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A bacteriophage nucleus-like compartment shields DNA from CRISPR nucleases 期刊论文
NATURE, 2020, 577 (7789) : 244-+
作者:  Mendoza, Senen D.;  Nieweglowska, Eliza S.;  Govindarajan, Sutharsan;  Leon, Lina M.;  Berry, Joel D.;  Tiwari, Anika;  Chaikeeratisak, Vorrapon;  Pogliano, Joe;  Agard, David A.;  Bondy-Denomy, Joseph
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

All viruses require strategies to inhibit or evade the immune pathways of cells that they infect. The viruses that infect bacteria, bacteriophages (phages), must avoid immune pathways that target nucleic acids, such as CRISPR-Cas and restriction-modification systems, to replicate efficiently(1). Here we show that jumbo phage phi KZ segregates its DNA from immunity nucleases of its host, Pseudomonas aeruginosa, by constructing a proteinaceous nucleus-like compartment. phi KZ is resistant to many immunity mechanisms that target DNA in vivo, including two subtypes of CRISPR-Cas3, Cas9, Cas12a and the restriction enzymes HsdRMS and EcoRI. Cas proteins and restriction enzymes are unable to access the phage DNA throughout the infection, but engineering the relocalization of EcoRI inside the compartment enables targeting of the phage and protection of host cells. Moreover, phi KZ is sensitive to Cas13a-a CRISPR-Cas enzyme that targets RNA-probably owing to phage mRNA localizing to the cytoplasm. Collectively, we propose that Pseudomonas jumbo phages evade a broad spectrum of DNA-targeting nucleases through the assembly of a protein barrier around their genome.


  
The stepwise assembly of the neonatal virome is modulated by breastfeeding 期刊论文
NATURE, 2020
作者:  Medina, Christopher B.;  Mehrotra, Parul;  Arandjelovic, Sanja;  Perrys, Justin S. A.;  Guo, Yizhan;  Morioka, Sho;  Barron, Brady;  Walk, Scott F.;  Ghesquiere, Bart;  Lorenz, Ulrike;  Krupnick, Alexander S.;  Ravichandran, Kodi S.
收藏  |  浏览/下载:36/0  |  提交时间:2020/07/03

The infant gut is colonized first by temperate bacteriophages induced from pioneer bacteria and later by viruses that replicate in human cells, the populations of which are modulated by breastfeeding.


The gut of healthy human neonates is usually devoid of viruses at birth, but quickly becomes colonized, which-in some cases-leads to gastrointestinal disorders(1-4). Here we show that the assembly of the viral community in neonates takes place in distinct steps. Fluorescent staining of virus-like particles purified from infant meconium or early stool samples shows few or no particles, but by one month of life particle numbers increase to 10(9) per gram, and these numbers seem to persist throughout life(5-7). We investigated the origin of these viral populations using shotgun metagenomic sequencing of virus-enriched preparations and whole microbial communities, followed by targeted microbiological analyses. Results indicate that, early after birth, pioneer bacteria colonize the infant gut and by one month prophages induced from these bacteria provide the predominant population of virus-like particles. By four months of life, identifiable viruses that replicate in human cells become more prominent. Multiple human viruses were more abundant in stool samples from babies who were exclusively fed on formula milk compared with those fed partially or fully on breast milk, paralleling reports that breast milk can be protective against viral infections(8-10). Bacteriophage populations also differed depending on whether or not the infant was breastfed. We show that the colonization of the infant gut is stepwise, first mainly by temperate bacteriophages induced from pioneer bacteria, and later by viruses that replicate in human cells  this second phase is modulated by breastfeeding.


  
Action of a minimal contractile bactericidal nanomachine 期刊论文
NATURE, 2020, 580 (7805) : 658-+
作者:  Peng, Ruchao;  Xu, Xin;  Jing, Jiamei;  Wang, Min;  Peng, Qi;  Liu, Sheng;  Wu, Ying;  Bao, Xichen;  Wang, Peiyi;  Qi, Jianxun;  Gao, George F.;  Shi, Yi
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/03

The authors report near-atomic resolution structures of the R-type bacteriocin from Pseudomonas aeruginosa in the pre-contraction and post-contraction states, and these structures provide insight into the mechanism of action of molecular syringes.


R-type bacteriocins are minimal contractile nanomachines that hold promise as precision antibiotics(1-4). Each bactericidal complex uses a collar to bridge a hollow tube with a contractile sheath loaded in a metastable state by a baseplate scaffold(1,2). Fine-tuning of such nucleic acid-free protein machines for precision medicine calls for an atomic description of the entire complex and contraction mechanism, which is not available from baseplate structures of the (DNA-containing) T4 bacteriophage(5). Here we report the atomic model of the complete R2 pyocin in its pre-contraction and post-contraction states, each containing 384 subunits of 11 unique atomic models of 10 gene products. Comparison of these structures suggests the following sequence of events during pyocin contraction: tail fibres trigger lateral dissociation of baseplate triplexes  the dissociation then initiates a cascade of events leading to sheath contraction  and this contraction converts chemical energy into mechanical force to drive the iron-tipped tube across the bacterial cell surface, killing the bacterium.


  
Targeting of temperate phages drives loss of type I CRISPR-Cas systems 期刊论文
NATURE, 2020, 578 (7793) : 149-+
作者:  Xiang, Lifeng;  Yin, Yu;  Zheng, Yun;  Ma, Yanping;  Li, Yonggang;  Zhao, Zhigang;  Guo, Junqiang;  Ai, Zongyong;  Niu, Yuyu;  Duan, Kui;  He, Jingjing;  Ren, Shuchao;  Wu, Dan;  Bai, Yun;  Shang, Zhouchun;  Dai, Xi;  Ji, Weizhi;  Li, Tianqing
收藏  |  浏览/下载:27/0  |  提交时间:2020/07/03

On infection of their host, temperate viruses that infect bacteria (bacteriophages  hereafter referred to as phages) enter either a lytic or a lysogenic cycle. The former results in lysis of bacterial cells and phage release (resulting in horizontal transmission), whereas lysogeny is characterized by the integration of the phage into the host genome, and dormancy (resulting in vertical transmission)(1). Previous co-culture experiments using bacteria and mutants of temperate phages that are locked in the lytic cycle have shown that CRISPR-Cas systems can efficiently eliminate the invading phages(2,3). Here we show that, when challenged with wild-type temperate phages (which can become lysogenic), type I CRISPR-Cas immune systems cannot eliminate the phages from the bacterial population. Furthermore, our data suggest that, in this context, CRISPR-Cas immune systems are maladaptive to the host, owing to the severe immunopathological effects that are brought about by imperfect matching of spacers to the integrated phage sequences (prophages). These fitness costs drive the loss of CRISPR-Cas from bacterial populations, unless the phage carries anti-CRISPR (acr) genes that suppress the immune system of the host. Using bioinformatics, we show that this imperfect targeting is likely to occur frequently in nature. These findings help to explain the patchy distribution of CRISPR-Cas immune systems within and between bacterial species, and highlight the strong selective benefits of phage-encoded acr genes for both the phage and the host under these circumstances.


CRISPR-Cas systems cannot eliminate temperate bacteriophages from bacterial populations and-in this context-the systems impose immunopathological costs on the host, creating selective pressures that may explain their patchy distribution in bacteria.


  
VIROLOGY Phages make a group decision 期刊论文
NATURE, 2017, 541 (7638) : 466-467
作者:  Davidson, Alan R.
收藏  |  浏览/下载:0/0  |  提交时间:2019/04/09
In situ structures of the genome and genome-delivery apparatus in a single-stranded RNA virus 期刊论文
NATURE, 2017, 541 (7635) : 112-+
作者:  Dai, Xinghong;  Li, Zhihai;  Lai, Mason;  Shu, Sara;  Du, Yushen;  Zhou, Z. Hong;  Sun, Ren
收藏  |  浏览/下载:9/0  |  提交时间:2019/04/09