ArsR Family Regulator MSMEG_6762 Mediates the Programmed Cell Death by Regulating the Expression of HNH Nuclease in Mycobacteria

Programmed cell death (PCD) is the result of an intracellular program and is accomplished by a regulated process in both prokaryotic and eukaryotic organisms. Here, we report a programed cell death process in Mycobacterium smegmatis, an Actinobacteria species which involves a transcription factor and a DNase of the HNH family. We found that over-expression of an ArsR family member of the transcription factor, MSMEG_6762, leads to cell death. Transcriptome analysis revealed an increase in the genes’ transcripts involved in DNA repair and homologous recombination, and in three members of HNH family DNases. Knockout of one of the DNase genes, MSMEG_1275, alleviated cell death and its over-expression of programmed cell death. Purified MSMEG_1275 cleaved the M. smegmatis DNA at multiple sites. Overall, our results indicate that the MSMEG_6762 affects cell death and is mediated, at least partially, by activation of the HNH nuclease expression under a stress condition

The Global Reciprocal Reprogramming between Mycobacteriophage SWU1 and Mycobacterium Reveals the Molecular Strategy of Subversion and Promotion of Phage Infection

Bacteriophages are the viruses of bacteria, which have contributed extensively to our understanding of life and modern biology. The phage-mediated bacterial growth inhibition represents immense untapped source for novel antimicrobials. Insights into the interaction between mycobacteriophage and Mycobacterium host will inform better utilizing of mycobacteriophage. In this study, RNA sequencing technology (RNA-seq) was used to explore the global response of Mycobacterium smegmatis mc2 155 at an early phase of infection with mycobacteriophage SWU1, key host metabolic processes of M. smegmatis mc2 155 shut off by SWU1, and the responsible phage proteins. The results of RNA-seq were confirmed by Real-time PCR and functional assay. 1174 genes of M. smegmatis mc2 155 (16.9% of the entire encoding capacity) were differentially regulated by phage infection. These genes belong to six functional categories: (i) signal transduction, (ii) cell energetics, (iii) cell wall biosynthesis, (iv) DNA, RNA, and protein biosynthesis, (v) iron uptake, (vi) central metabolism. The transcription patterns of phage SWU1 were also characterized. This study provided the first global glimpse of the reciprocal reprogramming between the mycobacteriophage and Mycobacterium host

Epidemiological and genomic analyses of human isolates of Streptococcus suis between 2005 and 2021 in Shenzhen, China

Streptococcus suis (S. suis) is an important food-borne zoonotic pathogen that causes swine streptococcosis, which threatens human health and brings economic loss to the swine industry. Three-quarters of human S. suis infections are caused by serotype 2. A retrospective analysis of human S. suis cases in Shenzhen, a megacity in China, with high pork consumption, between 2005 and 2021 was conducted to understand its genomic epidemiology, pathogen virulence, and drug resistance characteristics. The epidemiological investigation showed that human cases of S. suis in Shenzhen were mainly associated with people who had been in close contact with raw pork or other swine products. Whole-genome sequence analysis showed that 33 human isolates in Shenzhen were dominated by serotype 2 (75.76%), followed by serotype 14 (24.24%), and the most prevalent sequence types (STs) were ST7 (48.48%) and ST1 (39.40%). ST242 (9.09%) and ST25 (3.03%), which were rarely reported, were also found. Phylogenetic analysis showed that the Shenzhen human isolates had close genetic relatedness to isolates from Guangxi (China), Sichuan (China), and Vietnam. We found a new 82 KB pathogenicity island (PAI) in the serotype 2 isolate that may play a role in sepsis. Similarly, a serotype 14 isolate, containing 78 KB PAI, was isolated from a patient presenting with streptococcal toxic shock syndrome (STSLS) who subsequently died. Multi-drug resistance (MDR) was high in human isolates of S. suis from Shenzhen. Most human isolates were resistant to tetracycline, streptomycin, erythromycin, and clindamycin, and 13 isolates had intermediate resistance to penicillin. In conclusion, swine importation from Guangxi, Sichuan, and Vietnam should be more closely monitored, and the use of antibiotics limited to reduce the potential for antimicrobial resistance (AMR)

Molecular Toxicity of Metal Oxide Nanoparticles in <i>Danio rerio</i>

Metal oxide nanoparticles can exert adverse effects on humans and aquatic organisms; however, their toxic mechanisms are still unclear. We investigated the toxic effects and mechanisms of copper oxide, zinc oxide, and nickel oxide nanoparticles in <i>Danio rerio</i> using microarray analysis and the comet assay. Copper oxide nanoparticles were more lethal than the other metal oxide nanoparticles. Gene ontology analysis of genes that were differentially expressed following exposure to all three metal oxide nanoparticles showed that the nanoparticles mainly affected nucleic acid metabolism in the nucleus via alterations in nucleic acid binding. KEGG analysis classified the differentially expressed genes to the genotoxicity-related pathways “cell cycle”, “Fanconi anemia”, “DNA replication”, and “homologous recombination”. The toxicity of metal oxide nanoparticles may be related to impairments in DNA synthesis and repair, as well as to increased production of reactive oxygen species

Molecular Toxicity of Metal Oxide Nanoparticles in <i>Danio rerio</i>

Metal oxide nanoparticles can exert adverse effects on humans and aquatic organisms; however, their toxic mechanisms are still unclear. We investigated the toxic effects and mechanisms of copper oxide, zinc oxide, and nickel oxide nanoparticles in <i>Danio rerio</i> using microarray analysis and the comet assay. Copper oxide nanoparticles were more lethal than the other metal oxide nanoparticles. Gene ontology analysis of genes that were differentially expressed following exposure to all three metal oxide nanoparticles showed that the nanoparticles mainly affected nucleic acid metabolism in the nucleus via alterations in nucleic acid binding. KEGG analysis classified the differentially expressed genes to the genotoxicity-related pathways “cell cycle”, “Fanconi anemia”, “DNA replication”, and “homologous recombination”. The toxicity of metal oxide nanoparticles may be related to impairments in DNA synthesis and repair, as well as to increased production of reactive oxygen species

Molecular Toxicity of Metal Oxide Nanoparticles in <i>Danio rerio</i>

Metal oxide nanoparticles can exert adverse effects on humans and aquatic organisms; however, their toxic mechanisms are still unclear. We investigated the toxic effects and mechanisms of copper oxide, zinc oxide, and nickel oxide nanoparticles in <i>Danio rerio</i> using microarray analysis and the comet assay. Copper oxide nanoparticles were more lethal than the other metal oxide nanoparticles. Gene ontology analysis of genes that were differentially expressed following exposure to all three metal oxide nanoparticles showed that the nanoparticles mainly affected nucleic acid metabolism in the nucleus via alterations in nucleic acid binding. KEGG analysis classified the differentially expressed genes to the genotoxicity-related pathways “cell cycle”, “Fanconi anemia”, “DNA replication”, and “homologous recombination”. The toxicity of metal oxide nanoparticles may be related to impairments in DNA synthesis and repair, as well as to increased production of reactive oxygen species

Molecular Toxicity of Metal Oxide Nanoparticles in <i>Danio rerio</i>

Metal oxide nanoparticles can exert adverse effects on humans and aquatic organisms; however, their toxic mechanisms are still unclear. We investigated the toxic effects and mechanisms of copper oxide, zinc oxide, and nickel oxide nanoparticles in <i>Danio rerio</i> using microarray analysis and the comet assay. Copper oxide nanoparticles were more lethal than the other metal oxide nanoparticles. Gene ontology analysis of genes that were differentially expressed following exposure to all three metal oxide nanoparticles showed that the nanoparticles mainly affected nucleic acid metabolism in the nucleus via alterations in nucleic acid binding. KEGG analysis classified the differentially expressed genes to the genotoxicity-related pathways “cell cycle”, “Fanconi anemia”, “DNA replication”, and “homologous recombination”. The toxicity of metal oxide nanoparticles may be related to impairments in DNA synthesis and repair, as well as to increased production of reactive oxygen species

The Synergistic Effect of Exogenous Glutamine and Rifampicin Against Mycobacterium Persisters

Persisters, stochastic dormant variants of normal bacteria cell, represent a significant portion of the survivors upon exposure to antibiotics and other environmental stresses, which contributes substantially to high level antibiotics tolerance. Glutamine is a crucial component of the Mycobacteria nitrogen pool that is indispensable for survival upon stresses. To study whether a synergistic effect exists between glutamine and antibiotics against Mycobacterial persisters, the efficacy of rifampicin alone or together with exogenous glutamine upon Mycobacterium smegmatis mc2 155 persisters was monitored. The result showed that glutamine decreases M. smegmatis tolerance to rifampicin upon starvation. The reactive oxygen species level of the strains treated with rifampicin and glutamine increased. The synergism of glutamine and rifampicin to kill persisters might derive from altering the oxidative phosphorylation and TCA cycle, as both evidenced by both ATP level increase and transcriptome change. Glutamine might represent a synergistic agent of rifampicin to kill Mycobacteria persisters