Presence or absence of lipopolysaccharide O antigens affects type III secretion by Pseudomonas aeruginosa.
Pseudomonas aeruginosa is one of the major causative agents of mortality and morbidity in hospitalized patients due to a multiplicity of virulence factors associated with both chronic and acute infections. Acute P. aeruginosa infection is primarily mediated by planktonic bacteria expressing the type III secretion system (TTSS), a surface-attached needle-like complex that injects cytotoxins directly into eukaryotic cells, causing cellular damage. Lipopolysaccharide (LPS) is the principal surface-associated virulence factor of P. aeruginosa. This molecule is known to undergo structural modification (primarily alterations in the A- and B-band O antigen) in response to changes in the mode of life (e.g., from biofilm to planktonic). Given that LPS exhibits structural plasticity, we hypothesized that the presence of LPS lacking O antigen would facilitate eukaryotic intoxication and that a correlation between the LPS O-antigen serotype and TTSS-mediated cytotoxicity would exist. Therefore, strain PAO1 (A+ B+ O-antigen serotype) and isogenic mutants with specific O-antigen defects (A+ B-, A- B+, and A- B-) were examined for TTSS expression and cytotoxicity. A strong association existed in vitro between the absence of the large, structured B-band O antigen and increased cytotoxicity of these strains. In vivo, all three LPS mutant strains demonstrated significantly increased lung injury compared to PAO1. Clinical strains lacking the B-band O antigen also demonstrated increased TTSS secretion. These results suggest the existence of a cooperative association between LPS O-antigen structure and the TTSS in both laboratory and clinical isolates of P. aeruginosa.
Augustin
D K
DK
Biology Department, California State University, San Francisco, CA 94142, USA.
Song
Y
Y
Baek
M S
MS
Sawa
Y
Y
Singh
G
G
Taylor
B
B
Rubio-Mills
A
A
Flanagan
J L
JL
Wiener-Kronish
J P
JP
Lynch
S V
SV
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001980:Bronchi / Q000166:cytology / Q000382:microbiology; D002460:Cell Line; D003603:Cytotoxins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D019081:O Antigens / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D003603:Cytotoxins; D019081:O Antigens; D037521:Virulence Factors