Staphylococcus aureus Strains Lacking d-Alanine Modifications of Teichoic Acids Are Highly Susceptible to Human Neutrophil Killing and Are Virulence Attenuated in Mice

• Published in: The Journal of infectious diseases Vol. 186; no. 2; pp. 214 - 219
• Main Authors: Collins, L. Vincent, Kristian, Sascha A., Weidenmaier, Christopher, Faigle, Marion, van Kessel, Kok P. M., van Strijp, Jos A. G., Götz, Friedrich, Neumeister, Birgid, Peschel, Andreas
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.07.2002; University of Chicago Press
• Subjects: Alanine - metabolism; alpha-Defensins - metabolism; Animals; Anti-Bacterial Agents - metabolism; Antimicrobials; Arthritis; Bacteria; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; Blood; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Humans; Infections; Major Articles; Membrane Transport Proteins - metabolism; Mice; Microbiology; Monocytes; Mutation; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Phagocytosis; Staphylococcal Infections - immunology; Staphylococcal Infections - metabolism; Staphylococcal Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - metabolism; Staphylococcus aureus - pathogenicity; Teichoic acids; Teichoic Acids - genetics; Teichoic Acids - metabolism; Virulence; Human; Resistance; Virulence; Bacteria; Micrococcales; Host agent relation; Micrococcaceae; Neutrophil; Attenuated strain; Staphylococcus aureus; Teichoic acids; Bactericidal effect
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/341454

Staphylococcus aureus is resistant to α-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