Staphylococcus aureus, or methicillin-resistant S. aureus (MRSA), is a significant pathogen in both nosocomial and community infections. Community-associated MRSA (CA-MRSA) strains tend to be multi-drug resistant and to invade hospital settings. This study aimed to assess the antimicrobial resistance and molecular characteristicsof nasal S. aureus among newlyadmitted inpatients.In the present study, 66 S. aureus isolates, including 10 healthcare-associated MRSA (HA-MRSA), 8 CA-MRSA, and 48 methicillin-sensitive S. aureus (MSSA) strains, were found in the nasal cavities of 62 patients by screening 292 newlyadmitted patients. Antimicrobial resistance and molecular characteristics of these isolates, including spa-type, sequence type (ST) and SCCmec type, were investigated. All isolates were sensitive to linezolid, teicoplanin, and quinupristin/dalfopristin, but high levels of resistance to penicillin and erythromycin were detected. According to D-test and erm gene detection results, the cMLSB and iMLSB phenotypes were detected in 24 and 16 isolates, respectively. All 10 HA-MRSA strains displayed the cMLSB phenotypemediated by ermA or ermA/ermC, while the cMLSB CA-MRSA and MSSA strains carried the ermB gene. Molecular characterization revealedall 10 HA-MRSA strains were derived from the ST239-SCCmec III clone, and four out of eight CA-MRSA strains were t437-ST59-SCCmec V. The results suggest that patients play an indispensable role in transmitting epidemic CA-MRSA and HA-MRSA strains.
Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/genetics ; Drug Resistance, Multiple, Bacterial/genetics ; Humans ; Inpatients ; Methicillin-Resistant Staphylococcus aureus/*drug effects/genetics/isolation & purification ; Methyltransferases/genetics ; Microbial Sensitivity Tests ; Nasal Cavity/*microbiology ; Staphylococcal Infections/diagnosis/microbiology ; Staphylococcus aureus/*drug effects/genetics/isolation & purification

Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c.163G>C (p.Val55Leu) mutation in FKBP5 (encodes FK506-binding protein 51, FKBP51) associated with PDB using whole-exome sequencing. Mutant FKBP51 enhanced the Akt phosphorylation and kinase activity in cells. A study of osteoclast function using FKBP51V55L KI transgenic mice proved that osteoclast precursors from FKBP51V55L mice were hyperresponsive to RANKL, and osteoclasts derived from FKBP51V55L mice displayed more intensive bone resorbing activity than did FKBP51WT controls. The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. However, c-fos expression showed no significant difference in the wild-type and mutant groups. Akt phosphorylation in FKBP51V55L BMMs was elevated in response to RANKL. In contrast, IκB degradation, ERK phosphorylation and LC3II expression showed no difference in wild-type and mutant BMMs. Micro-CT analysis revealed an intensive trabecular bone resorption pattern in FKBP51V55L mice, and suspicious osteolytic bone lesions were noted in three-dimensional reconstruction of distal femurs from mutant mice. These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.
Acid Phosphatase ; Animals ; Asian Continental Ancestry Group ; Bone Diseases, Metabolic ; Bone Remodeling ; Bone Resorption ; Femur ; Humans ; Mice ; Mice, Transgenic ; Osteitis Deformans* ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Phosphorylation ; Phosphotransferases ; Tacrolimus Binding Proteins ; Transcription Factors