TY - JOUR
T1 - Human complement activation by smooth and rough Proteus mirabilis lipopolysaccharides
AU - Kaca, Wiesław
AU - Arabski, Michał
AU - Fudała, Rafał
AU - Holmström, Eva
AU - Sjöholm, Anders
AU - Weintraub, Andrej
AU - Futoma-Kołoch, Bozena
AU - Bugla-Płoskońska, Gabriela
AU - Doroszkiewicz, Włodzimierz
N1 - Funding Information:
Acknowledgment: The work was supported by grants from Karolinska Institute, Sweden (for W. Kaca, A. Weintraub) and grant N N304 4114 33 from the Ministry of Science and Higher Education, Poland.
PY - 2009/10
Y1 - 2009/10
N2 - Introduction: Proteus mirabilis bacilli play an important role in human urinary tract infections, bacteremia, and rheumatoid arthritis. The authors previously studied human complement C3 conversion by smooth-form P. mirabilis O10, O23, O30, and O43 lipopolysaccharides (LPSs) and showed that smooth Proteus LPSs fragmented C3 in a dose- and time-dependent manner. In the present study, one smooth P. mirabilis S1959 and its two polysaccharide-truncated LPSs isolated from an R mutant strain were used to study the C3 conversion. Materials and Methods: The conversion of C3 to C3c by smooth and rough P. mirabilis LPSs was studied by capture ELISA and crossed immunoelectrophoresis. Proteins isolated from the outer membrane were analyzed by discontinuous sodium dodecyl sulfate gel electrophoresis. Results: The smooth P. mirabilis S1959 (O3) strain was resistant to the bactericidal activity of human serum, in contrast to the Ra and Re mutant strains. The presence of an exposed core oligosaccharide in R110 LPS was not sufficient to protect the strain from serum-dependent killing. In addition to LPS structure, the outer-membrane proteins may also play roles in protecting the smooth P. mirabilis S1959 (O3) strain from the bactericidal action of serum. It was shown that the Ra P. mirabilis R110 and the Re P. mirabilis R45 mutants possess very different OMP compositions from that of the P. mirabilis S 1959 strain. Conclusion: Regardless of the complement resistance of the P. mirabilis strains, the S1959, R110, and R45 LPSs fragmented C3 and induced C3c neo-antigen exposure. The use of complement-deficient human serum allows the conclusion that the Re-type P. mirabilis R45 LPS fragmented C3 by the antibody-independent classical pathway.
AB - Introduction: Proteus mirabilis bacilli play an important role in human urinary tract infections, bacteremia, and rheumatoid arthritis. The authors previously studied human complement C3 conversion by smooth-form P. mirabilis O10, O23, O30, and O43 lipopolysaccharides (LPSs) and showed that smooth Proteus LPSs fragmented C3 in a dose- and time-dependent manner. In the present study, one smooth P. mirabilis S1959 and its two polysaccharide-truncated LPSs isolated from an R mutant strain were used to study the C3 conversion. Materials and Methods: The conversion of C3 to C3c by smooth and rough P. mirabilis LPSs was studied by capture ELISA and crossed immunoelectrophoresis. Proteins isolated from the outer membrane were analyzed by discontinuous sodium dodecyl sulfate gel electrophoresis. Results: The smooth P. mirabilis S1959 (O3) strain was resistant to the bactericidal activity of human serum, in contrast to the Ra and Re mutant strains. The presence of an exposed core oligosaccharide in R110 LPS was not sufficient to protect the strain from serum-dependent killing. In addition to LPS structure, the outer-membrane proteins may also play roles in protecting the smooth P. mirabilis S1959 (O3) strain from the bactericidal action of serum. It was shown that the Ra P. mirabilis R110 and the Re P. mirabilis R45 mutants possess very different OMP compositions from that of the P. mirabilis S 1959 strain. Conclusion: Regardless of the complement resistance of the P. mirabilis strains, the S1959, R110, and R45 LPSs fragmented C3 and induced C3c neo-antigen exposure. The use of complement-deficient human serum allows the conclusion that the Re-type P. mirabilis R45 LPS fragmented C3 by the antibody-independent classical pathway.
KW - Complement
KW - Lipopolysaccharide
KW - Outer-membrane protein
KW - Proteus mirabilis
UR - http://www.scopus.com/inward/record.url?scp=69549114276&partnerID=8YFLogxK
U2 - 10.1007/s00005-009-0043-8
DO - 10.1007/s00005-009-0043-8
M3 - Article
C2 - 19707721
AN - SCOPUS:69549114276
SN - 0004-069X
VL - 57
SP - 383
EP - 391
JO - Archivum Immunologiae et Therapiae Experimentalis
JF - Archivum Immunologiae et Therapiae Experimentalis
IS - 5
ER -