Mycobacterium tuberculosis PE_PGRS18 enhances the intracellular survival of M. smegmatis via altering host macrophage cytokine profiling and attenuating the cell apoptosis.

Mycobacterium tuberculosis PE/PPE family proteins, named after the presence of conserved PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains at N-terminal, are prevalent in M. tuberculosis genome. The function of most PE/PPE family proteins remains elusive. To characterize the function of PE_PGRS18, the encoding gene was heterologously expressed in M. smegmatis, a nonpathogenic mycobacterium. The recombinant PE_PGRS18 is cell wall associated. M. smegmatis PE_PGRS18 recombinant showed differential response to stresses and altered the production of host cytokines IL-6, IL-1ß, IL-12p40 and IL-10, as well as enhanced survival within macrophages largely via attenuating the apoptosis of macrophages. In summary, the study firstly unveiled the role of PE_PGRS18 in physiology and pathogenesis of mycobacterium.

Erratum to: The discovery of potent immunostimulatory CpG-ODNs widely distributed in bacterial genomes.

In the article by Liu et al. published in Journal of Microbiology 2020; 58, 153-162, 1# The Supplementary data's consecutive numbers (Supplementary data Fig. S2) on 9th line of 4th paragraph in the section of 'Discussion.' on page 160 should be corrected in (Supplementary data Fig. S1). The sentence should have read: The results showed that the nonspecific internalization of T03 had only a slight competition with CpG-ODNs (Supplementary data Fig. S1).2# The Supplementary data's consecutive numbers (Supplementary data Fig. S3) on 13th line of 6th paragraph in the section of 'Discussion.' on page 161 should be corrected in (Supplementary data Fig. S2). The sentence should have read: Although the CpG-ODNs screened in this study had no or weak stimulation effect on human PBMCs (Supplementary data Fig. S2), it once again indicated that CpG-ODNs can be species-specific.And the Electronic Supplementary Material should be corrected as below. We apologize for any inconvenience that this may have caused.

The discovery of potent immunostimulatory CpG-ODNs widely distributed in bacterial genomes.

Oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG-ODN) can be specifically recognized by Toll-like receptor 9 (TLR9), provoking innate immune responses. Designed according to this structural feature, many synthetic phosphorothioate CpG-ODNs successfully activate macrophages. However, it is difficult to find potent stimulatory CpG-DNA fragments in microbial genomes. Therefore, whether microbial CpG-DNA substantially contributes to infectious and immune diseases remains controversial. In this study, high-throughput scanning was carried out for thousands of bacterial genomes with bioinformatics tools to comprehensively evaluate the distribution of CpG-DNA fragments. A random sampling test was then performed to verify their immunostimulatory properties by experiments in vitro and in vivo. Natural TLR9-dependent and potent stimulatory CpG-DNA fragments were found in microbial genomes. Interestingly, highly conserved stimulatory CpG-DNA fragments were found in 16S and 23S rDNA sequences with multiple copies, while others were species-specific. Additionally, we found that the reported active motifs were mostly non-stimulatory in natural CpG fragments. This evidence indicates that the previous structural descriptions of functional CpG-ODNs are incomplete. Our study has assessed the distribution of microbial CpG-DNA fragments, and identified natural stimulatory CpG-DNA fragments. These findings provide a deeper understanding of CpG-ODN structures and new evidence for microbial DNA inflammatory function and pathogenicity.