Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans.

Candida albicans remains the most common species causing invasive candidiasis. In this study, we present the population structure of 551 global C. albicans strains. Of these, the antifungal susceptibilities of 370 strains were tested. Specifically, 66.6% of the azole-nonsusceptible (NS)/non-wild-type (NWT) strains that were tested belonged to Clade 1. A phylogenetic analysis, a principal components analysis, the population structure, and a loss of heterozygosity events revealed two nested subclades in Clade 1, namely, Clade 1-R and Clade 1-R-α, that exhibited higher azole-NS/NWT rates (75.0% and 100%, respectively). In contrast, 6.4% (21/326) of the non-Clade 1-R isolates were NS/NWT to at least 1 of 4 azoles. Notably, all of the Clade 1-R-α isolates were pan-azole-NS/NWT that carried unique A114S and Y257H double substitutions in Erg11p and had the overexpression of ABC-type efflux pumps introduced by the substitution A736V in transcript factor Tac1p. It is worth noting that the Clade 1-R and Clade 1-R-α isolates were from different cities that are distributed over a large geographic span. Our study demonstrated the presence of specific phylogenetic subclades that are associated with antifungal resistance among C. albicans Clade 1, which calls for public attention on the monitoring of the future spread of these clones. IMPORTANCE Invasive candidiasis is the most common human fungal disease among hospitalized patients, and Candida albicans is the predominant pathogen. Considering the large number of infected cases and the limited alternative therapies, the azole-resistance of C. albicans brings a huge clinical threat. Here, our study suggested that antifungal resistance in C. albicans could also be associated with phylogenetic lineages. Specifically, it was revealed that more than half of the azole-resistant C. albicans strains belonged to the same clade. Furthermore, two nested subclades of the clade exhibited extremely high azole-resistance. It is worth noting that the isolates of two subclades were from different cities that are distributed over a large geographic span in China. This indicates that the azole-resistant C. albicans subclades may develop into serious public health concerns.

[Epidemiological study of Streptococcus pneumoniae in the nasopharynx of healthy children under 5 years of age in Wuhan].

OBJECTIVE: To investigate the population biology of Streptococcus (S.) pneumoniae carried by healthy children under 5 years of age in Wuhan. METHODS: S. pneumoniae was isolated from nasopharyngeal swabs of healthy children under the age of 5 years (under 5) in Wuhan. The susceptibility to 12 antimicrobial agents was tested by agar dilution method. The erythromycin resistant genes were detected by using the technique of polymerase chain reaction. The quellung reaction was used for serotyping. RESULTS: The carrier rate of S. pneumoniae was 22.31% (135/605) in under 5 children in Wuhan. Among the 133 alive strains, the proportion of penicillin non-susceptible S. pneumoniae (PNSSP) was 45.9% (61/133). The susceptibility of S. pneumoniae to the first (cefalexin), the second (cefaclor) and the third (cefixime, cefpodoxime and cetriaxone) generations of cephalosporins was 6.0%, 45.1%, 54.9%, 56.4%, and 88.7%, respectively. None of the strains were found resistant to fluoroquinolones except for one strain which was resistant to ciprofloxacin at low level. The susceptibility to macrolides was low, 14.3% - 15.8%. Among totally 114 strains resistant to erythromycin, the genes ermB alone, both ermB and mefA, and mefA alone were found in 76 strains (66.7%), 46 strains (40.4%) and 2 strains (1.8%), respectively. Seventeen serotypes were involved and the prevalent serotypes were 19, 23, 6, 15 and 14. Seven strains remained nontypable for serotype. PNSSP strains were found to be distributed in serotypes 19, 23, 6 and nontypable group. CONCLUSIONS: The antibiotic resistance of S. pneumoniae was serious in Wuhan area. The ribosomal modification (ermB gene mediated) was the main mechanism of S. pneumoniae resistant to erythromycin. The major prevalent serotypes were 19, 23 and 6.

Lung endothelium targeting for pulmonary embolism thrombolysis.

BACKGROUND: Pulmonary embolism occurs frequently in hospitalized patients. Thrombolytic therapy, currently used as the major treatment, has often been associated with severe bleeding complications and has thereby been life-threatening. We have developed a novel therapeutic method based on our newly created pulmonary endothelium-specific antibody. METHODS AND RESULTS: We isolated membrane proteins of rat pulmonary vascular luminal endothelium and obtained a monoclonal antibody, RE8F5, which antigen was uniquely expressed by the pulmonary capillary endothelium. In vivo biodistribution showed that RE8F5 and its urokinase conjugate were rapidly and specifically accumulated in lung. Urokinase and the conjugate were compared in rats with pulmonary, hepatic, and lower-limb embolus. In a pulmonary embolus model, the conjugate exhibited 12-fold enhanced thrombolytic potency over urokinase, whereas plasma fibrinogen and bleeding time were unaffected. In 2 other models, no significant thrombolysis was induced by the conjugate. In contrast, thrombolysis by urokinase was found to be comparable to the pulmonary embolus model. In addition, urokinase caused significant consumption of fibrinogen in all experiments. CONCLUSIONS: These data show that urokinase equipped with lung endothelium-specific antibody is an ideal treatment for pulmonary embolism, with a high efficacy of thrombolysis and low risk of bleeding.