Highlights d scRNA-seq identifies four epidermal basal cell states in homeostatic adult skin d Computational analysis supports a ''hierarchical'' model of epidermal homeostasis d Basal cell states are metabolically distinct and spatially partitioned in wounded skin d Epidermal basal cells show enhanced cell fate and state plasticity during wound healing
i Azole resistance in Aspergillus fumigatus has emerged as a worldwide public health problem. We sought here to demonstrate the occurrence and characteristics of azole resistance in A. fumigatus from different parts of China. A total of 317 clinical and 144 environmental A. fumigatus isolates from 12 provinces were collected and subjected to screening for azole resistance. Antifungal susceptibility, cyp51A gene sequencing, and genotyping were carried out for all suspected azole-resistant isolates and a subset of azole-susceptible isolates. As a result, 8 (2.5%) clinical and 2 (1.4%) environmental A. fumigatus isolates were identified as azole resistant. Five azole-resistant strains exhibit the TR 34 /L98H mutation, whereas four carry the TR 34 /L98H/S297T/F495I mutation in the cyp51A gene. Genetic typing and phylogenetic analysis showed that there was a worldwide clonal expansion of the TR 34 / L98H isolates, while the TR 34 /L98H/S297T/F495I isolates from China harbored a distinct genetic background with resistant isolates from other countries. High polymorphisms existed in the cyp51A gene that produced amino acid changes among azolesusceptible A. fumigatus isolates, with N248K being the most common mutation. These data suggest that the wide distribution of azole-resistant A. fumigatus might be attributed to the environmental resistance mechanisms in China.
Highlights d scRNA-seq identifies four epidermal basal cell states in homeostatic adult skin d Computational analysis supports a ''hierarchical'' model of epidermal homeostasis d Basal cell states are metabolically distinct and spatially partitioned in wounded skin d Epidermal basal cells show enhanced cell fate and state plasticity during wound healing
The use of azole fungicides in agriculture is believed to be one of the main reasons for the emergence of azole resistance in Though widely used in agriculture, imidazole fungicides have not been linked to resistance in This study showed that elevated MIC values of imidazole drugs were observed against isolates with TR/L98H/S297T/F495I mutation, but not among isolates with TR/L98H mutation. Short-tandem-repeat (STR) typing analysis of 580 isolates from 20 countries suggested that the majority of TR/L98H/S297T/F495I strains from China were genetically different from the predominant major clade comprising most of the azole-resistant strains and the strains with the same mutation from the Netherlands and Denmark. Alignments of sterol 14α-demethylase sequences suggested that F495I in was orthologous to F506I in and F489L in , which have been reported to be associated with imidazole resistance. antifungal susceptibility testing of different recombinants with mutations further confirmed the association of the F495I mutation with imidazole resistance. In conclusion, this study suggested that environmental use of imidazole fungicides might confer selection pressure for the emergence of azole resistance in.
Staphylococcus aureus belongs to one of the most common bacteria causing healthcare and community associated infections in China, but their molecular characterization has not been well studied. From May 2011 to June 2012, a total of 322 non-duplicate S. aureus isolates were consecutively collected from seven tertiary care hospitals in seven cities with distinct geographical locations in China, including 171 methicillin sensitive S. aureus (MSSA) and 151 MRSA isolates. All isolates were characterized by spa typing. The presence of virulence genes was tested by PCR. MRSA were further characterized by SCCmec typing. Seventy four and 16 spa types were identified among 168 MSSA and 150 MRSA, respectively. One spa type t030 accounted for 80.1% of all MRSA isolates, which was higher than previously reported, while spa-t037 accounted for only 4.0% of all MRSA isolates. The first six spa types (t309, t189, t034, t377, t078 and t091) accounted for about one third of all MSSA isolates. 121 of 151 MRSA isolates (80.1%) were identified as SCCmec type III. pvl gene was found in 32 MSSA (18.7%) and 5 MRSA (3.3%) isolates, with ST22-MSSA-t309 as the most commonly identified strain. Compared with non-epidemic MRSA clones, epidemic MRSA clones (corresponding to ST239) exhibited a lower susceptibility to rifampin, ciprofloxacin, gentamicin and trimethoprim-sulfamethoxazole, a higher prevalence of sea gene and a lower prevalence of seb, sec, seg, sei and tst genes. The increasing prevalence of multidrug resistant spa-t030 MRSA represents a major public health problem in China.
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