Pneumococcal zinc metalloproteinase ZmpC cleaves human matrix metalloproteinase 9 and is a virulence factor in experimental pneumonia.
The ZmpC zinc metalloproteinase of Streptococcus pneumoniae, annotated in the type 4 genome as SP0071, was found to cleave human matrix metalloproteinase 9 (MMP-9). The previously described IgA protease activity was confirmed to be specifically linked to the IgA1-protease/SP1154 zinc metalloproteinase. MMP-9 is a protease cleaving extracellular matrix gelatin and collagen and is activated by proteolytic cleavage like most proteases. MMP-9 is a human protease and is involved in a variety of physiological and pathological matrix degrading processes, including tissue invasion of metastases and opening of the blood-brain barrier. While TIGR4 (serotype 4) and G54 (serotype 19) pneumococcal genome strains have a highly conserved copy of zmpC, the genome of R6 (a derivative of serotype 2 D39 strain) lacks zmpC. Both the analysis for zmpC presence and MMP-9 cleavage activity in various pneumococcal strains showed correlation of ZmpC with MMP-9 cleavage activity. When assaying clinical isolates of S. pneumoniae, the zmpC gene was not found in any of the nasal and conjunctival swab isolates, but it was present in 1 out of 13 meningitis isolates and in 6 out of 11 pneumonia isolates. In a murine pneumonia model, infection with a zmpC-mutant reduced mortality at 3-4 days post-infection by 75%, when compared with infection with wild-type strains. These data indicate that the ZmpC pneumococcal protease may play a role in pneumococcal virulence and pathogenicity in the lung.
Oggioni
Marco R
MR
Dipartimento di Biologia Molecolare, Laboratorio di Microbiologia Molecolare e Biotecnologia, Università di Siena, Siena, Italy. oggioni@unisi.it
Memmi
Guido
G
Maggi
Tiziana
T
Chiavolini
Damiana
D
Iannelli
Francesco
F
Pozzi
Gianni
G
D000281:Administration, Intranasal; D000818:Animals; D001812:Blood-Brain Barrier; D001826:Body Fluids / Q000382:microbiology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D018390:Gene Targeting; D005838:Genotype; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000382:microbiology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008586:Meningitis, Pneumococcal / Q000201:enzymology / Q000382:microbiology; D008666:Metalloendopeptidases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D010641:Phenotype; D011018:Pneumonia, Pneumococcal / Q000201:enzymology / Q000382:microbiology*; D012697:Serine Endopeptidases / Q000502:physiology; D013045:Species Specificity; D013296:Streptococcus pneumoniae / Q000145:classification / Q000201:enzymology* / Q000302:isolation & purification / Q000472:pathogenicity; D014774:Virulence
C412019:ZmpB enzyme; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase; D008666:Metalloendopeptidases; C478168:ZmpC protein, Streptococcus pneumoniae; D020780:Matrix Metalloproteinase 9