Abstract:Antibiotics are critical weapons that were used for combating human pathogens. However, the heavy use of antibiotics leads to the increased and widely spread of antimicrobial resistance. The antimicrobial resistance is not only a medical problem, but also social and economic concerns, involving public health, environmental pollution, food safety, etc. This special issue reviewed and discussed the recent progress on antimicrobial resistance regarding the fields of clinical drug resistance and epidemiology, animal and environmental drug resistance, drug resistance mechanisms, antimicrobial drug development and drug resistance prevention and control, hoping to give a comprehensive view on basic antimicrobial resistance questions, future research directions and prevention and control strategies.

Abstract:To dynamically investigate the distribution and antimicrobial resistance profiles of bacteremia pathogens isolated from different regions in China in 2011, 2013 and 2016. Non-repetitive isolates from nosocomial bloodstream infections were retrospectively collected and detected for antimicrobial susceptibility tests (AST) by agar dilution or microbroth dilution methods. Whonet 5.6 was used to analyze the AST data. Among 2 248 isolates, 1 657 (73.7%) were Gram-negative bacilli and 591 (26.3%) were Gram-positive cocci. The top five bacteremia pathogens were as follows, Escherichia coli (32.6%, 733/2 248), Klebsiella pneumoniae (14.5%, 327/2 248), Staphylococcus aureus (10.0%, 225/2 248), Acinetobacter baumannii (8.7%, 196/2 248) and Pseudomonas aeruginosa (6.2%, 140/2 248). Colistin (96.5%, 1 525/1 581, excluding innate resistant organisms), tigecycline (95.6%, 1 375/1 438, excluding innate resistant organisms), ceftazidine/clavulanate acid (89.2%, 1 112 /1 246), amikacin (86.4%, 1 382/1 599) and meropenem (85.7%, 1 376/1 605) showed relatively high susceptibility against Gram-negative bacilli. While tigecycline, teicoplanin and daptomycin (the susceptibility rates were 100.0%), vancomycin and linezolid (the susceptibility rates were 99.7%) demonstrated high susceptibility against Gram-positive cocci. The prevalence of extended-spectrum β-lactamases (ESBLs)-producing Enterobacteriaceae were 50.6% (206/407), 49.8% (136/273) and 38.9% (167/429) in 2011, 2013 and 2016 respectively; carbapenem-non-susceptible Enterobacteriaceae were 2.2% (9/408), 4.0% (16/402) and 3.9% (17/439) in 2011, 2013 and 2016 respectively; The prevalence of multidrug-resistant A. baumannii (MDRA) was 76.4% (55/72) in 2011, 82.7% (43/52) in 2013 and 87.5% (63/72) in 2016, respectively. The prevalence of multidrug-resistant P. aeruginosa (MDRP) was 9.8% (5/51) in 2011, 20.0% (7/35) in 2013 and 13.0% (7/54) in 2016, respectively. The prevalence of methicillin-resistant S. aureus (MRSA) was 51.9% (41/79) in 2011, 29.7% (19/64) in 2013 and 31.7% (26/82) in 2016, respectively. The prevalence of high level gentamicin resistance (HLGR) of Enterococcus faecium and Enterococcus faecalis were 43.2% (48/111) and 40.9% (27/66), respectively. The predominant organism of carbapenem-non-susceptible Enterobacteriaceae was K. pneumoniae with its proportion of 57.1% (24/42). Among 30 tigecycline-non-susceptible Enterobacteriaceae, K. pneumoniae was the most popular organism with 76.7% (23/30). Among 39 colistin-resistant Enterobacteriaceae, E. coli, Enterobacter cloacae and K. pneumoniae were constituted with the percent of 43.6 (17/39), 35.9 (14/39) and 15.4 (6/39), respectively. The Gram-negative bacilli (E. coli and K. pneumoniae were the major organisms) were the major pathogens of nosocomial bacteremia, to which tigecycline, colistin and carbapenems kept with highly in vitro susceptibility. Whereas, among the Gram-positive cocci, S. aureus was the top 1 isolated organism, followed by E. faecium, to which tigecycline, daptomycin, linezolid, vancomycin and teicoplanin kept with highly in vitro susceptibility. Isolation of colistin-resistant Enterobacteriaceae, tigecycline-non-susceptible Enterobacteriaceae, linezolid- or vancomycin-non-susceptible Gram-positive cocci suggests more attention should be paid to these resistant organisms and dynamic surveillance was essential.

Abstract:To investigate the resistance mechanisms of tigecycline-non-susceptible Acinetobacter baumannii and for providing the evidence of the control of nosocomial infection and rational use of antibiotics. The minimum inhibitory concentrations (MICs) of 94 non repetitive tigecycline-non-susceptible A. baumannii from 20 hospitals in 12 cities of China were determined by agar dilution method and broth microdilution method. The molecular epidemiology was studied by Multilocus sequence typing (MLST) and eBURST software. PCR and sequencing techniques were used to analyze the resistance genes (blaOXA-40-like, blaOXA-58-like, blaOXA-23-like, blaOXA-51-like, blaNDM-1), ISAba1, and the mutation sites of adeR, adeS, and trm. The activity of polymyxin B and minocyclinem against tigecycline-non-susceptible A. baumannii were 100% and 25.5%, respectively. The sensitivities of other antibiotics were less than 3.5%, and the sensitivities of imipenem and meropenem totigecycline-non- susceptible A. baumannii were only 1.1%. A total of 12 ST types were identified, including ST195 (45, 47.9%), ST208 (19, 20.2%) and ST457 (10, 10.6%). EBURST analysis found that 8 of the ST types belonged to the clone complex 92 (Clonal Complex 92, CC92). The blaOXA-23-like type carbapenem gene was identiefied in 93 strains (99% positive); and none of the strains contained the blaNDM-1 gene. The detection rates of adeR and adeS were 73.4% and 91.5% respectively and high frequency mutation sites were located in adeR (Asp26Asn) and adeS (Ala97Glu); The ISAba1 located upstream of the adeS gene was detected in 12 strains of A. baumannii, mainly from the northern region of China. The 240 nucleotide deletion of the trm gene caused a frameshift leading to a premature stop. So the tigecycline-non-susceptible A. baumannii showed high resistance against most antibiotics except polymyxin B. The deletion and mutation of adeR, adeS and trm were the main resistant mechanisms in tigecycline-non-susceptible A. baumannii in China.

Abstract:Overuse of antibiotics in livestock farming has enriched antibiotic-resistant genes as well as resistant bacteria in farm animals and their related environments. These antibiotic-resistant genes can spread to the natural environments by horizontal gene transfer and even to the food chain, posing a serious threat to the ecological environment, food safety and human health. With the development of genomic technology, the diversity and ecological distribution of antibiotic-resistant genes in farm animals and their related environments have been recently revealed. Here we summarized the research progress on antibiotic resistance genes in related fields, potential influence on human health, and future research needs.

Abstract:World Health Organization has recognized antibiotic resistance is one of the serious threats to public health and food-safety in the 21st century. Recently, the antibiotic resistance gene (ARG) has been widely considered as a new pollutant. Now, many studies suggested that animal farm is one of the major reservoirs of ARGs. Antibiotic resistance bacteria and antibiotic resistance genes enter the environment along with animal excrement, accelerating the spread of ARGs in the environment. In the livestock and poultry breeding environment, ARGs and antibiotic resistant bacteria could be transmitted to humans through the food chain, water or air, posing a great threat to public health. This review highlights the prevalence of antibiotic resistant bacteria and antibiotic resistant genes in livestock-breeding environment, the retention and spread of ARGs and the method used to study the antibiotic resistance, which will provide certain support for risk assessment of antimicrobial resistance in food animal breeding environment.

Abstract:Antimicrobial resistance is a common problem in both veterinary and human medicine. The increasing incidence of multi-drug resistance and even pan-drug resistance is posing serious threat to public health and food safety. This review aimed to present an updated overview on antimicrobial resistance, covering the transmission mechanisms and its potential controlling strategies.

Abstract:Overuse of antibiotics in aquaculture, husbandry and healthcare has led to antibiotics residues in the enviuronment and the generation of antibiotic resistant bacteria that can be transferred into the human gut through food chain. Based on literatures, we reviewed the influence of bacterial resistance on intestinal flora and related immune regulation. Taking the source of antibiotic resistance to human intestinal flora as an entry point, we addressed the structure of human intestinal flora and the composition of drug resistance genes after exposure to pollutants. Moreover, we discussed the relationship among changes of intestinal flora, antibiotic resistance genes and immunomodulation related diseases. Last, we also indicated future research needs.

Abstract:TA (Toxin-Antitoxin) systems are widely spread in chromosomes and plasmids of bacteria and archaea. These systems consist of two co-expression genes, encoding stable toxin and sensitive antitoxin, respectively. The toxicity of toxins usually inhibits bacterial growth and antitoxins can neutralize the toxins. Interaction between them would regulate the growth state of bacteria precisely. According to the composition of TA and nature of antitoxin, six types of TA have been found. The role of these TA systems in bacteria has been a hot research topic in recent years. Now, the research status on functions of bacterial TA is reviewed.

Abstract:Currently, there are many studies on the mechanism of antibiotic resistance in Mycobacterium tuberculosis (Mtb), but there are few studies on its regulatory mechanism. Post-translational modifications (PTMs) have been recognized for their important role in controlling cellular dynamics such as metabolism and stress response, but the relationship between PTMs and antibiotic resistance gradually attracted the attention of researchers. Here, we summarize the definition of PTMs, and the mechanisms of antibiotic resistance in M. tuberculosis and discuss how PTMs are involved in antibiotic resistance, in order to provide a new breakthrough for the development of new anti-Ttb drugs.

Abstract:Beta-lactams are the most widely used antibiotics. One of the principle mechanisms for Gram-negative bacteria to resist β-lactams is by producing β-lactamases that degrade β-lactams. This review highlights two regulatory mechanisms for inducing β-lactamase in Gram-negative bacteria. In the ampR-ampC paradigm, the induction of β-lactamase is intimately linked to peptidoglycan recycling. AmpR, a LysR-type transcriptional regulator, plays a central role in regulating expression of β-lactamase. Recent studies found that two-component signal transduction pathway is activated by β-lactams, which in turn induces the expression of β-lactamase. Finally, we discussed the future research directions in β-lactam resistance in Gram-negative bacteria.

Abstract:Horizontal gene transfer contributes to the spread of antibiotic-resistance cassettes, the distribution of toxin-encoding phages and the transfer of pathogenicity islands. Natural transformation, which is the process of competent cells to uptake free DNA from environment and to recombine this DNA into the chromosome, is a mode of horizontal gene transfer. Natural transformation promotes the spread of antibiotic-resistance cassettes among different bacteria, resulting in the emergence of antibiotic resistant bacteria. The emergence of antibiotic resistant pathogens poses an enormous threat to the treatment of infections. Natural transformation could occur in many bacteria, but the mechanism many be different in different bacteria. Also, the inducer and efficiency of natural transformation in different bacteria are influenced by various factors. This review focuses on the mechanism and influencing factors of natural transformation in bacteria.

Abstract:Tuberculosis (TB), caused by Mycobacterium tuberculosis, has become a major human infectious disease. The existing first-line and second-line TB drugs have poor treatment outcomes in patients with MDR-TB and XDR-TB. There is an urgent need for new and better drugs to treat tuberculosis due to lengthy and complex treatment regimens and a rising problem of drug resistance. Microbial-derived natural products have revealed enormous reservoirs of as yet untapped lead compounds. In this review, we discuss the strategies that have been developed in bacteria and fungi to isolation of non-culturable microorganisms and activation of silent biosynthetic gene clusters involved in the study of microbial-derived natural products. This review also highlights recent advances in microbial-derived natural products with anti-tuberculosis activity using these methods.

Abstract:With the emergence and globally spread of drug-resistant bacteria, the discovery and development of new antibacterial drugs is imminent. The symbiotic bacteria distributed in different parts of the body can produce a variety of antibacterial molecules to inhibit the colonization and infection of pathogenic bacteria. Human symbiotic bacteria provide a potential treasure house of resource for the research and development of new drugs with broad new molecular structures and action mechanism. With the further development of bioinformatics tools, synthetic biology and omics technology such as genomics, the mining of human symbiotic bacteria antibacterial molecules will be more in-depth and provide an effective way to solve the problem of drug resistance. Here, we review the antimicrobial molecules produced by human symbiotic bacteria and introduce several methods to explore the resources of natural antibacterial drugs. With the development of modern biotechnology, the antimicrobial molecules of human symbiotic bacteria will be more comprehensively and systematically explored and applied.

Abstract:There is an urgent need to discover new anti-tuberculosis compounds with novel mechanisms of action in order to deal with tuberculosis and drug-resistant tuberculosis. In this article, the feature of several promising novel compounds with potential anti-tuberculosis activities is summarized, focusing on the drug targets of these compounds. These summaries will contribute to the further development of anti-tuberculosis drugs.

Abstract:Carbapenem-resistant Enterobacteriaceae (CRE) is rising rapidly all over the world, and challenges clinical diagnosis and treatment by various genotypes. This paper summarizes the characteristics and diagnostic methods of CRE. CRE can be divided into three categories and five families with various characteristics and resistant genes. The diagnosis method include the Kirby-Bauer screening test, double disc synergetic inhibition test with carbapenems collaboration (double disc EDTA and meropenem, phenylboronic acid and meropenem), modified Hodge test, chromogenic medium detection for selected test of CRE, and Carba NP colorimetric test, PCR and sequencing for CRE confirmation test. Each method has its own advantages and disadvantages, and can be applied according to the local main popular CRE genetypes and experimental conditions.

Abstract:Antimicrobial resistance is on the rise while the number of antibiotics being brought to market continues to drop. Drug-resistant genes and drug-resistant bacteria infection have seriously threatened human health. Therefore, antimicrobial resistance presents an ongoing challenge that requires multifaceted approaches including: biomedical innovation; improved surveillance of antibiotic consumption and antimicrobial resistance generated rates; prevention of health-care-associated infections and transmission of multidrug-resistant bacteria and environmental dissemination; rapid microbiological diagnosis; and curtailed clinical and veterinary misuse. Fortunately, combating antimicrobial resistance has been highly valued and supported by the government, scientists and entrepreneurs of various countries. With the continuous introduction of new technologies, new products, and new management measures, the problem of antimicrobial resistance must be controlled and alleviated.

Abstract:Antibiotic resistance affects the development of the world economy and threats public health. China is one of the countries with the most severe abuse of antibiotics. Here, we describe the causes of antibiotic resistance in the environment, human and animals as well as the status of antibiotic resistance. Based on the concept of One Health, we propose the promotion of the scientific use of antibiotics, the development of new types of antibiotics, establishment of the antibiotics stereoscopic monitoring network system, the promotion of knowledge education of antibiotic resistance, prevention of infection and other measures. We call for the establishment of interdisciplinary, cross-sectoral, trans-regional communication and cooperation to promote the development of antibiotic resistance prevention and control in China to protect environment and the health of humans and animals.