Other vaccines targeting a single cell surface-associated antigen have failed clinical trials, for example, the iron surface determinant B (IsdB). identified evasion proteins. Interestingly, because Momelotinib Mesylate the different parts of neutrophil attack are redundant, the evasion molecules display redundant functions as well. Knowing how and with which proteinsS. aureusis evading the immune system is usually important in understanding the pathophysiology of this pathogen. This knowledge is crucial for the development of therapeutic approaches that aim to Momelotinib Mesylate clear staphylococcal infections. == INTRODUCTION == The Gram-positive bacteriumStaphylococcus aureusis considered a commensal bacterium because roughly one-third of the human population is usually colonized by it without developing disease (1). Colonization occurs in the human nose, whereby the host nasal microbiota plays a major role in promoting or inhibitingS. aureuscolonization (2). Despite the fact thatS. aureusis considered a commensal, nasal carriage ofS. aureusis linked to bacteremia (3). The bacterium may cause a range of infections, from cellulitis and superficial skin disease to abscesses, bacteremia, sepsis, endocarditis, and pneumonia (4). Moreover,S. aureushas been shown to adapt in its conversation with humans by increasing resistance Momelotinib Mesylate against methicillin and is currently a leading cause of human bacterial disease worldwide. Methicillin-resistantS. aureus(MRSA) was identified in the 1960s as a nosocomial pathogen, when hospitalized patients showed distinct risk factors for acquisition (5). The prevalence of methicillin resistance among nosocomialS. aureusisolates increased from 2.1% in 1975 to 35% in 1991 (6). MRSA epidemiology changed in the 1990s when infections of healthy individuals outside hospitals were reported. These strains, with increased virulence, were the first reports of community-acquired MRSA (7,8). Now, community-acquired MRSA has been reported as the leading cause of bacterial infections in the bloodstream, skin, soft tissue, and lower respiratory tract in developed countries (9). As a consequence, research interest in the pathophysiology ofS. aureushas increased. This extensive research during the past decades resulted in the identification and characterization of around 40 proteins which are able to evade various processes of the innate and adaptive immune system (10), the so-called immune evasion proteins. A list of these evasion molecules with their abbreviation, what they evade and location on which MGE is usually listed inTable 1. Proteomics has shown that around 100 to 200S. aureusproteins are secreted, many with a still unknown function (11). These unknown secreted proteins are potential evasion molecules, demonstrating that this identification and characterization of new evasion proteins is not yet complete and will most likely expand in the future. == TABLE 1. == Abbreviations of staphylococcal immune evasion proteins, what they evade, and on which MGE or paralogous gene cluster they are locateda MGE, mobile genetic element. The innate immune mechanisms that are inhibited: I, neutrophil extravasation; II, priming, chemotaxis, and activation of neutrophils; III, opsonization and phagocytosis; IV, NET formation; V, bacterial killing by neutrophils. IEC, immune evasion cluster; SaPI, staphylococcal pathogenicity island. vSa and vSa are clusters of paralogous genes that have evolved in situ, are nearly universally conserved inS. aureus, and are not MGEs. Many evasion proteins are targeted against neutrophils. This is not a surprise, because neutrophils are the most prominent leukocytes in blood, covering 60% of the leukocyte populace, and play a prominent role in fightingS. aureusinfection. They are equipped with various granules with specific content to kill both Gram-negative and Gram-positive bacteria (12,13). Neutrophils originate Momelotinib Mesylate and mature in the bone marrow and are then released into the bloodstream. There, these end-stage cells are induced to circulate and migrate toward the site of contamination by chemotactic signals produced both by the bacteria themselves and by host cells (13). Upon arrival at the contamination site, neutrophils Mouse monoclonal to KT3 Tag.KT3 tag peptide KPPTPPPEPET conjugated to KLH. KT3 Tag antibody can recognize C terminal, internal, and N terminal KT3 tagged proteins are able to eat microorganisms that are opsonized (labeled) by the complement system or immunoglobulins (antibodies). The complement system is especially important in clearing staphylococcal infections. Mice deficient in complement C5 showed decreased clearance ofS. aureusafter pulmonary and bloodstream infections (14,15). In addition, antibodies play an important role in fighting staphylococcal infections. Opsonization of bacteria subsequently leads to phagocytosis and, ultimately, killing of microbes, because neutrophils release the content of their antimicrobial granules and produce reactive oxygen species (ROS) (13). Impaired neutrophil function is usually linked to staphylococcal infections, as shown in multiple studies. For instance, patients suffering from congenital neutropenia often have severe infections, including staphylococcal infections, which can be fatal (16). Patients with chronic granulomatous disease have defects in their NADPH oxidase, which leads to impaired formation of.