Practical Nanozymes Discovered to Fight Antimicrobial Resistance (Biology)

Nanozymes, a group of inorganic catalysis-efficient particles, have been proposed as promising antimicrobials against bacteria. They are efficient in killing bacteria, thanks to their production of reactive oxygen species (ROS).

Despite this advantage, nanozymes are generally toxic to both bacteria and mammalian cells, that is, they are also toxic to our own cells. This is mainly because of the intrinsic inability of ROS to distinguish bacteria from mammalian cells.

In a study published in Nature Communications, the research team led by XIONG Yujie and YANG Lihua from University of Science and Technology (USTC) of the Chinese Academy of Sciences (CAS) proposed a novel method to construct efficient-while-little-toxic nanozymes.

The researchers showed that nanozymes that generate surface-bound ROS selectively kill bacteria, while leaving the mammalian cells safe.

The selectivity is attributed to, on the one hand, the surface-bound nature of ROS generated by the nanozymes prepared by the team, and on the other hand, an unexpected antidote role of endocytosis, a cellular process that is common for mammalian cells while absent in bacteria.

Moreover, the researchers observed a few different nanozymes that generate surface-bound ROS but vary in chemical components and in physical structures, ending up finding that the anti-bacteria behaviors are similar. This fact brings to the conclusion that the advantage of selectively killing bacteria over mammalian cells is the general property of the nanozymes that produce surface-bound ROS.

Antimicrobial resistance (AMR) poses a threat to global health, which is the reason why our use of drugs against germs are gradually less effective.

Featured image: Transmission electron microscopy (TEM) images of AgPd nanocages with different Pd content. © Feng Gao et al.


Reference

Surface-bound reactive oxygen species generating nanozymes for selective antibacterial action


Provided by Chinese Academy of Sciences

Scientists Reveal New Mechanism of Xenogeneic Silencing in Bacteria (Biology)

Lateral gene transfer (LGT) plays a prominent role in the genome evolution and environmental adaptation of prokaryotes.

Xenogeneic silencing proteins can selectively silence the newly acquired DNA molecules to protect cells from the detrimental effects of LGT genes. H-NS, a nucleoid-associated DNA-binding protein, is an important xenogeneic silencer.  

Recently, Dr. LIU Xiaoxiao and other researchers in Dr. WANG Xiaoxue’s group from the South China Sea Institute of Oceanology (SCSIO) of the Chinese Academy of Sciences found a key process of xenogeneic silencing by studying Shewanella. The silencing of prophage relied on a temperature-dependent posttranslational modification of the host H-NS in S. oneidensis.

This work was published in Nucleic Acids Research on March 8. It is the first to show that posttranslational modification of H-NS can function as a regulatory switch to regulate the prophage activity in host genomes.  

Researchers from WANG’s group showed that H-NS “silenced” the prophage by recognizing the excisionase of the prophage. At room temperature, most of the H-NS protein in the cell was phosphorylated. Phosphorylated H-NS could silence the expression of cytotoxic genes on the prophage.

However, low temperature promoted the dephosphorylation of H-NS and changed the binding of H-NS to DNA, which relieved these genes expression. By this way, the H-NS silenced the specific prophage and helped Shewanella to adapt to the low temperature environment.  

Specifically, phosphorylation of H-NS at Ser42 was critical for silencing the cold-inducible genes including the excisionase of CP4So prophage, a cold shock protein, and a stress-related chemosensory system. By contrast, nonphosphorylated H-NS derepressed the promoter activity of these genes/operons to enable their expression at cold temperatures. 

The results of the study illustrate a new way of decision-making for xenogeneic silencing in response to temperature shifts in bacteria and provide new insights for our understanding of how bacteria silence and activate the LGT genes in response to environmental changes.  

Featured image: A proposed mechanism of xenogeneic silencing by H-NS (Image by LIU Xiaoxiao, SCSIO)


Reference

Xenogeneic silencing relies on temperature-dependent phosphorylation of the host H-NS protein in Shewanella


Provided by Chinese Academy of Sciences

Researchers Reveal Host Preference and Specialization toward Fungal Assemblages in Mycoheterotrophs (Botany)

Mycoheterotrophs are a group of plants having lost chlorophylls, parasitic on mycorrhizal fungi. They are the “aliens” of the plant world because of their rarity and weird looks. Non-green full mycoheterotrophs live their life completely depending on fungi, usually maintain more specialized fungal relationships than autotrophs: it is thought that the plant-fungi interactions may have driven their evolution. However, it remains poorly known about the relationships between mycoheterotrophs and fungal partners: for example, do mycoheterotrophs select their fungal partners inheritably stable or recruit their partners locally?

The genus Burmannia (Burmanniaceae) is one of the few genera of land plants that contain both fully mycoheterotrophic species and green autotrophic species. Therefore, it provides an excellent chance to study the change in fungal partners that accompanies the evolution of mycoheterotrophy.

Recently, ZHAO Zhongtao and his collaborators from the South China Botanical Garden of the Chinese Academy of Sciences collected a large number of different species from South China and southeast Asia, including autotrophs, partial mycoheterotrophs, and full mycoheterotrophs, and investigated the fungal communities in the plant roots using DNA sequencing methods.

According to their results, although many fungal species were shared by different Burmannia species, fully mycoheterotrophic species typically host species-specific fungal assemblages, suggesting that they have a preference for the selected fungi. 

“The specialization toward fungal assemblages in mycoheterotrophs may be helpful in improving nutritional efficiency for plant parasites, and might be a balance of maximizing benefit from their fungal partners and increasing diversity of fungal partners to explore niche breadth,” said ZHAO, these fungi are a subset of the partners found in the autotrophic species, suggesting that the specialization results from a loss in fungal partners.

Interestingly, although mycoheterotrophs have such tight relationships with their fungal partners, the researchers found no apparent co-phylogenetic relationships between them. 

This study has been online published in The ISME Journal with the title of “Specificity of assemblage, not fungal partner species, explains mycorrhizal partnerships of mycoheterotrophic Burmannia plants.” 

Featured image: Autotrophs, partial mycoheterotrophs, and full mycoheterotrophs in Burmannia (Image by SCBG)


Reference

Specificity of assemblage, not fungal partner species, explains mycorrhizal partnerships of mycoheterotrophic Burmannia plants


Provided by Chinese Academy of Sciences

Scientists Reveal Structure of PSI-LHCI Supercomplex in Moss Physcomitrella patens (Botany)

Bryophytes (liverworts, mosses, and hornworts) are the first group of plants that shifted from aquatic to terrestrial environments, and thus are among the ancestor of the land plants. Therefore, the organization of photosystem I (PSI)-light harvesting complex I (LHCI) supercomplex of bryophytes is of great interest for understanding the transition of the photosynthetic apparatus from aquatic to terrestrial environments during the evolution of green plants.  

Researchers from the Institute of Botany of the Chinese Academy of Sciences (IBCAS) purified the PSI-LHCI supercomplex from the moss Physcomitrium patens (P. patens), a model plant of bryophytes, and solved its structure at an overall resolution of 3.23 Å using single-particle cryo-electron microscopy (cryo-EM).  

The structure showed that the PSI-LHCI of P. patens (Pp PSI-LHCI) is composed of four light harvesting antenna proteins (Lhca1, Lhca2, Lhca3 and Lhca5), which is the same as the number of LHCIs in the structure of higher plant PSI-LHCI, but Lhca5 in P. patens is replaced by Lhca4 in higher plants.

Fig. 2. Plausible energy transfer pathways from LHCI to the PSI core of P. patens. (Image by IBCAS)

At the junction of Lhca5/Lhca2 and PsaF, a special chlorophyll molecule (Chl 305) was found to be present only in the P. patens PSI-LHCI. This Chl contributes to the efficient energy transfer from Lhca5/Lhca2 to the PSI core.  

Compared with the green algae living in water, Pp PSI-LHCI has less light harvesting proteins and reduced light harvesting cross section, whereas it has more efficient energy transfer pathway than that of higher plant PSI-LHCI. This may be related to the low light environment that mosses experience after landing, as reducing light harvesting cross section helps to avoid light damage whereas fast light harvesting helps them to survive.  

These results shed light on the mechanisms of light-energy harvesting and transfer in the PSI-LHCI from bryophytes, and provide important clues to the changes that have occurred in PSI-LHCI from aquatic to land plants during evolution.  

This research has been published in Cell Discovery on February 16th, 2021 entitled “Antenna arrangement and energy transfer pathways of PSI-LHCI from the moss Physcomitrella patens“. 

Featured image: Overall structure of the PSI-LHCI supercomplex from P. patens. (Image by IBCAS)


Reference

Antenna arrangement and energy-transfer pathways of PSI–LHCI from the moss Physcomitrella patens


Provided by Chinese Academy of Sciences

Researchers Reveal Molecular Mechanism of Novel Heme-copper Terminal Oxidase Utilizing Two Electron Donors (Biology)

The heme-copper terminal oxidases (HCOs) superfamily, one of the most important metalloproteinases, is responsible for the efficient electron transfer from cytochrome c or quinol to molecular oxygen. The members of this family are multi-subunit complexes. In the complex, there is a conserved central catalytic subunit I, containing two heme groups and a copper atom (CuB), and the active site is formed by one high-spin heme and CuB. Subunit II usually contains binuclear CuA center.

Cytochrome c oxidase (CcO) family belongs to the HCOs superfamily, but could only use cytochrome c as electron donor according to previous studies. Recently, a novel CcO from the hyperthermophilic bacterium Aquifex aeolicus (AaCcO) was discovered to be able to use both cytochrome c and naphthoquinol (NQ) as electron donors, but its molecular mechanism as well as the evolutionary significance are still unknown.

In a study published online in Angewandte Chemie International Edition, the researchers from SUN Fei’s group at Institute of Biophysics of the Chinese Academy of Sciences, and Hartmut Michel’s group at Max Planck Institute of Biophysics, solved the 3.4 Å resolution electron cryo-microscopic structure of AaCcO.

AaCcO forms a novel dimeric structure mediated by subunit I (CoxA2), and different from that of all other reported CcO dimers.

The researchers observed fruitful protein-lipid interactions in the dimeric interface and found a novel substrate binding site of the NQ at the dimeric interface, which could allow NQ be a direct electron donor bypassing cytochrome c. As a result, it seems that AaCcO dimer should be the necessary condition for direct electron transfer from NQ.

Moreover, they found that the adapted structure of AaCcO has only one available proton pathway (K pathway) and a V-shaped unobstructed oxygen channel with more hydrophobic residues blocking one entry, which appeared to be evolutionary advantageous to keep the balance between its enzymatic activity and structural stability in the hyperthermophilic environment.

These results provide structural basis for molecular mechanism and the evolutionary significance of CcOs in the extreme thermal environment.


Reference

The unusual homodimer of a heme-copper terminal oxidase allows itself to utilize two electron donors


Provided by Chinese Academy of Sciences

Genome Scalpel Invented for Industrial Microalgae to Efficiently Turn CO2 into Biofuel (Botany)

A single-celled alga undergoes genome surgery to remove non-essential parts. This can lead to a most efficient cellular factory for producing sustainable biofuels from sunlight and carbon dioxide. 

Researchers from the Qingdao Institute of BioEnergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences (CAS) have stripped hundred-kilobase genome from a type of oil-producing microalgae, knocking out genes non-essential for it to function. By doing so, they have created a “genome scalpel” that can trim microalgal genomes rapidly and creatively.

The ‘minimal genome’ microalgae produced is potentially useful as a model organism for further study of the molecular and biological function of every gene, or as a ‘chassis’ strain for synthetic biologists to augment for customized production of biomolecules such as biofuels or bioplastics.

The study was published in The Plant Journal on March 14, 2021. 

Creation of a ‘minimal genome’ — a genome stripped of all duplicated or apparently non-functional ‘junk genes’ — can be very useful for investigating fundamental questions about genetic function and for designing cell factories that produce valuable compounds.

Such minimal genomes have been created for simple organisms, but rarely for eukaryotic organisms, including algae or plants. In higher eukaryotes, “junk” regions can take up to 70 percent of the genome. Deleting what only appears to be “junk genes” in fact can have harmful effects on the organism or even kill it. 

For the first time, researchers from QIBEBT have produced a genome with targeted deletions, of hundred kilobases in size each, for a type of algae called Nannochloropsis oceanica

N. oceanica are microalgae (single-celled algae) that have tremendous potential for production of biofuels, biomaterials and other platform chemicals in a renewable and sustainable manner while reducing greenhouse gas emissions. However, realizing the potential of these microalgae requires extensive genetic engineering of the organism to maximize yields and minimize production costs. 

The QIBEBT team first identified the non-essential chromosomal regions — ones whose genes were rarely expressed, or activated. They identified ten such ‘low-expression regions’, or LERs. They then used CRISPR-Cas9 gene-editing technique to snip out two of the largest LERs — over 200 kilobases in size. 

“Despite the all snipping, the microalgae still showed essentially normal growth, lipid content, fatty acid saturation levels and photosynthesis,” said study first-author WANG Qintao, of the Single-Cell Center (SCC) in the QIBEBT. “In some cases, there was even a slightly higher growth rate and biomass productivity than the organism in the wild.” 

“We interestingly found normal telomeres in the telomere-deletion mutants of Chromosome 30,” said the corresponding author XU Jian, of the SCC in QIBEBT. “This phenomenon implies the losing of distal part of chromosome may induce telomere regeneration.” 

Already, the substantially snipped genome should serve as a closer-to-minimal genome in Nannochloropsis, which can serve as the chassis strain for customized production of biomolecules using further metabolic engineering atop this chassis.  

Now that they have proven they can strip down the genome of such a complex eukaryote, the researchers now want to see if they can snip out still further LERs and other non-lethal regions, to craft a fully minimal Nannochloropsis that makes biofuels from CO2 with the highest efficiency. 

Featured image: Hundred-kilobase fragment deletions in microalgae by Cas9 cleavages. This figure was made using BioRender. (Image by LIU Yang)


Reference

Genome engineering of Nannochloropsis with hundred‐kilobase fragment deletions by Cas9 cleavages


Provided by Chinese Academy of Sciences

Researchers Develop Acid-sensitive Nanoparticles as New Treatment for Pancreatic Cancer (Medicine)

The research team led by Prof. YANG Lihua from Hefei National Laboratory for Physical Sciences at the Microscale, School of Chemistry and Materials Science of the University of Science and Technology of China (USTC) of the Chinese Academy of Sciences proposed nanomicelles composed solely of macromolecules as a new approach for treating pancreatic tumor. The study was published in ACS Applied Materials & Interfaces.

Host dense peptides (HDP) is a part of the innate immunity of eukaryotic organism. It helps the host fence back attack by microbes through disrupting cellular membrane integrity. Inspired by HDP, membrane-disruptive macromolecules are designed with two most HDP’s common structural characteristics (cationic and amphipathic) to realize similar membrane-disrupting function so that drug-resistant cancer cells can be efficiently eliminate. The onset of drug resistance is delayed after repeat treatment, suggesting the potential for addressing the cancer resistance issue. 

Despite these advantages, membrane-disruptive macromolecules normally cannot distinguish cancerous from normal cells. How to make membrane-disruptive macromolecules preferentially active to cancerous cells over normal cells is a significant challenge. 

In this study, the researchers used an acid-sensitive, membrane-disruptive micelle (M-14K) as the model for such nanoparticles.

This long-circulating nanoparticle showed acid-activated cytotoxicity indiscriminately to both cancerous and fibroblast cells, which is realized by acid-activatable disruption of cellular membrane integrity. The ability of such nanoparticles to penetrate the stromal barrier and eliminate the sheltered cancer cells was verified both in vitro using three-dimensional (3D) cell spheroids and in vivo using mouse models bearing BxPC-3 tumors. 

Notably, through animal experiments, the researchers found that the expression of extracellular matrix components was significantly suppressed, the tumor tissue was transformed into a less dense structure, and stroma was remodeled, without promoting tumor metastasis. 

Using acid-responsive nanoparticles composed solely of membrane-disruptive macromolecules, stroma remodeling and cancerous cells elimination can be realized simultaneously. This approach may open a new avenue for the development of efficacious drugs inhibiting pancreatic tumor growth and metastasis. 

What makes pancreatic tumor hard to cure is the dense stromal barriers sheltering cancerous cells. The penetration of drugs is hindered. To promote the infiltration of therapeutics, an adjuvant is used prior to gemcitabine to remodel the stroma. Nevertheless, this widely studied strategy may raise the risk of tumor metastasis and tumor cells’ resistance to drugs.

Featured image: Graphical abstract by Feng Fan et al.


Reference

pH-Sensitive Nanoparticles Composed Solely of Membrane-Disruptive Macromolecules for Treating Pancreatic Cancer


Provided by Chinese Academy of Sciences

New Species of Mint Family Found in Northern Myanmar (Botany)

Premna is a genus of the mint family (Lamiaceae) of flowering plants. Over the past 20 years, two new species of the genus (P. bhamoensis and P. grandipaniculata) have been reported or described from Kachin State of northern Myanmar, one of the richest plant diversity centers in Southeast Asia. 

During a fieldwork in 2018, researchers from the Xishuangbanna Tropical Botanical Garden (XTBG) collected an unknown Premna woody climber from Putao District of Kachin State. After careful morphological studies and literature review, the researchers confirmed that the species is new to science and named it as Premna caridantha to indicate that the flower of the species superficially looks like a shrimp; especially its incurved corolla tube resembles the back of a shrimp. The new species was published in Phytotaxa

Inflorences of Premna caridantha (Image by TAN Yunhong)

Premna caridantha is a woody climber and has spike-like thyrses. It is most similar to P. grandipaniculata but clearly differs in leaf shape and corolla characters. Its leaf blade is oblong to ovate and the flowers are strongly zygomorphic. The corolla is tube incurved, slightly longer than calyx; the middle lob of the lower lip is with a bright yellowish spot; and the stamens are exerted under the upper lip. 

Premna caridantha is only known from a single locality in tropical montane forests in northern Myanmar, at an elevation of 1,000–1,500 meters. Since no clear picture of its natural distribution or population status was available, the researchers temporarily list the species as Data Deficient (DD) according to the IUCN Red List Categories.

Flowering branch of Premna caridantha (Image by TAN Yunhong)
Habit and habitat of Premna caridantha (Image by TAN Yunhong)

Premna caridantha is the fourth species having spike-like thyrses in Premna and the third new Premna species recently discovered from northern Myanmar,” said TAN Yunhong of XTBG. 

Featured image: Flowering branches of Premna caridantha  (Image by TAN Yunhong)


Reference:

Premna caridantha (Lamiaceae: Permnoideae), a distinct new species from Kachin State, northern Myanmar


Provided by Chinese Academy of Sciences

Pain Differs: Researchers Unveil Distinct Neural Circuits (Neuroscience)

Clinically, multiple lines of evidence show that chronic pain and depressive symptoms are frequently encountered. Patients suffered from both pain and depression are likely to become insensitive to drug treatment, indicating a refractory disease. The neural mechanism under this comorbidity remains unclear.

In a study published in Nature Neuroscience, the research team led by Prof. ZHANG Zhi and Dr. LI Juan from the University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS), reported the discrete thalamocortical circuits underlying the pain symptom caused by tissue injury and depression-like states.

Being the gateway towards cerebral cortex and considered as the major source of ‘nociceptive neurons’ at the highest level of the nervous system in anesthetized animals, the thalamus integrates physical signals of emotions and pains and projects them to the cortex through thalamocortical structure for differentiating and processing. Thus, the thalamocortical circuits for pain processing is a hot spot in research. 

Taking advantage of mouse models of tissue-injury-associated allodynia as well as in vivo calcium imaging and multi-tetrode electrophysiological recordings, the researchers found an enhanced circuit from posterior thalamic nucleus (PO) to primary somatosensory cortex (S1) under tissue-injury conditions, . 

Interestingly, for mice in depression-like states, who also displayed significant allodynia, regulation of the PO -> S1 circuit failed to take effect. What mediates the depression associated pain sensitization is another pathway from the parafascicular thalamic nucleus (PF) to anterior cingulate cortex (ACC).

These results provide a new insight into the pathogenesis of physical pain.

The novel understanding of the neural circuit may add to the precision of these targeting therapy strategies in clinical use as physical intervention of specific brain regions or neural circuits is the current treatment option toward drug-insensitive neurological diseases.

Featured image: Schema of thalamic-cortical neural circuits that produce pain sensitivity to tissue injury and depression. (Image by TANG Haodi et al.)


Reference

Distinct thalamocortical circuits underlie allodynia induced by tissue injury and by depression-like states


Provided by Chinese Academy of Sciences