Successful Treatment of Legionnaires' Disease with Tigecycline in an Immunocompromised Man with a Legion of Antibiotic Allergies.

Legionella species are Gram-negative bacilli that are relatively rare causes of community-acquired pneumonia but can be associated with significant morbidity and mortality if unrecognized or improperly treated. Limited data exist regarding the use of tigecycline, a third generation glycylcycline, in the treatment of Legionnaires' disease. We present an immunocompromised patient with Legionnaires' disease and allergies to both fluoroquinolones and macrolides, which are first-line treatment options for Legionnaires' disease. He was successfully treated using tigecycline, a third generation glycylcycline, indicating that tigecycline may serve as a safe and effective alternative therapeuticl option for treatment of Legionnaires' disease.

Structure-function relationships in the neuropeptide S receptor: molecular consequences of the asthma-associated mutation N107I.

Neuropeptide S (NPS) and its receptor (NPSR) are thought to have a role in asthma pathogenesis; a number of single nucleotide polymorphisms within NPSR have been shown to be associated with an increased prevalance of asthma. One such single nucleotide polymorphism leads to the missense mutation N107I, which results in an increase in the potency of NPS for NPSR. To gain insight into structure-function relationships within NPS and NPSR, we first carried out a limited structural characterization of NPS and subjected the peptide to extensive mutagenesis studies. Our results show that the NH(2)-terminal third of NPS, in particular residues Phe-2, Arg-3, Asn-4, and Val-6, are necessary and sufficient for activation of NPSR. Furthermore, part of a nascent helix within the peptide, spanning residues 5 through 13, acts as a regulatory region that inhibits receptor activation. Notably, this inhibition is absent in the asthma-linked N107I variant of NPSR, suggesting that residue 107 interacts with the aforementioned regulatory region of NPS. Whereas this interaction may be at the root of the increase in potency associated with the N107I variant, we show here that the mutation also causes an increase in cell-surface expression of the mutant receptor, leading to a concomitant increase in the maximal efficacy (E(max)) of NPS. Our results identify the key residues of NPS involved in NPSR activation and suggest a molecular basis for the functional effects of the N107I mutation and for its putative pathophysiological link with asthma.