
結核菌の細胞壁リモデリングに関与するタンパク質VirRは、細胞壁の透過性を維持することで小胞産生を制御している。


coremsg

Pathogenic and nonpathogenic mycobacteria secrete extracellular vesicles (EVs) under various conditions. EVs produced by Mycobacterium tuberculosis ( Mtb ) have raised significant interest for their potential in cell communication, nutrient acquisition, and immune evasion. However, the relevance of vesicle secretion during tuberculosis infection remains unknown due to the limited understanding of mycobacterial vesicle biogenesis. We have previously shown that a transposon mutant in the LCP-related gene virR ( virRmut ) manifested a strong attenuated phenotype during experimental macrophage and murine infections, concomitant to enhanced vesicle release. In this study, we aimed to understand the role of VirR in the vesicle production process in Mtb . We employ genetic, transcriptional, proteomics, ultrastructural and biochemical methods to investigate the underlying processes explaining the enhanced vesiculogenesis phenomenon observed in the virRmut . Our results establish that VirR is critical to sustain proper cell permeability via regulation of cell envelope remodeling possibly through the interaction with similar cell envelope proteins, which control the link between peptidoglycan and arabinogalactan. These findings advance our understanding of mycobacterial extracellular vesicle biogenesis and suggest that these set of proteins could be attractive targets for therapeutic intervention.

### Competing Interest Statement

The authors have declared no competing interest.

Maintenance of cell wall remodeling and vesicle production are connected in Mycobacterium tuberculosis

結核菌における細胞壁リモデリングの維持と小胞産生の関連性

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アルバータ州では、牛と人間の間の持続的な異種間伝播システムが大腸菌O157:H7感染の主要な原因となっている。特に、より毒性の高いstx2a遺伝子を持つ株が増加傾向にある。


Background Several areas of the world suffer notably high incidence of Shiga toxin-producing Escherichia coli , among them Alberta, Canada. We assessed the role of persistent cross-species transmission systems in Alberta’s E. coli O157:H7 epidemiology.

Methods We sequenced and assembled 229 E. coli O157:H7 isolates originating from collocated cattle (n=108) and human (n=121) populations from 2007-2015 in Alberta. We constructed a timed phylogeny using BEAST2 using a structured coalescent model. We then extended the tree with human isolates through 2019 (n=432) to assess the long-term disease impact of local persistent lineages. Shiga toxin gene ( stx ) profile was determined for all isolates.

Results During 2007 to 2015, we estimated 107 (95% HPD 101, 111) human lineages arose from cattle lineages, and 31 (95% HPD 22, 43) from other human lineages; i.e., 77.5% of human lineages arose from cattle lineages. We identified 11 persistent lineages local to Alberta, which were associated with 36.4% (95% CI 27.8%, 45.6%) of human isolates. Of 115 isolates in local persistent lineages, 6.1% carried only stx2a and the rest stx1a/stx2a . During the later period, six local persistent lineages continued to be associated with human illness, including 74.7% (95% CI 68.3%, 80.3%) of reported cases in 2018 and 2019. The stx profile of isolates in local persistent lineages shifted from the earlier period, with 51.2% encoding only stx2a .

Conclusions Our study identified multiple locally evolving lineages transmitted between cattle and humans persistently associated with E. coli O157:H7 illnesses for up to 13 years. Of concern, there was a dramatic shift in the local persistent lineages toward strains with the more virulent stx2a -only profile. We hypothesize that the large proportion of disease associated with local transmission systems is a principal cause of Alberta’s high E. coli O157:H7 incidence.

### Competing Interest Statement

The authors have declared no competing interest.

Persistent cross-species transmission systems dominate Shiga toxin-producing Escherichia coli O157:H7 epidemiology in a high incidence region: a genomic epidemiology study

アルバータ州における優勢な異種間伝播システムが大腸菌o157-h7の疫学を支配している-ゲノム疫学研究


アルバータ州における優勢な異種間伝播システムが大腸菌O157:H7の疫学を支配している: ゲノム疫学研究



SntBはアスペルギルス・フラバスの発育、二次代謝産物合成、および病原性を制御するために重要な役割を果たす。SntBは酸化ストレス応答経路を調節することで、これらの生物学的プロセスを調整する。


The epigenetic reader SntB was identified as an important transcriptional regulator of growth, development, and secondary metabolite synthesis in Aspergillus flavus . However, the underlying molecular mechanism is still unclear. In this study, sntB gene deletion (Δ sntB ), complementary (Com- sntB ), and HA tag fused to sntB ( sntB -HA) strains were constructed by using the homologous recombination method, respectively. Our results revealed that deletion of sntB inhibited the processes of mycelia growth, conidial production, sclerotia formation, aflatoxin synthesis, and ability to colonize host compared to wild type (WT), and the defective phenotype of knockout strain Δ sntB could be restored in its complementary strain Com- sntB . Chromatin immunoprecipitation sequencing (ChIP-seq) of sntB- HA and WT and RNA sequencing (RNA-seq) of Δ sntB and WT strains revealed that SntB played key roles in oxidative stress response of A. flavus . The function of catC (encode a catalase) gene was further analyzed based on the integration results of ChIP-seq and RNA-seq. In Δ sntB strain, the relative expression level of catC was significantly higher than in WT strain, while a secretory lipase encoding gene (G4B84_008359) was down-regulated. Under the stress of oxidant menadione sodium bisulfite (MSB), the deletion of sntB obvious down-regulated the expression level of catC . After deletion of catC gene, the mycelia growth, conidial production, and sclerotia formation were inhibited, while ROS level and aflatoxin production were increased compared to the WT strain. Results also showed that the inhibition rate of MSB to Δ catC strain was significantly lower than that of WT group and AFB1 yield of the Δ catC strain was significantly decreased than that of WT strain under the stress of MSB. Our study revealed the potential machinery that SntB regulated fungal morphogenesis, mycotoxin anabolism, and fungal virulence through the axle of from SntB to fungal virulence and mycotoxin bio-synthesis, i.e. H3K36me3 modification-SntB-Peroxisomes-Lipid hydrolysis-fungal virulence and mycotoxin bio-synthesis. The results of the study shed light into the SntB mediated transcript regulation pathway of fungal mycotoxin anabolism and virulence, which provided potential strategy for control the contamination of A. flavus and its aflatoxins.

### Competing Interest Statement

The authors have declared no competing interest.

SntB triggers the antioxidant pathways to regulate development and aflatoxin biosynthesis in Aspergillus flavus

アスペルギルス-フラバスにおいて-sntbはアフラトキシン生合成と発育を制御するために抗酸化経路を活性化する


アスペルギルス・フラバスにおいて、SntBはアフラトキシン生合成と発育を制御するために抗酸化経路を活性化する



腸球菌ファエシウムの分泌抗原A (SagA) ペプチドグリカン加水分解酵素は、細胞分離と宿主免疫の活性化に不可欠である。


Enterococcus faecium is a microbiota species in humans that can modulate host immunity[1][1], but has also acquired antibiotic resistance and is a major cause of hospital-associated infections[2][2]. Notably, diverse strains of E. faecium produce SagA, a highly conserved peptidoglycan hydrolase that is sufficient to promote intestinal immunity[3][3]–[5][4] and immune checkpoint inhibitor antitumor activity[6][5]. However, the functions of SagA in E. faecium were unknown. Here we report that deletion of sagA impaired E. faecium growth and resulted in bulged and clustered enterococci due to defective peptidoglycan cleavage and cell separation. Moreover, Δ sagA showed increased antibiotic sensitivity, yielded lower levels of active muropeptides, displayed reduced activation of the peptidoglycan pattern-recognition receptor NOD2, and failed to promote cancer immunotherapy. Importantly, plasmid-based expression of SagA, but not its catalytically-inactive mutant, restored Δ sagA growth, production of active muropeptides and NOD2 activation. SagA is therefore essential for E. faecium growth, stress resistance and activation of host immunity.

### Competing Interest Statement

The authors have declared no competing interest.

 [1]: #ref-1
 [2]: #ref-2
 [3]: #ref-3
 [4]: #ref-5
 [5]: #ref-6

Secreted antigen A peptidoglycan hydrolase is essential for Enterococcus faecium cell separation and priming of immune checkpoint inhibitor therapy

腸球菌ファエシウムの細胞分離と免疫チェックポイント阻害剤がん療法の活性化に不可欠な分泌抗原a-ペプチドグリカン加水分解酵素


腸球菌ファエシウムの細胞分離と免疫チェックポイント阻害剤がん療法の活性化に不可欠な分泌抗原A ペプチドグリカン加水分解酵素



バクテリアのバイオフィルム内での電気化学的コミュニケーションは、情報伝達と生存戦略に重要な役割を果たす。


バクテリアのバイオフィルムにおける電気化学的コミュニケーションの研究