We thank Dr Fuminobu Yoshimura and Ms Mikie Sato for help with PMF analysis. This work was supported

by Grants-in-Aid for Scientific Research (to K.S. and K.N.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Global COE Program at Nagasaki University (to K.N.). “
“The iron-regulated surface determinant LY294002 proteins (Isd) of Staphylococcus aureus are expressed during iron limitation and have been proposed to be involved in the scavenging of iron from heme. In this study, the genes encoding the surface proteins IsdA, IsdB, and IsdH were inactivated in order to determine their combined role. The triple mutant was found to have no defect in growth under any conditions of iron limitation tested. Also using a mouse septic arthritis model of S. aureus systemic disease, no significant difference in bacterial load was observed for the triple mutant, compared

with its otherwise isogenic parent. The Gram-positive pathogen Staphylococcus aureus is the most commonly identified antibiotic-resistant cause of infection in many parts of the world including East Asia, America, and Europe (Foster, 2004). The natural niche for S. aureus, however, is as a commensal in the human nose, being carried by approximately 30% of the population (Wenzel & Perl, 1995). Thus, it is extremely selleck products prevalent in the human environment making its eradication more difficult and contributing to potential infections. As well as being a commensal of humans,

S. aureus can cause a variety of life-threatening diseases (Emori & PAK5 Gaynes, 1993). Thus, the organism is very adaptable colonizing a wide range of niches. Success of S. aureus requires the ability to respond to the host environment in order to grow and survive. A key nutritional factor that can limit the growth of bacteria in vivo is iron availability (Bullen, 1985). In fact, the sequestration of iron by mammalian hosts is a mechanism to stop the invasion of pathogens. Thus, iron deprivation is an important signal to which S. aureus responds using such regulatory systems as Fur (Horsburgh et al., 2001a). Fur responds to the lack of iron (as a marker of host interaction) by the derepression of a number of iron acquisition systems, including siderophore production and a heme iron uptake system (Heinrichs et al., 1999; Horsburgh et al., 2001a). Also negatively regulated by Fur is the expression of several surface proteins (Dryla et al., 2003). These iron-regulated surface determinants (Isd) are found covalently bound to the cell wall peptidoglycan, by the action of sortases, and thus interface with the external milieu. There are four cell wall–bound Isd proteins (IsdA, IsdB, IsdC, and IsdH) in S. aureus, and all have varying numbers of NEAT domains, which have been proposed to be involved in iron acquisition (Mazmanian et al., 2003).