Analysis of multidrug-resistant determinants of clinically isolated Acinetobacter baumannii CYZ via whole genome sequencing.

Acinetobacter baumannii is a multidrug-resistant coccobacillus responsible for severe nosocomial infectious diseases. This study mainly focuses on investigating the antimicrobial resistance features of a clinically isolated strain (A. baumannii CYZ) using the PacBio Sequel II sequencing platform. The chromosomal size of A. baumannii CYZ is 3,960,760 bp, which contains a total of 3803 genes with a G + C content of 39.06%. Functional analysis performed using the Clusters of Orthologous Groups of Proteins (COGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, as well as the Comprehensive Antibiotic Resistance Database (CARD) revealed a complicated set of antimicrobial resistance determinants in the genome of A. baumannii CYZ, which were mainly classified into multidrug efflux pumps and transport systems, ß-lactamase relative and penicillin-binding proteins, aminoglycoside modification enzymes, alternation of antibiotic target sites, lipopolysaccharide relative, and other mechanisms. A total of 35 antibiotics were tested for the antimicrobial susceptibility of A. baumannii CYZ, and the organism exhibited a stronger antimicrobial resistance ability. The phylogenetic relationship indicated that A. baumannii CYZ has high homology with A. baumannii ATCC 17978; however, the former also exhibited its specific genome characteristics. Our research results give insight into the genetic antimicrobial-resistant features of A. baumannii CYZ as well as provide a genetic basis for the further study of the phenotype.

Ferrets: A powerful model of SARS-CoV-2.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recent years not only caused a global pandemic but resulted in enormous social, economic, and health burdens worldwide. Despite considerable efforts to combat coronavirus disease 2019 (COVID-19), various SARS-CoV-2 variants have emerged, and their underlying mechanisms of pathogenicity remain largely unknown. Furthermore, effective therapeutic drugs are still under development. Thus, an ideal animal model is crucial for studying the pathogenesis of COVID-19 and for the preclinical evaluation of vaccines and antivirals against SARS-CoV-2 and variant infections. Currently, several animal models, including mice, hamsters, ferrets, and non-human primates (NHPs), have been established to study COVID-19. Among them, ferrets are naturally susceptible to SARS-CoV-2 infection and are considered suitable for COVID-19 study. Here, we summarize recent developments and application of SARS-CoV-2 ferret models in studies on pathogenesis, therapeutic agents, and vaccines, and provide a perspective on the role of these models in preventing COVID-19 spread.

HBV precore G1896A mutation promotes growth of hepatocellular carcinoma cells by activating ERK/MAPK pathway.

Chronic hepatitis B virus (HBV) infection is one of the leading causes of hepatocellular carcinoma (HCC). The HBV genome is prone to mutate and several variants are closely related to the malignant transformation of liver disease. G1896A mutation (G to A mutation at nucleotide 1896) is one of the most frequently observed mutations in the precore region of HBV, which prevents HBeAg expression and is strongly associated with HCC. However, the mechanisms by which this mutation causes HCC are unclear. Here, we explored the function and molecular mechanisms of the G1896A mutation during HBV-associated HCC. G1896A mutation remarkably enhanced the HBV replication in vitro. Moreover, it increased tumor formation and inhibited apoptosis of hepatoma cells, and decreased the sensitivity of HCC to sorafenib. Mechanistically, the G1896A mutation could activate ERK/MAPK pathway to enhanced sorafenib resistance in HCC cells and augmented cell survival and growth. Collectively, our study demonstrates for the first time that the G1896A mutation has a dual regulatory role in exacerbating HCC severity and sheds some light on the treatment of G1896A mutation-associated HCC patients.

Regulation of Antiviral Immune Response by N 6-Methyladenosine of mRNA.

Host innate and adaptive immune responses play a vital role in clearing infected viruses. Meanwhile, viruses also evolve a series of mechanisms to weaken the host immune responses and evade immune defense. Recently, N 6-methyladenosine (m6A), the most prevalent mRNA modification, has been revealed to regulate multiple steps of RNA metabolism, such as mRNA splicing, localization, stabilization, and translation, thus participating in many biological phenomena, including viral infection. In the process of virus-host interaction, the m6A modification that presents on the virus RNA impedes capture by the pattern recognition receptors, and the m6A modification appearing on the host immune-related molecules regulate interferon response, immune cell differentiation, inflammatory cytokine production, and other immune responses induced by viral infection. This review summarizes the research advances about the regulatory role of m6A modification in the innate and adaptive immune responses during viral infections.

Hold Breath: Autonomic Neural Regulation of Innate Immunity to Defend Against SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel member of the genus of betacoronavirus, which caused a pandemic of coronavirus disease 2019 (COVID-19) worldwide. The innate immune system plays a critical role in eliminating the virus, which induces inflammatory cytokine and chemokine secretion, produces different interferons, and activates the adaptive immune system. Interactions between the autonomic nervous system and innate immunity release neurotransmitters or neuropeptides to balance the excess secretion of inflammatory cytokines, control the inflammation, and restore the host homeostasis. However, more neuro-immune mechanisms to defend against viral infection should be elucidated. Here, we mainly review and provide our understanding and viewpoint on the interaction between respiratory viral proteins and host cell receptors, innate immune responses to respiratory viral infection, and the autonomic neural regulation of the innate immune system to control respiratory viruses caused by lungs and airways inflammation.

Characteristic antimicrobial resistance of clinically isolated Stenotrophomonas maltophilia CYZ via complete genome sequence.

OBJECTIVES: Stenotrophomonas maltophilia is an important multidrug-resistant pathogen that is associated with various serious nosocomial infections. In our study, we investigated the antimicrobial resistance traits of clinical S. maltophilia strain CYZ isolated from the sputum of an immunocompromised patient. METHODS: The whole genome sequence of S. maltophilia CYZ was investigated using a PacBio RS II system. The functions of all the predicted genes were annotated by the COG, GO and KEGG databases. Several types of antibiotics were selected to test the antimicrobial susceptibility, and a phylogenetic tree was constructed based on 16S rRNA gene sequence. RESULTS: The genome of S. maltophilia CYZ has a length of 4,517,685 bp and contains 4077 predicted genes, with an average G + C content of 66.65%. Functional genomic analysis via the annotations of the COG and GO databases revealed that the isolate exhibited specific means to resist antibiotics. The annotated genes involved in flagella, pili or fimbriae, biofilm formation, polysaccharide and cyclic di-GMP may contribute to promote the ability of antimicrobial resistance. This strain showed susceptibility to levofloxacin, trimethoprim/sulfamethoxazole and minocycline according to antimicrobial susceptibility testing. The phylogenetic relationship indicated that S. maltophilia CYZ was closely related to S. maltophilia strains isolated from the nosocomial environment. CONCLUSIONS: The current results give a better understanding of the genetic characteristics of antimicrobial resistance in S. maltophilia CYZ and provide a genetic basis for further study of the phenotype.