Surfactant protein A binds Mycoplasma pneumoniae with high affinity and attenuates its growth by recognition of disaturated phosphatidylglycerols.
Surfactant Protein A (SP-A) is an abundant, multifunctional lectin that resides within the bronchoalveolar compartment of the lung and plays an important role in the innate immunity of the organ. Mycoplasma pneumoniae is a human pathogen that resides in the same compartment as SP-A, and we examined the interaction between the two. Preparations of human and rat SP-A recognized the mycoplasma with high affinity in the presence of Ca(2+), exhibiting apparent K(')(d) values in the nanomolar range. Membranes prepared from the microbe also bound human and rat SP-A with similar characteristics and affinity to the intact cells. The ligand for SP-A was insensitive to proteolysis. Lipid extracts prepared from the mycoplasma, bound SP-A with high affinity when examined by ligand blot analysis. These lipid extracts were also potent competitive inhibitors (IC(50) = 0.2 nM) of human SP-A binding to mycoplasma membranes. The major lipid ligands for the protein identified by mass spectrometry are a group of disaturated phosphatidylglycerols. The addition of SP-A to cultures of M. pneumoniae markedly attenuated the growth of the organism assessed by colony formation, metabolic activity, and DNA replication. The bacteriostatic effects of SP-A were reversed by dipalmitoylphosphatidylglycerol. These findings demonstrate that human SP-A can play a direct role in antibody-independent immunity to M. pneumoniae by interacting with lipid ligands expressed on the surface of the organism and implicate SP-A in the immediate host response to the bacteria.
Piboonpocanun
Surapon
S
Program in Cell Biology, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Chiba
Hirofumi
H
Mitsuzawa
Hiroaki
H
Martin
Wesley
W
Murphy
Robert C
RC
Harbeck
Ronald J
RJ
Voelker
Dennis R
DR
D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D008024:Ligands; D009177:Mycoplasma pneumoniae / Q000254:growth & development / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000378:metabolism*; D011019:Pneumonia, Mycoplasma / Q000378:metabolism / Q000382:microbiology; D011485:Protein Binding; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology / Q000378:metabolism*; D051381:Rats
D008024:Ligands; D010715:Phosphatidylglycerols; D037662:Pulmonary Surfactant-Associated Protein A; C030345:1,2-dipalmitoylphosphatidylglycerol