A chromosome-encoded T4SS independently contributes to horizontal gene transfer in Enterococcus faecalis.

Bacterial type IV secretion systems (T4SSs) are the specific devices that mediate the dissemination of antibiotic resistant genes via horizontal gene transfer (HGT). Multi-drug-resistant Enterococcus faecalis (E. faecalis) represents a clinical public health threat because of its transferable plasmid with a functional plasmid-encoded (PE)-T4SS. Here, we report a chromosome-encoded (CE)-T4SS that exists in 40% of E. faecalis isolates. Compared with the PE-T4SS, CE-T4SS displays distinct characteristics in protein architecture and is capable of mediating large and genome-wide gene transfer in an imprecise manner. Reciprocal exchange of CE-T4SS- or PE-T4SS-associated origin of transfer (oriT) could disrupt HGT function, indicating that CE-T4SS is an independent system compared with PE-T4SS. Taken together, the CE-T4SS sheds light on the knowledge of HGT in gram-positive bacteria and triggers us to explore more evolutionary mechanisms in E. faecalis.

Recombination and mutation shape variations in the major histocompatibility complex.

The major histocompatibility complex (MHC) is closely associated with numerous diseases, but its high degree of polymorphism complicates the discovery of disease-associated variants. In principle, recombination and de novo mutations are two critical factors responsible for MHC polymorphisms. However, direct evidence for this hypothesis is lacking. Here, we report the generation of fine-scale MHC recombination and de novo mutation maps of ∼5 Mb by deep sequencing (> 100×) of the MHC genome for 17 MHC recombination and 30 non-recombination Han Chinese families (a total of 190 individuals). Recombination hotspots and Han-specific breakpoints are located in close proximity at haplotype block boundaries. The average MHC de novo mutation rate is higher than the genome-wide de novo mutation rate, particularly in MHC recombinant individuals. Notably, mutation and recombination generated polymorphisms are located within and outside linkage disequilibrium regions of the MHC, respectively, and evolution of the MHC locus was mainly controlled by positive selection. These findings provide insights on the evolutionary causes of the MHC diversity and may facilitate the identification of disease-associated genetic variants.

The emergence of multi-resistant Enterococcus faecalis clonal complex, CC4, causing nosocomial infections.

PURPOSE: Enterococcus faecalis is commonly found as a commensal gut bacteria, but some linages have caused increasing extra-gastrointestinal infections. In particular, strains with high-level virulence or antimicrobial resistance are prevalent in healthcare settings as nosocomial pathogens. This study was performed to elucidate the epidemiological characteristics and antimicrobial susceptibility profiles of E. faecalis causing nosocomial infections in a Chinese general hospital over a 4-year period. METHODOLOGY: We collected 77 isolates causing extra-gastrointestinal infections from patients at 14 different wards in a tertiary hospital from 2011 to 2014. The population relationship was assessed by multilocus sequence typing and multilocus variable-number tandem repeat analysis. The Kirby-Bauer disk diffusion method was used to evaluate susceptibility against 11 antimicrobial agents. RESULTS: The isolates showed high-level resistance to tetracycline (86.5 %), erythromycin (78.4 %), rifampin (62.2 %), etc. The major clonal complexes (CCs) included CC4, CC16 and CC21. As the most dominant subtype, CC16 was identified in almost all of the wards and all types of samples, but the isolation rate decreased continually. In contrast, the isolation rates of CC4 and CC21 increased and the proportion of these two CCs in 2014 was more than three times that in 2011. In addition, CC4 showed higher resistance than CC16. CONCLUSIONS: This study demonstrated the prevalent subtypes and resistance profiles of E. faecalis causing nosocomial infection, and indicated that CC4 may be a newly emerging high-risk, multi-resistant cluster. More surveillance is urgently needed, which will increase our understanding of the prevention and treatment of such infections.

A complex role of anthrax toxin receptor 2 polymorphisms and capillary morphogenesis protein 2 in ankylosing spondylitis pathogenesis.

This study investigated the role of anthrax toxin receptor 2 (ANTXR2) gene polymorphisms and capillary morphogenesis protein 2 (CMG2) expression in susceptibility and pathogenesis to ankylosing spondylitis (AS) in the Han Chinese in Beijing. A case-control study was performed using 602 AS patient samples meeting the revised New York criterion and 619 matched controls from Han Chinese individuals. Nineteen single-nucleotide polymorphisms (SNPs) of ANTXR2 genes were selected and genotyped using the Sequenom iPlex platform. Real-time polymerase chain reaction and flow cytometry were performed to investigate the impact of SNP polymorphisms on ANTXR2 transcription and CMG2 expression, respectively. The association of variants with AS was examined with UNPHASED 3.1.5. A novel association was observed between AS and three SNPs in the ANTXR2 gene (rs4690127, rs6823031, and rs4333130; P = 0.004, 0.011, and 0.013, respectively), confirming the association between rs433130 and AS in the Han Chinese. The strongest haplotype association was observed with rs4690127-rs6823031-rs4333130 (P = 2.5 × 10(-4)). rs6534639 and rs4333130 showed a cis-interaction (P = 0.027) in AS. ANTXR2 messenger RNA (mRNA) expression was significantly higher in the AS group than in the control group (P = 0.039). CMG2 expression in the lipopolysaccharide (LPS)-stimulated group was significantly lower than that in the control group (P = 0.018). This study reports a novel association between ANTXR2 and AS in the Han Chinese. ANTXR2 genetic polymorphisms affect ANTXR2 mRNA transcription and CMG2 expression. The opposing results observed for ANTXR2 transcription and CMG2 expression suggest a complex role of ANTXR2 polymorphisms in AS pathogenesis.