 Mar;99(3):318-33
9041282
Cell Microbiol. 2002 Apr;4(4):191-200
11952636
Curr Opin Otolaryngol Head Neck Surg. 2007 Oct;15(5):347-51
17823552
Pediatrics. 2001 Jul;108(1):1-7
11433046
Annu Rev Cell Dev Biol. 2005;21:319-46
16212498
J Bacteriol. 2007 Nov;189(22):8300-7
17573475
Science. 1998 Apr 10;280(5361):295-8
9535661
Antimicrob Agents Chemother. 1998 Oct;42(10):2521-6
9756750
J Clin Microbiol. 1997 Nov;35(11):2854-8
9350746
Vaccine. 2000 Dec 8;19 Suppl 1:S2-8
11163456
Pediatr Infect Dis J. 2007 Oct;26(10 Suppl):S17-9
18049376
Infect Immun. 2007 Sep;75(9):4211-8
17591788
J Antimicrob Chemother. 1980 May;6(3):307-9
6967479
Lancet. 1969 Apr 19;1(7599):793-5
4180358
J Bacteriol. 2005 Jan;187(1):238-48
15601708
Infect Immun. 2007 Feb;75(2):958-65
17130253
Drugs. 1986;31 Suppl 3:97-102
3488202
Infect Immun. 2000 Sep;68(9):5261-8
10948153
Pediatr Infect Dis J. 2000 Sep;19(9):911-6
11001126
Ann Otol Rhinol Laryngol. 1996 Mar;105(3):234-41
8615589
Antimicrob Agents Chemother. 2005 Jun;49(6):2467-73
15917548
Can J Microbiol. 1980 Jan;26(1):13-20
6773641
JAMA. 2002 Apr 3;287(13):1710-5
11926896
Mol Microbiol. 2008 Dec;70(5):1223-35
18990189
Infect Immun. 2004 Jan;72(1):106-13
14688087
J Appl Microbiol. 2008 Dec;105(6):2096-103
19120655
Mol Microbiol. 2001 Nov;42(3):777-93
11722742
Science. 1995 Jul 28;269(5223):496-512
7542800
J Infect Dis. 1994 Dec;170(6):1613-6
7996007
JAMA. 1998 Jan 28;279(4):296-9
9450714