Staphylococcus aureus is one of the most frequent worldwide causes of morbidity and mortality due to an infectious agent. This pathogen can cause a wide variety of diseases, ranging from moderately severe skin infections to fatal pneumonia and sepsis. Treatment of S. aureus infections is complicated by antibiotic resistance and a working vaccine is not available. There has been ongoing and increasing interest in the extraordinarily high number of toxins and other virulence determinants that S. aureus produces and how they impact disease. In this review, we will give an overview of how S. aureus initiates and maintains infection and discuss the main determinants involved. A more in-depth understanding of the function and contribution of S. aureus virulence determinants to S. aureus infection will enable us to develop anti-virulence strategies to counteract the lack of an anti-S. aureus vaccine and the ever-increasing shortage of working antibiotics against this important pathogen.

Positively charged antimicrobial peptides with membrane-damaging activity are produced by animals and humans as components of their innate immunity against bacterial infections and also by many bacteria to inhibit competing microorganisms.Staphylococcus aureus and Staphylococcus xylosus, which tolerate high concentrations of several antimicrobial peptides, were mutagenized to identify genes responsible for this insensitivity. Several mutants with increased sensitivity were obtained, which exhibited an altered structure of teichoic acids, major components of the Gram-positive cell wall. The mutant teichoic acids lacked d-alanine, as a result of which the cells carried an increased negative surface charge. The mutant cells bound fewer anionic, but more positively charged proteins. They were sensitive to human defensin HNP1–3, animal-derived protegrins, tachyplesins, and magainin II, and to the bacteria-derived peptides gallidermin and nisin. The mutated genes shared sequence similarity with thedlt genes involved in the transfer of d-alanine into teichoic acids from other Gram-positive bacteria. Wild-type strains bearing additional copies of the dlt operon produced teichoic acids with higher amounts of d-alanine esters, bound cationic proteins less effectively and were less sensitive to antimicrobial peptides. We propose a role of thed-alanine-esterified teichoic acids which occur in many pathogenic bacteria in the protection against human and animal defense systems.