To investigate a potential impact of interleukin 22 (IL-22) gene polymorphisms on susceptibility to pulmonary tuberculosis (PTB) in a Chinese population, a case-control study was conducted in PTB cases (n=453), latent tuberculosis infection (LTBI) cases (n=109) and healthy controls (HCs) (n=264). Genetic polymorphisms of rs1179249, rs2227491, rs17224704, rs2227478 were analyzed by using SNPscan™ technique. The genetic frequencies of four single nucleotide polymorphisms (SNPs) met Hardy-Weinberg equilibrium. In the population older than 55, the frequency of genotype TA of rs17224704 SNP was significantly higher in healthy control group than that in PTB group (P=0.047 9,OR=0.365,95% CI=0.135-0.991). The frequency of genotype AA of rs17224704 SNP was significantly lower in LTBI group than that in PTB group (P=0.027 6). The frequency of genotype TA of rs17224704 SNP was significantly higher in LTBI group than that in PTB group (P=0.007 37, OR=0.213,95% CI=0.069-0.660). The frequency of allele T of rs17224704 SNP was significantly higher in healthy control group and LTBI group than that in PTB group (P=0.026 9, OR=0.388, 95% CI=0.167-0.897; P=0.025 0, OR=0.322, 95% CI=0.119-0.867). The results suggest that allele T of rs17224704 gene in Chinese Han population from Chongqing is probably associated with protection against tuberculosis.
Four-stranded helical structures called G-quadruplexes (G4s) formed by G-rich DNA sequences are non-canonical structures. G4s are now known to affect gene expression and genome stability. Studies have suggested that Mycobacterium tuberculosis (M. tuberculosis) espK is an important component of ESX-1 (ESAT-6 secretion system-1), and its protein sequence has tandem repetitive GTPITP sequence polymorphism. In this study, we identified a G4 sequence of espK (Rv3879c) on the template strand corresponding to GTPITP sequence polymorphism region, and this G4 sequence only existed in M. tuberculosis complex (MTBC). By comparing espK gene nucleic acid sequence in the clinical M. tuberculosis isolates, we confirmed a high-frequency G4 single nucleotide polymorphism (SNP), G1573C mutation in espK gene. The purpose of the study is to analyze the structure and expression regulation of espK G4. Firstly, espK G4 nucleic acid fragment in vitro could form parallel G4 structure in the presence of K+ by circular dichroism spectrum detection and the structural stability of G4 decreased after synonymous point mutation of G4. We constructed espK expression plasmid containing synonymous point mutant G4 by overlapping polymerase chain reaction (PCR), and further constructed recombinant strains with espK gene of synonymous point mutant G4 and wild-type espK. By quantitative real-time PCR detection, transcription level of recombinant strains with espK gene of synonymous point mutant G4 was significantly upregulated (P<0.05). At the same time, the high-frequency G1573C mutant in espK could destabilize G4 structure and resulted in increased protein expression level in the recombinant strain by Western blotting. It is thus concluded that G4 of M. tuberculosis espK could regulate expression, and the sequence polymorphism in espK G4 region may regulate the activity of ESX-1 secretion system through affecting the expression level of EspK.
The present paper aims to analyze the pathogen spectrum of hand, foot and mouth disease (HFMD) and epidemic dynamics of main pathogens in Shanghai from 2011 to 2016. The samples were collected from children diagnosed with HFMD in sentinel hospitals from 2011 to 2016. General and classified tests for enteroviruses were carried out, and the biological characteristics of both recombined and non-recombined coxsackievirus A6 (CA6) strains were analyzed. It was found that the main pathogens of HFMD were enterovirus type 71 (EV71) and CA16 from 2011 to 2012 in Shanghai area, and CA6 became the main pathogen in the autumn of 2012. From 2013 to 2014, recombined CA6 (R CA6) occupied a certain proportion, but non-recombined CA6 (NR CA6) became dominant during 2015—2016. R CA6 and NR CA6 were highly proliferative in human rhabdomyoma cells (RD cells) but had no obvious proliferation in human oral epidermoid carcinoma cells (KB cells), human embryo lung cells (MRC-5 cells) and human laryngeal epidermoid carcinoma cells (HEp-2 cells). The results confirmed that CA6 was the major causative agent of HFMD in Shanghai in recent years. Both R CA6 and NR CA6 strains could infect RD cells. The detection ratio of R CA6 and NR CA6 changed year by year. These results indicate that monitoring and characterizing the main pathogens of HFMD continuously was a critical step for the prevention of HFMD and vaccine development.
Acinetobacter baumannii (A. baumannii) is the major pathogen causing nosocomial infectious diseases in the world due to various intrinsic and acquired mechanisms of drug resistance. There are no effective treatments for the infections caused by multidrug-resistant A. baumannii and extensively-resistant A. baumannii. This review lists standard drugs and new options for the treatment.
Sepsis is a life-threatening infection demanding accurate and fast diagnosis of pathogen for right antibiotics. In current practice, culture-based methods are still the standard approach of etiological diagnosis of sepsis. Practically, these methods have disadvantages including long turnaround time and low sensitivity. Although molecular assays, such as polymerase chain reaction (PCR)-based methods have been established for sepsis, the spectrum of the detection is limited to known pathogens listed on the panel. In the last few years, the next-generation sequencing (NGS) has been constantly improving and stepped into clinical practice, providing a powerful tool with advantages including short turnaround time, full spectrum and semiquantitative analysis. Although NGS has clear advantages compared with culture-based methods, we are facing the following challenges: few acknowledged criteria of sequencing result explanation have been established; the relationship between sequencing results and treatment effects is undetermined; and the drug resistance gene detection is usually with low sensitivity. Besides, large-scale study comparing NGS with traditional etiological diagnosis methods is missing. Thus, NGS still needs high-level evidence to support its clinical application.
Mitophagy is a special version of autophagy which eliminates damaged or redundant mitochondria effectively and selectively. Eukaryotes conduct mitochondrial quality control via mitophagy to maintain the function of the power-generating organelles. Recently, a series of studies have demonstrated that two Parkinson’s disease-related genes, PINK1 and parkin, were involved in mitophagy. Parkin and PINK1 cooperate with each other to recognize damaged mitochondria specifically. Particularly, ubiquitin and deubiquitinases play essential roles in modulating parkin activity and mitophagy efficiency. Here we introduce and review the recent studies on PINK1/parkin pathway in mitophagy.
Acinetobacter baumannii, a non-fermentative Gram-negative bacterium, is known for its antibiotic resistance and clone transmission. A precise and effective genotyping method for Acinetobacter baumannii is essential to conduct epidemiological studies and control infections. The article reviews the recent progress on genotyping methods of Acinetobacter baumannii, and discusses the basic principles, advantages, limitations and application scope of these methods.
Rcs is a complex two-component system in Enterobacteriaceae bacteria. It regulates the synthesis of bacterial colanic acids, and the expressions of bacterial flagella genes and resistance genes. Distinguished with typical two-component systems, Rcs consists of three components, among which phosphate group is transferred via three steps. Rcs in different species may possess its own distinct functions, mainly in the regulation of bacterial virulence and stress control. This review focuses on the components, function and signal transduction mechanisms of Rcs system.
Microbial communities with complex structure are colonized in human body, hosting interactions between fungi and bacteria. Early studies have focused mainly on a single species of bacteria or fungi, and recent studies have shown the interactions between bacteria and fungi are critical to study human microecosystems. Candida albicans is the most common opportunistic pathogenic fungus for human and is generally considered to be part of the normal human flora. The interactions between Candida albicans and bacteria, especially their synergistic and antagonistic effects on the balance between different species, have attracted more attentions in recent years. This paper reviews the mechanism of interactions between Candida albicans and bacteria and their impacts on human diseases.