RT Journal Article
T1 Synergistic action of antimicrobial lung proteins againstKlebsiella pneumoniae
A1 Fraile Ágreda, Víctor
A1 Cañadas Benito, Olga
A1 Weaver, Timothy E.
A1 Casals Carro, María Cristina
AB As key components of innate immunity, lung antimicrobial proteins play a critical role in warding off invading respiratory pathogens. Lung surfactant protein A (SP-A) exerts synergistic antimicrobial activity with the N-terminal segment of the SP-B proprotein (SP-BN) against Klebsiella pneumoniae K2 in vivo. However, the factors that govern SP-A/SP-BN antimicrobial activity are still unclear. The aim of this study was to identify the mechanisms by which SP-A and SP-BN act synergistically against K. pneumoniae, which is resistant to either protein alone. The effect of these proteins on K. pneumoniae was studied by membrane permeabilization and depolarization assays and transmission electron microscopy. Their effects on model membranes of the outer and inner bacterial membranes were analyzed by differential scanning calorimetry and membrane leakage assays. Our results indicate that the SP-A/SP-BN complex alters the ultrastructure of K. pneumoniae by binding to lipopolysaccharide molecules present in the outer membrane, forming packing defects in the membrane that may favor the translocation of both proteins to the periplasmic space. The SP-A/SP-BN complex depolarized and permeabilized the inner membrane, perhaps through the induction of toroidal pores. We conclude that the synergistic antimicrobial activity of SP-A/SP-BN is based on the capability of this complex, but not either protein alone, to alter the integrity of bacterial membranes.
PB MDPI
SN 1422-0067, Electronic: 1422-0067
YR 2021
FD 2021-10-15
LK https://hdl.handle.net/20.500.14352/4877
UL https://hdl.handle.net/20.500.14352/4877
LA eng
NO Ministerio de Ciencia e Innovación (MICINN)
NO National Institute of Health (U.S.)
NO Universidad Complutense de Madrid (UCM)
DS Docta Complutense
RD 6 jul 2025