Zhongyi Lu

Characterization of Staphylococcus aureus from distinct geographic locations in China: an increasing prevalence of spa-t030 and SCCmec type III.

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.

Epidemiology and Molecular Characterizations of Azole Resistance in Clinical and Environmental Aspergillus fumigatus Isolates from China.

ABSTRACT 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 TR34/L98H mutation, whereas four carry the TR34/L98H/S297T/F495I mutation in the cyp51A gene. Genetic typing and phylogenetic analysis showed that there was a worldwide clonal expansion of the TR34/L98H isolates, while the TR34/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 azole-susceptible 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.

Emergence of TR46/Y121F/T289A in an Aspergillus fumigatus Isolate from a Chinese Patient.

Azole resistance in Aspergillus fumigatus is increasingly reported and evolving into a global health problem (1).…

Role of the small GTPase Rho1 in cell wall integrity, stress response, and pathogenesis of Aspergillus fumigatus

Aspergillus fumigatus is a major pathogen of invasive pulmonary aspergillosis. The small GTPase, Rho1, of A. fumigatus is reported to comprise a potential regulatory subunit of β-1,3-glucan synthase and is indispensable for fungal viability; however, the role of AfRho1 on the growth, cell wall integrity, and pathogenesis of A. fumigatus is still poorly understood. We constructed A. fumigatus mutants with conditional- and overexpression of Rho1 and found that defects of AfRho1 expression led to the reduction of β-1,3-glucan and glucosamine moieties on the cell wall, with down-regulated transcription of genes in the cell wall integrity signaling pathway and a decrease of calcofluor white (CFW)-stimulated mitogen-activated protein kinase (MpkA) phosphorylation and cytoplasmic leakage compared to those of the wild-type strain (WT). In addition, down-regulation of AfRho1 expression caused much higher sensitivity of A. fumigatus to H2O2 and alkaline pH compared to that of WT. Decrease of AfRho1 expression also attenuated the A. fumigatus pathogenicity in Galleria mellonella and inhibited conidial internalization into lung epithelial cells and inflammatory factor release. In contrast, overexpression of Rho1 did not alter A. fumigatus morphology, susceptibility to cell wall stresses, or pathogenicity relative to its parental strain. Taken together, our findings support AfRho1 as an essential regulator of the cell wall integrity, stress response, and pathogenesis of A. fumigatus.

Assessing antibiotic therapy effectiveness against the major bacterial pathogens in a hospital using an integrated index

AIM To assess the effectiveness of antibiotic therapy against five indicator bacteria in a Chinese hospital using an index-based approach. METHODS The study population comprises 1031 patients who had one clinically significant bacterial isolate in 2008, 2010 and 2013. Drug resistance index (DRI) based on pathogens was calculated. RESULTS The adaptive DRIs for Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus decreased, while both adaptive and fixed DRIs for Acinetobacter spp. increased from 2008 to 2013. The adaptive DRIs for Escherichia coli increased from 2008 to 2013, while the fixed DRIs exhibited a decreasing trend. CONCLUSION DRI could be used to demonstrate the changes of antimicrobial resistance and prescribing over time as a result of evolutionary processes and governmental regulatory interference.