In:
Infection and Immunity, American Society for Microbiology, Vol. 70, No. 12 ( 2002-12), p. 6880-6890
Abstract:
Recently, it was reported that a streptococcal Mac protein (designated Mac 5005 ) made by serotype M1 group A Streptococcus (GAS) is a homologue of human CD11b that inhibits opsonophagocytosis and killing of GAS by human polymorphonuclear leukocytes (PMNs) (B. Lei, F. R. DeLeo, N. P. Hoe, M. R. Graham, S. M. Mackie, R. L. Cole, M. Liu, H. R. Hill, D. E. Low, M. J. Federle, J. R. Scott, and J. M. Musser, Nat. Med. 7: 1298-1305, 2001). To study mac variation and expression of the Mac protein, the gene in 67 GAS strains representing 36 distinct M protein serotypes was sequenced. Two distinct genetic complexes were identified, and they were designated complex I and complex II. Mac variants in each of the two complexes were closely related, but complex I and complex II variants differed on average at 50.66 ± 5.8 amino acid residues, most of which were located in the middle one-third of the protein. Complex I Mac variants have greater homology with CD11b than complex II variants. GAS strains belonging to serotypes M1 and M3, the most abundant M protein serotypes responsible for human infections in many case series, have complex I Mac variants. The mac gene was cloned from representative strains assigned to complexes I and II, and the Mac proteins were purified to apparent homogeneity. Both Mac variants had immunoglobulin G (IgG)-endopeptidase activity. In contrast to Mac 5005 (complex I), Mac 8345 (complex II) underwent autooxidation of its cysteine residues, resulting in the loss of IgG-endopeptidase activity. A Mac 5005 Cys94Ala site-specific mutant protein was unable to cleave IgG but retained the ability to inhibit IgG-mediated phagocytosis by human PMNs. Thus, the IgG-endopeptidase activity was not essential for the key biological function of Mac 5005 . Although Mac 5005 and Mac 8345 each have an Arg-Gly-Asp (RGD) motif, the proteins differed in their interactions with human integrins α v β 3 and α IIb β 3 . Binding of Mac 5005 to integrins α v β 3 and α IIb β 3 was mediated primarily by the RGD motif in Mac 5005 , whereas binding of Mac 8345 involved the RGD motif and a region in the middle one-third of the molecule whose sequence is different in Mac 8345 and Mac 5005 . Taken together, the data add to the emerging theme in GAS pathogenesis that allelic variation in virulence genes contributes to fundamental differences in host-pathogen interactions among strains.
Type of Medium:
Online Resource
ISSN:
0019-9567
,
1098-5522
DOI:
10.1128/IAI.70.12.6880-6890.2002
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2002
detail.hit.zdb_id:
1483247-1
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