The human pathogenic fungus Cryptococcus neoformans secretes a phospholipase enzyme that demonstrates phospholipase B (PLB), lysophospholipase hydrolase and lysophospholipase transacylase activities. This enzyme has been postulated to be a cryptococcal virulence factor. We cloned a phospholipase‐encoding gene (PLB1) from C. neoformans and constructed plb1 mutants using targeted gene disruption. All three enzyme activities were markedly reduced in the mutants compared with the wild‐type parent. The plb1 strains did not have any defects in the known cryptococcal virulence phenotypes of growth at 37°C, capsule formation, laccase activity and urease activity. The plb1 strains were reconstituted using the wild‐type locus and this resulted in restoration of all extracellular PLB activities. In vivo testing demonstrated that the plb1 strain was significantly less virulent than the control strains in both the mouse inhalational model and the rabbit meningitis model. We also found that the plb1 strain exhibited a growth defect in a macrophage‐like cell line. These data demonstrate that secretory phospholipase is a virulence factor for C. neoformans.

Significance: Epidemics of microbial infections are a considerable threat to human and animal health. Analysis of 3,615 genome sequences, coupled with virulence studies in animals, permitted us to delineate the nature and timing of molecular events that contributed to an ongoing global human epidemic of infections caused by group A Streptococcus , the “flesh-eating” pathogen. We clarified decades-long uncertainty about the timing and sequence of genomic alterations that underpinned the global epidemic. Analyses of this type are crucial for developing better strategies to predict and monitor strain emergence and epidemics, formulate effective protective public health maneuvers, and develop or modify vaccines.

Key Points: Diverse patient groups with GATA2 mutation develop mononuclear cytopenia and elevated Flt3 ligand. Progressive cytopenias, rising Flt3 ligand, and terminal differentiation of lymphoid cells accompany clinical progression.

Background. Acute bacterial cellulitis is a potentially serious infection that commonly recurs. The identification of preventable risk factors could

Ingileif Jonsdottir, Kari Stefansson and colleagues show that variants in the HLA class II region contribute to tuberculosis risk in populations of European ancestry. They propose that the associated variants influence disease risk by altering expression of HLA class II molecules presenting protective M. tuberculosis antigens to T cells. Mycobacterium tuberculosis infections cause 9 million new tuberculosis cases and 1.5 million deaths annually1. To identify variants conferring risk of tuberculosis, we tested 28.3 million variants identified through whole-genome sequencing of 2,636 Icelanders for association with tuberculosis (8,162 cases and 277,643 controls), pulmonary tuberculosis (PTB) and M. tuberculosis infection. We found association of three variants in the region harboring genes encoding the class II human leukocyte antigens (HLAs): rs557011[T] (minor allele frequency (MAF) = 40.2%), associated with M. tuberculosis infection (odds ratio (OR) = 1.14, P = 3.1 × 10−13) and PTB (OR = 1.25, P = 5.8 × 10−12), and rs9271378[G] (MAF = 32.5%), associated with PTB (OR = 0.78, P = 2.5 × 10−12)—both located between HLA-DQA1 and HLA-DRB1—and a missense variant encoding p.Ala210Thr in HLA-DQA1 (MAF = 19.1%, rs9272785), associated with M. tuberculosis infection (P = 9.3 × 10−9, OR = 1.14). We replicated association of these variants with PTB in samples of European ancestry from Russia and Croatia (P < 5.9 × 10−4). These findings show that the HLA class II region contributes to genetic risk of tuberculosis, possibly through reduced presentation of protective M. tuberculosis antigens to T cells.

A nationwide study on candidemia was conducted in Iceland from 1980 to 1999. The annual incidence increased from 1.4 cases/100,000 inhabitants/year between 1980 and 1984 to 4.9 cases/100,000 inhabitants/year between 1995 and 1999 ( P < 0.0001). Candidemia episodes at university hospitals increased from 0.15/1,000 admissions to 0.55/1,000 admissions ( P < 0.0001). Candida albicans was the predominant species responsible (64.4%). The national import of fluconazole increased approximately fourfold during the second half of the study, but increased resistance to this agent was not observed.