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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tibs.2010.04.006 Byline: Lage Cerenius (1), Shun-ichiro Kawabata (2), Bok Luel Lee (3), Masaru Nonaka (4), Kenneth Soderhall (1) Abstract: Bacteria and other potential pathogens are cleared rapidly from the body fluids of invertebrates by the immediate response of the innate immune system. Proteolytic cascades, following their initiation by pattern recognition proteins, control several such reactions, notably coagulation, melanisation, activation of the Toll receptor and complement-like reactions. However, there is considerable variation among invertebrates and these cascades, although widespread, are not present in all phyla. In recent years, significant progress has been made in identifying and characterizing these cascades in insects. Notably, recent work has identified several connections and shared principles among the different pathways, suggesting that cross-talk between them may be common. Author Affiliation: (1) Department of Comparative Physiology, Uppsala University, Norbyvagen 18A, SE-752 36 Uppsala, Sweden (2) Department of Biology, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-Ku, Fukuoka 812-8581, Japan (3) National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Jangjeon Dong, Gumjeong Gu, Busan 609-735, Korea (4) Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Lipoteichoic acid (LTA) is one of two anionic polymers on the surface of the gram-positive bacterium Staphylococcus aureus. LTA is critical for the bacterium-host cell interaction and has recently been shown to be required for cell growth and division. To determine additional biological roles of LTA, we found it necessary to identify permissive conditions for the growth of an LTA-deficient mutant. We found that an LTA-deficient S. aureus [DELTA]ltaS mutant could grow at 30[degrees]C but not at 37[degrees]C. Even at the permissive temperature, [DELTA]ltaS mutant cells had aberrant cell division and separation, decreased autolysis, and reduced levels of peptidoglycan hydrolases. Upshift of [DELTA]ltaS mutant cells to a nonpermissive temperature caused an inability to exclude Sytox green dye. A high-osmolarity growth medium remarkably rescued the colony-forming ability of the [DELTA]ltaS mutant at 37[degrees]C, indicating that LTA synthesis is required for growth under low-osmolarity conditions. In addition, the [DELTA]ltaS mutation was found to be synthetically lethal with the [DELTA]tagO mutation, which disrupts the synthesis of the other anionic polymer, wall teichoic acid (WTA), at 30[degrees]C, suggesting that LTA and WTA compensate for one another in an essential function.

In the complement system, the opsonin C3b binds to the bacterial cell surface and mediates the opsonophagocytosis. However, the cell-wall protein SdrE of Staphylococcus aureus inhibits the C3b activity by recruiting the complement regulatory protein factor H (fH). SdrE binds to fH via its N-terminal N2N3 domain, which are also found in six other staphylococcal cell-wall proteins. In this study, we report that not only the N2N3 domain of SdrE but also those of ClfA, FnbpA and FnbpB can bind to fH. When immobilized on a microplate, the N2N3 domains recruited fH and enhanced the factor I (fI)-mediated cleavage of C3b. When mixed with fH and S. aureus cells, the N2N3 domains inhibited the fH binding to S. aureus cells and reduced the fI-mediated C3b cleavage on the bacterial cell surface. The F(ab)′2 fragments of the rabbit N2N3 antibodies also inhibited the fH binding to the S. aureus cell surface. When added to human blood, the N2N3 antibodies or the N2N3 domain proteins significantly increased the bactericidal activity. Based on these results, we conclude that, in S. aureus , not only SdrE but also ClfA, FnbpA and FnbpB can contribute to the inhibition of C3b-mediated opsonophagocytosis. [ABSTRACT FROM AUTHOR]