Defining the Role of the Streptococcus agalactiae Sht-Family Proteins in Zinc Acquisition and Complement Evasion.

Streptococcus agalactiae is not only part of the human intestinal and urogenital microbiota but is also a leading cause of septicemia and meningitis in neonates. Its ability to cause disease depends upon the acquisition of nutrients from its environment, including the transition metal ion zinc. The primary zinc acquisition system of the pathogen is the Adc/Lmb ABC permease, which is essential for viability in zinc-restricted environments. Here, we show that in addition to the AdcCB transporter and the three zinc-binding proteins, Lmb, AdcA, and AdcAII, S. agalactiae zinc homeostasis also involves two streptococcal histidine triad (Sht) proteins. Sht and ShtII are required for zinc uptake via the Lmb and AdcAII proteins with apparent overlapping functionality and specificity. Both Sht-family proteins possess five-histidine triad motifs with similar hierarchies of importance for Zn homeostasis. Independent of its contribution to zinc homeostasis, Sht has previously been reported to bind factor H leading to predictions of a contribution to complement evasion. Here, we investigated ShtII to ascertain whether it had similar properties. Analysis of recombinant Sht and ShtII reveals that both proteins have similar affinities for factor H binding. However, neither protein aided in resistance to complement in human blood. These findings challenge prior inferences regarding the in vivo role of the Sht proteins in resisting complement-mediated clearance.IMPORTANCE This study examined the role of the two streptococcal histidine triad (Sht) proteins of Streptococcus agalactiae in zinc homeostasis and complement resistance. We showed that Sht and ShtII facilitate zinc homeostasis in conjunction with the metal-binding proteins Lmb and AdcAII. Here, we show that the Sht-family proteins are functionally redundant with overlapping roles in zinc uptake. Further, this work reveals that although the Sht-family proteins bind to factor H in vitro this did not influence survival in human blood.

[The relationship between aneurysmal subarachnoid hemorrhage and meteorological parameters based on a series of 236 French patients]. / Relations entre hémorragies sous-arachnoïdiennes par rupture anévrysmale et paramètres météorologiques à partir d'une série française de 236 patients.

Subarachnoid hemorrhage (SAH) is a sudden and potentially severe event with mortality rates ranging between 24 and 30 % depending on the initial clinical condition. Studies have attempted to assess the possible influence of meteorological parameters on the occurrence of SAH. However, this idea remains very controversial and the results vary widely from one study to another. Our study is the second largest French series, and first performed in a homogeneous series of patients. The aim of our study was to attempt to establish a relationship between the weather (i.e.) temperature variations and daily variations of atmospheric pressure in the days before the onset of SAH and the same day and the occurrence of non-traumatic SAH in a homogeneous population of 236 patients from a single center, over a period of 7 years (2002 to 2008). This retrospective study does not suggest any relationship between the occurrence of SAH and meteorological data studied. Moreover, no relationship was observed between mean changes in temperature or pressure and the occurrence of SAH, that the day of the bleeding or the days preceding the SAH. However, a female predominance was observed and a relatively high mortality rate of 18.3 %. The distribution of the occurrence of an SAH was random. As it seems impossible to provide logistics and organization of care for non-traumatic SAH, the care system must remain vigilant throughout the year.