SUMMARY Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family in which four women who were affected by either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop-codon mutation Tyr238X in the β-glucan receptor dectin-1. The mutated form of dectin-1 was poorly expressed, did not mediate β-glucan binding, and led to defective production of cytokines (interleukin-17, tumor necrosis factor, and interleukin-6) after stimulation with β-glucan or Candida albicans. In contrast, fungal phagocytosis and fungal killing were normal in the patients, explaining why dectin-1 deficiency was not associated with invasive fungal infections and highlighting the specific role of dectin-1 in human mucosal antifungal defense.

Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed whole genome phylogeny from representative strains of both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis demonstrates that predicting phylogenetic structure using the ompA gene, traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks true relationships. We show that in many instances ompA is a chimera that can be exchanged in part or whole, both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, another important diagnostic target. We have used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.

Chlamydia trachomatis is the world's most prevalent bacterial sexually transmitted infection and leading infectious cause of blindness, yet it is one of the least understood human pathogens, in part due to the difficulties of in vitro culturing and the lack of available tools for genetic manipulation. Genome sequencing has reinvigorated this field, shedding light on the contemporary history of this pathogen. Here, we analyze 563 full genomes, 455 of which are novel, to show that the history of the species comprises two phases, and conclude that the currently circulating lineages are the result of evolution in different genomic ecotypes. Temporal analysis indicates these lineages have recently expanded in the space of thousands of years, rather than the millions of years as previously thought, a finding that dramatically changes our understanding of this pathogen's history. Finally, at a time when almost every pathogen is becoming increasingly resistant to antimicrobials, we show that there is no evidence of circulating genomic resistance in C. trachomatis.

The risk of developing late complications after chlamydia lower genital tract infection appears low. High quality RCTs dealing with the transition from cervicitis to infertility are needed to broaden the evidence. In screening programmes, chlamydia antibody testing, as an intermediate marker for potential adverse sequelae, might enable more precise estimates.

The natural course of asymptomatic Chlamydia trachomatis infections in women was studied during one year in a cohort based nested case-control study. Healthy women (n = 744, from four company health services in Amsterdam) with a medical check-up prior to job engagement were included. C. trachomatis-positive women (n = 30, cases) and a randomly selected control group of C. trachomatis-negative women (n = 186, controls) were followed for one year. Urine specimens (at one, six and 12 months) were analysed for the presence of C. trachomatis-DNA and the C. trachomatis-serovars, and questionnaires were filled in. The C. trachomatis prevalence and natural course in relation to demographic and sexual characteristics after one, six and 12 months were studied. The main outcome measures were 1) the prevalence of C. trachomatis using urine specimens; 2) self-reported complaints; 3) clinical symptoms reported to the coordinating physicians. The prevalence of asymptomatic C. trachomatis infections was 4% and there was no correlation with demographic and sexual characteristics. The person/year clearance rate was 44.7% per year. None of the C. trachomatis-positive women developed clinical symptoms or used C. trachomatis specific antibiotic treatment. Women with or without an asymptomatic infection had the same number of self-reported urogenital complaints during follow-up. In persisting infections twice as many C. trachomatis-serovar E infections were detected as compared to clearing infections. Our findings showed that almost half of the asymptomatic C. trachomatis infections in women cleared during one year of follow-up and none developed clinical pelvic inflammatory disease (PID), which is a much lower figure than previously suggested. Therefore these data are important for cost effectiveness calculations in screening programmes for asymptomatic C. trachomatis infections.

Background: The obligate intracellular growing bacterium Chlamydia trachomatis causes diseases like trachoma, urogenital infection and lymphogranuloma venereum with severe morbidity. Several serovars and genotypes have been identified, but these could not be linked to clinical disease or outcome. The related Chlamydophila pneumoniae, of which no subtypes are recognized, causes respiratory infections worldwide. We developed a multi locus sequence typing (MLST) scheme to understand the population genetic structure and diversity of these species and to evaluate the association between genotype and disease.

LGV testing is recommended for MSM with anorectal chlamydia. If routine LGV serovar typing is unavailable, we propose administration of syndromic LGV treatment for MSM with anorectal chlamydia and either proctitis detected by proctoscopic examination, > 10 white blood cells/high-power field detected on an anorectal smear specimen, or HIV seropositivity.

The large number of sexually transmitted diseases and ocular trachoma cases that are caused globally each year by Chlamydia trachomatis has made this organism a World Health Organization priority for vaccine development. However, there is no gene transfer system for Chlamydia to help identify potential vaccine targets. To accelerate discoveries toward this goal, here we analyzed the broadest diversity of C. trachomatis genomes to date, including 25 geographically dispersed clinical and seven reference strains representing 14 of the 19 known serotypes. Strikingly, all 32 genomes were found to have evidence of DNA acquisition by homologous recombination in their history. Four distinct clades were identified, which correspond to all C. trachomatis disease phenotypes: lymphogranuloma venereum (LGV; Clade 1); noninvasive urogenital infections (Clade 2); ocular trachoma (Clade 3); and protocolitis (Clade 4; also includes some noninvasive urogenital infections). Although the ancestral relationship between clades varied, most strains acted as donor and recipient of recombination with no evidence for barriers to genetic exchange. The niche-specific LGV and trachoma clades have undergone less recombination, although the opportunity for mixing with strains from other clades that infect the rectal and ocular mucosa, respectively, is evident. Furthermore, there are numerous occasions for gene conversion events through sequential infections at the same anatomic sites. The size of recombinant segments is relatively small (~357 bp) compared with in vitro experiments of various C. trachomatis strains but is consistent with in vitro estimates for other bacterial species including Escherichia coli and Helicobacter pylori. Selection has also played a crucial role during the diversification of the organism. Clade 2 had the lowest nonsynonymous to synonymous ratio (dN/dS) but the highest effect of recombination, which is consistent with the widespread occurrence of synonymous substitutions in recombined genomic segments. The trachoma Clade 3 had the highest dN/dS estimates, which may be caused by an increased effect of genetic drift from niche specialization and a reduced effective population size. The degree of drift, selection, and recombination in C. trachomatis suggests that the challenge will remain to identify genomic regions that are stable and cross protective for the development of an efficacious vaccine.