Abstract
Pneumococci frequently colonize the upper respiratory tract, and these pneumococci are believed to act as a reservoir for infection of the lower respiratory tract and bacteremia. We investigated how the pneumococcal toxin pneumolysin affects the capacity of pneumococci to infect the upper and lower respiratory tract of the mouse. Wild-type Streptococcus pneumoniae serotype 2 and 3 strains, a serotype 2 pneumolysin-deficient mutant, and a serotype 2 mutant with the pneumolysin gene reinserted were used to study differences in colonization and disease. In addition, we also examined a pneumococcal chimeric mutant (capsule type switched from serotype 2 to serotype 3) to gain further insight into the role that capsule plays in nasopharyngeal infection. Absence of pneumolysin was found to be associated with significantly lower numbers of pneumococci in the nasopharynx, trachea, and lungs. Differences in pneumococcal capsule type were found to have significant effects on pneumococcal infection of the nasopharynx, trachea, and lungs. However, it was the combination of capsule type and genetic background that was important, and the influence of this combination varied with the site of infection. For example, in the nasopharynx the wild-type serotype 3 strain and the capsule-switched mutant behaved similarly, whereas in the lungs the mutant that was switched to serotype 3 survived less well than the wild-type serotype 3 strain. The combination of capsule type and genetic background also determined virulence. Thus, the wild-type serotype 3 strain was virulent, whereas the capsule-switched mutant was avirulent.
MeSH Terms
Animals
Bacterial Capsules/genetics,physiology
Bacterial Proteins
Cytotoxins/genetics,physiology
Disease Models, Animal
Female
Lung/microbiology
Mice
Nasopharynx/microbiology
Pneumococcal Infections/microbiology
Respiratory Tract Infections/microbiology
Streptococcus pneumoniae/genetics,pathogenicity
Streptolysins/genetics,physiology
Trachea/microbiology
Virulence
Chemicals
Bacterial Proteins
Cytotoxins
Streptolysins
plY protein, Streptococcus pneumoniae
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kadioglu Aras
Department of Microbiology and Immunology, University of Leicester, Leicester, LE1 United Kingdom.
[email protected]
Taylor Sally
Iannelli Francesco
Pozzi Gianni
Mitchell Tim J
Andrew Peter W
References (27)
27 references, click to expand
-
Interaction of pneumolysin-sufficient and -deficient isogenic variants of Streptococcus pneumoniae with human respiratory mucosa.
Infect Immun. 1995 Feb;63(2):442-7
PMID: 7822008
-
The pneumococcal problem.
BMJ. 1996 Jun 15;312(7045):1521-5
PMID: 8646147
-
Host cellular immune response to pneumococcal lung infection in mice.
Infect Immun. 2000 Feb;68(2):492-501
PMID: 10639409
-
Receptor specificity of adherence of Streptococcus pneumoniae to human type-II pneumocytes and vascular endothelial cells in vitro.
Microb Pathog. 1994 Dec;17(6):361-74
PMID: 7752878
-
Pneumolysin stimulates production of tumor necrosis factor alpha and interleukin-1 beta by human mononuclear phagocytes.
Infect Immun. 1994 Apr;62(4):1501-3
PMID: 8132361
-
Pneumococcal adhesion to human pharyngeal cells.
Scand J Infect Dis Suppl. 1982;33:96-7
PMID: 6958030
-
STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES : INDUCTION OF TRANSFORMATION BY A DESOXYRIBONUCLEIC ACID FRACTION ISOLATED FROM PNEUMOCOCCUS TYPE III.
J Exp Med. 1944 Feb 1;79(2):137-58
PMID: 19871359
-
Adherence of Streptococcus pneumoniae to respiratory epithelial cells is inhibited by sialylated oligosaccharides.
Infect Immun. 1998 Apr;66(4):1439-44
PMID: 9529065
-
Interferon-gamma enhances expression of secretory component, the epithelial receptor for polymeric immunoglobulins.
J Immunol. 1987 Jun 15;138(12):4303-6
PMID: 3108385
-
The biology of pneumococcal infection.
Pediatr Res. 1997 Sep;42(3):253-8
PMID: 9284261
-
Reduced virulence of a defined pneumolysin-negative mutant of Streptococcus pneumoniae.
Infect Immun. 1989 Jul;57(7):2037-42
PMID: 2731982
-
Competence for genetic transformation in encapsulated strains of Streptococcus pneumoniae: two allelic variants of the peptide pheromone.
J Bacteriol. 1996 Oct;178(20):6087-90
PMID: 8830714
-
Amino acid changes affecting the activity of pneumolysin alter the behaviour of pneumococci in pneumonia.
Microb Pathog. 1998 Mar;24(3):167-74
PMID: 9514638
-
Pneumococcal licD2 gene is involved in phosphorylcholine metabolism.
Mol Microbiol. 1999 Mar;31(5):1477-88
PMID: 10200966
-
Use of green fluorescent protein in visualisation of pneumococcal invasion of broncho-epithelial cells in vivo.
FEMS Microbiol Lett. 2001 Jan 1;194(1):105-10
PMID: 11150674
-
Some aspects of the pneumococcal carrier state.
J Antimicrob Chemother. 1986 Jul;18 Suppl A:35-45
PMID: 3745031
-
Pneumolysin activates phospholipase A in pulmonary artery endothelial cells.
Infect Immun. 1994 Sep;62(9):3829-36
PMID: 8063399
-
Aspects on the interaction of Streptococcus pneumoniae and Haemophilus influenzae with human respiratory tract mucosa.
Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 2):S187-91
PMID: 8876540
-
Identification of an active disaccharide unit of a glycoconjugate receptor for pneumococci attaching to human pharyngeal epithelial cells.
J Exp Med. 1983 Aug 1;158(2):559-70
PMID: 6886624
-
The effect of Streptococcus pneumoniae pneumolysin on human respiratory epithelium in vitro.
Microb Pathog. 1990 Oct;9(4):275-84
PMID: 2097494
-
Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor.
Nature. 1995 Oct 5;377(6548):435-8
PMID: 7566121
-
Pneumolysin in pneumococcal adherence and colonization.
Microb Pathog. 1998 Dec;25(6):337-42
PMID: 9895272
-
Inhibition of human polymorphonuclear leukocyte respiratory burst, bactericidal activity, and migration by pneumolysin.
Infect Immun. 1983 Sep;41(3):1212-6
PMID: 6885160
-
Effect of genetic switching of capsular type on virulence of Streptococcus pneumoniae.
Infect Immun. 1994 May;62(5):1813-9
PMID: 8168944
-
Establishment of a Streptococcus pneumoniae nasopharyngeal colonization model in adult mice.
Microb Pathog. 1997 Sep;23(3):127-37
PMID: 9281471
-
Complement activation and antibody binding by pneumolysin via a region of the toxin homologous to a human acute-phase protein.
Mol Microbiol. 1991 Aug;5(8):1883-8
PMID: 1766369
-
The role of pneumolysin and autolysin in the pathology of pneumonia and septicemia in mice infected with a type 2 pneumococcus.
J Infect Dis. 1995 Jul;172(1):119-23
PMID: 7797901