Staphylococcus aureus strains lacking D-alanine modifications of teichoic acids are highly susceptible to human neutrophil killing and are virulence attenuated in mice.
Staphylococcus aureus is resistant to alpha-defensins, antimicrobial peptides that play an important role in oxygen-independent killing of human neutrophils. The dlt operon mediates d-alanine incorporation into teichoic acids in the staphylococcal cell envelope and is a determinant of defensin resistance. By using S. aureus wild-type (WT) and Dlt- bacteria, the relative contributions of oxygen-dependent and -independent antimicrobial phagocyte components were analyzed. The Dlt- strain was efficiently killed by human neutrophils even in the absence of a functional respiratory burst, whereas the killing of the WT organism was strongly diminished when the respiratory burst was inhibited. Human monocytes, which do not produce defensins, inactivated the WT and Dlt- bacteria with similar efficiencies. In addition, mice injected with the Dlt- strain had significantly lower rates of sepsis and septic arthritis and fewer bacteria in the kidneys, compared with mice infected with the WT strain.
Department of Rheumatology, University of Göteborg, Göteborg, Sweden. vincent.collins@immuno.gu.se
L Vincent
LV
Collins
Sascha A
SA
Kristian
Christopher
C
Weidenmaier
Marion
M
Faigle
Kok P M
KP
Van Kessel
Jos A G
JA
Van Strijp
Friedrich
F
Götz
Birgid
B
Neumeister
Andreas
A
Peschel
D000409:Alanine / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D009000:Monocytes; D009154:Mutation; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis; D013203:Staphylococcal Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000378:metabolism / Q000472:pathogenicity*; D013682:Teichoic Acids / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D023084:alpha-Defensins / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C118498:DltB protein, Staphylococcus; D026901:Membrane Transport Proteins; D013682:Teichoic Acids; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D000409:Alanine