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1.
Sci Adv ; 10(28): eadl6280, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996018

RESUMO

H3K4 methylation by Set1-COMPASS (complex of proteins associated with Set1) is a conserved histone modification. Although it is critical for gene regulation, the posttranslational modifications of this complex that affect its function are largely unexplored. This study showed that N-terminal acetylation of Set1-COMPASS proteins by N-terminal acetyltransferases (NATs) can modulate H3K4 methylation patterns. Specifically, deleting NatA substantially decreased global H3K4me3 levels and caused the H3K4me2 peak in the 5' transcribed regions to shift to the promoters. NatA was required for N-terminal acetylation of three subunits of Set1-COMPASS: Shg1, Spp1, and Swd2. Moreover, deleting Shg1 or blocking its N-terminal acetylation via proline mutation of the target residue drastically reduced H3K4 methylation. Thus, NatA-mediated N-terminal acetylation of Shg1 shapes H3K4 methylation patterns. NatB also regulates H3K4 methylation, likely via N-terminal acetylation of the Set1-COMPASS protein Swd1. Thus, N-terminal acetylation of Set1-COMPASS proteins can directly fine-tune the functions of this complex, thereby substantially shaping H3K4 methylation patterns.


Assuntos
Histona-Lisina N-Metiltransferase , Histonas , Proteínas de Saccharomyces cerevisiae , Acetilação , Histonas/metabolismo , Metilação , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Processamento de Proteína Pós-Traducional , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética
2.
Virulence ; 15(1): 2367648, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38899601

RESUMO

The emergence of multidrug-resistant bacteria poses a significant threat to human health, necessitating a comprehensive understanding of their underlying mechanisms. Uropathogenic Escherichia coli (UPEC), the primary causative agent of urinary tract infections, is frequently associated with multidrug resistance and recurrent infections. To elucidate the mechanism of resistance of UPEC to beta-lactam antibiotics, we generated ampicillin-resistant UPEC strains through continuous exposure to low and high levels of ampicillin in the laboratory, referred to as Low AmpR and High AmpR, respectively. Whole-genome sequencing revealed that both Low and High AmpR strains contained mutations in the marR, acrR, and envZ genes. The High AmpR strain exhibited a single additional mutation in the nlpD gene. Using protein modeling and qRT-PCR analyses, we validated the contributions of each mutation in the identified genes to antibiotic resistance in the AmpR strains, including a decrease in membrane permeability, increased expression of multidrug efflux pump, and inhibition of cell lysis. Furthermore, the AmpR strain does not decrease the bacterial burden in the mouse bladder even after continuous antibiotic treatment in vivo, implicating the increasing difficulty in treating host infections caused by the AmpR strain. Interestingly, ampicillin-induced mutations also result in multidrug resistance in UPEC, suggesting a common mechanism by which bacteria acquire cross-resistance to other classes of antibiotics.


Assuntos
Ampicilina , Antibacterianos , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli , Mutação , Infecções Urinárias , Escherichia coli Uropatogênica , Escherichia coli Uropatogênica/genética , Escherichia coli Uropatogênica/efeitos dos fármacos , Animais , Farmacorresistência Bacteriana Múltipla/genética , Infecções Urinárias/microbiologia , Infecções por Escherichia coli/microbiologia , Camundongos , Antibacterianos/farmacologia , Ampicilina/farmacologia , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Feminino , Humanos , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma
3.
BMC Biol ; 22(1): 105, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702628

RESUMO

BACKGROUND: Histone H3K4 tri-methylation (H3K4me3) catalyzed by Set1/COMPASS, is a prominent epigenetic mark found in promoter-proximal regions of actively transcribed genes. H3K4me3 relies on prior monoubiquitination at the histone H2B (H2Bub) by Rad6 and Bre1. Swd2/Cps35, a Set1/COMPASS component, has been proposed as a key player in facilitating H2Bub-dependent H3K4me3. However, a more comprehensive investigation regarding the relationship among Rad6, Swd2, and Set1 is required to further understand the mechanisms and functions of the H3K4 methylation. RESULTS: We investigated the genome-wide occupancy patterns of Rad6, Swd2, and Set1 under various genetic conditions, aiming to clarify the roles of Set1 and Rad6 for occupancy of Swd2. Swd2 peaks appear on both the 5' region and 3' region of genes, which are overlapped with its tightly bound two complexes, Set1 and cleavage and polyadenylation factor (CPF), respectively. In the absence of Rad6/H2Bub, Set1 predominantly localized to the 5' region of genes, while Swd2 lost all the chromatin binding. However, in the absence of Set1, Swd2 occupancy near the 5' region was impaired and rather increased in the 3' region. CONCLUSIONS: This study highlights that the catalytic activity of Rad6 is essential for all the ways of Swd2's binding to the transcribed genes and Set1 redistributes the Swd2 to the 5' region for accomplishments of H3K4me3 in the genome-wide level.


Assuntos
Histona-Lisina N-Metiltransferase , Histonas , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Histonas/metabolismo , Histonas/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Metilação , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/genética
4.
Angew Chem Int Ed Engl ; 63(15): e202401097, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38308505

RESUMO

It is highly challenging to reproducibly prepare semiconducting polymers with targeted molecular weight tailored for next-generation photovoltaic applications. Once such an easily accessible methodology is established, which can not only contribute to overcome the current limitation of the statistically determined nature of semiconducting polymers, but also facilitate rapid incorporation into the broad synthetic chemists' toolbox. Here, we describe a simple yet robust ultrasonication-assisted Stille polymerization for accessing semiconducting polymers with high-precision tailored molecular weights (from low to ultrahigh molecular weight ranges) while mitigating their interbatch variations. We propose that ultrasound-induced simultaneous physical and chemical events enable precise control of the semiconducting polymers' molecular weights with high reproducibility to satisfy all the optical/electrical and morphological demands of diverse types of high-performance semiconducting polymer-based devices; as demonstrated in in-depth experimental screenings in applications of both organic and perovskite photovoltaics. We believe that this methodology provides a fast development of new and existing semiconducting polymers with the highest-level performances possible on various photovoltaic devices.

5.
R Soc Open Sci ; 11(1): 231129, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38204788

RESUMO

The gut mycobiome plays an important role in the health and disease of the human gut, but its exact function is still under investigation. While there is a wealth of information available on the bacterial community of the human gut microbiome, research on the fungal community is still relatively limited. In particular, technical methodologies for mycobiome analysis, especially the DNA extraction method for human faecal samples, varied in different studies. In the current study, two commercial kits commonly used in DNA extraction, the QIAamp® Fast DNA Stool Mini Kit and DNeasy PowerSoil Pro Kit, and one manual method, the International Human Microbiome Standards Protocol Q, were compared. Furthermore, the effectiveness of two different bead-beating machines, the Mini-Beadbeater-16 and FastPrep-24TM 5G, was compared in parallel. A mock fungal community with a known composition of fungal strains was also generated and included to compare different DNA extraction methods. Our results suggested that the method using the DNeasy PowerSoil Pro Kit and Mini-Beadbeater-16 provides the best results to extract DNA from human faecal samples. Based on our data, we propose a standard operating procedure for DNA extraction from human faecal samples for mycobiome analysis.

6.
Adv Mater ; 35(52): e2306092, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37739451

RESUMO

Conversion of sunlight and organic carbon substrates to sustainable energy sources through microbial metabolism has great potential for the renewable energy industry. Despite recent progress in microbial photosynthesis, the development of microbial platforms that warrant efficient and scalable fuel production remains in its infancy. Efficient transfer and retrieval of gaseous reactants and products to and from microbes are particular hurdles. Here, inspired by water lily leaves floating on water, a microbial device designed to operate at the air-water interface and facilitate concomitant supply of gaseous reactants, smooth capture of gaseous products, and efficient sunlight delivery is presented. The floatable device carrying Rhodopseudomonas parapalustris, of which nitrogen fixation activity is first determined through this study, exhibits a hydrogen production rate of 104 mmol h-1  m-2 , which is 53 times higher than that of a conventional device placed at a depth of 2 cm in the medium. Furthermore, a scaled-up device with an area of 144 cm2 generates hydrogen at a high rate of 1.52 L h-1  m-2 . Efficient nitrogen fixation and hydrogen generation, low fabrication cost, and mechanical durability corroborate the potential of the floatable microbial device toward practical and sustainable solar energy conversion.

7.
J Microbiol ; 61(7): 663-672, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37615929

RESUMO

Subtercola boreus K300T is a novel psychrophilic strain that was isolated from permanently cold groundwater in Finland and has also been found in several places in Antarctica including lake, soil, and rocks. We performed genomic and transcriptomic analyses of 5 strains from Antarctica and a type strain to understand their adaptation to different environments. Interestingly, the isolates from rocks showed a low growth rate and smaller genome size than strains from the other isolation sources (lake, soil, and groundwater). Based on these habitat-dependent characteristics, the strains could be classified into two ecotypes, which showed differences in energy production, signal transduction, and transcription in the clusters of orthologous groups of proteins (COGs) functional category. In addition, expression pattern changes revealed differences in metabolic processes, including uric acid metabolism, DNA repair, major facilitator superfamily (MFS) transporters, and xylose degradation, depending on the nutritional status of their habitats. These findings provide crucial insights into the environmental adaptation of bacteria, highlighting genetic diversity and regulatory mechanisms that enable them to thrive in the cryosphere.


Assuntos
Actinomycetales , Bactérias/genética , Aclimatação , Regiões Antárticas , Reparo do DNA
8.
Angew Chem Int Ed Engl ; 62(39): e202308267, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37539636

RESUMO

Single-component organic solar cells (SCOSCs) based on conjugated block copolymers (CBCs) by covalently bonding a polymer donor and polymer acceptor become more and more appealing due to the formation of a favorable and stable morphology. Unfortunately, a deep understanding of the effect of the assembly behavior caused by the sequence structure of CBCs on the device performance is still missing. Herein, from the aspect of manipulating the sequence length and distribution regularity of CBCs, we synthesized a series of new CBCs, namely D18(20)-b-PYIT, D18(40)-b-PYIT and D18(60)-b-PYIT by two-pot polymerization, and D18(40)-b-PYIT(r) by traditional one-pot method. It is observed that precise manipulation of sequence length and distribution regularity of the polymer blocks fine-tunes the self-assembly of the CBCs, optimizes film morphology, improves optoelectronic properties, and reduces energy loss, leading to simultaneously improved efficiency and stability. Among these CBCs, the D18(40)-b-PYIT-based device achieves a high efficiency of 13.4 % with enhanced stability, which is an outstanding performance among SCOSCs. Importantly, the regular sequence distribution and suitable sequence length of the CBCs enable a facile film-forming process of the printed device. For the first time, the blade-coated large-area rigid/flexible SCOSCs are fabricated, delivering an impressive efficiency of 11.62 %/10.73 %, much higher than their corresponding binary devices.

9.
ACS Appl Mater Interfaces ; 15(33): 39636-39646, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37579241

RESUMO

Alongside high power conversion efficiencies (PCEs), device stability, especially thermal issues, is another key factor for the successful commercialization of nonfullerene acceptor (NFA)-based organic solar cells (OSCs). Considering the significant effects of the side-chain engineering of NFAs on molecular packing and/or locking strongly associated with the thermal stability of OSCs, herein, we present two new isomeric NFAs with 4-fluoro- and 2-fluoro-substituted hexylphenyl two-dimensional (2D) outer side chains (4FY and 2FY, respectively). In contrast with the 2FY having a horizontal stretching conformation, 4FY exhibits a diagonal stretching conformation of the 2D outer side chains and a higher dipole moment, resulting in a huge difference in their crystalline/aggregation characteristics, i.e., 4FY possesses a higher crystallinity with a denser molecular packing than the 2FY neat film, as evidenced by thermal and morphological characterizations. Encouragingly, relative to the one based on 2FY, the OSC based on 4FY delivers a PCE as high as 16.4%, together with excellent thermal stability (88.4% PCE retention under 85 °C for 360 h), which is attributed to a more optimal and robust blend morphology induced by its better compatibility into the used donor component and stronger crystallinity. This work demonstrates that in addition to the improved photovoltaic property, the appropriate F-positioning on the 2D outer side chains can play a key role in controlling their conformations, which can promote the increase of the thermal stability of OSCs.

10.
Biotechnol Biofuels Bioprod ; 16(1): 114, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37464261

RESUMO

BACKGROUND: Methanotrophs have emerged as promising hosts for the biological conversion of methane into value-added chemicals, including various organic acids. Understanding the mechanisms of acid tolerance is essential for improving organic acid production. WatR, a LysR-type transcriptional regulator, was initially identified as involved in lactate tolerance in a methanotrophic bacterium Methylomonas sp. DH-1. In this study, we investigated the role of WatR as a regulator of cellular defense against weak organic acids and identified novel target genes of WatR. RESULTS: By conducting an investigation into the genome-wide binding targets of WatR and its role in transcriptional regulation, we identified genes encoding an RND-type efflux pump (WatABO pump) and previously unannotated small open reading frames (smORFs), watS1 to watS5, as WatR target genes activated in response to acetate. The watS1 to watS5 genes encode polypeptides of approximately 50 amino acids, and WatS1 to WatS4 are highly homologous with one predicted transmembrane domain. Deletion of the WatABO pump genes resulted in decreased tolerance against formate, acetate, lactate, and propionate, suggesting its role as an efflux pump for a wide range of weak organic acids. WatR repressed the basal expression of watS genes but activated watS and WatABO pump genes in response to acetate stress. Overexpression of watS1 increased tolerance to acetate but not to other acids, only in the presence of the WatABO pump. Therefore, WatS1 may increase WatABO pump specificity toward acetate, switching the general weak acid efflux pump to an acetate-specific efflux pump for efficient cellular defense against acetate stress. CONCLUSIONS: Our study has elucidated the role of WatR as a key transcription factor in the cellular defense against weak organic acids, particularly acetate, in Methylomonas sp. DH-1. We identified the genes encoding WatABO efflux pump and small polypeptides (WatS1 to WatS5), as the target genes regulated by WatR for this specific function. These findings offer valuable insights into the mechanisms underlying weak acid tolerance in methanotrophic bacteria, thereby contributing to the development of bioprocesses aimed at converting methane into value-added chemicals.

11.
Phys Chem Chem Phys ; 25(25): 17001-17009, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37337735

RESUMO

All-polymer solar cells (all-PSCs), based on p-type polymer donors and n-type acceptors as the active layer, offer exceptional promise because of excellent thermal stability, superior film formation, and good mechanical stress as a unique bulk heterojunction (BHJ) solar cell combination. Therefore, tuning the molecular composition between polymers is crucial for optimizing power conversion efficiency (PCE) in these all-PSC systems. In this study, we synthesized a series of naphthalene diimide (NDI)-based random terpolymers P(NDI-BDD10), P(NDI-TPD10), P(NDI-TT10), and P(NDI-2FQ10) with axisymmetric (BDD, TPD) and asymmetric (TT, 2FQ) electron acceptors. Compared with the blend morphology of PBDB-T:N2200, their diverse effects due to the addition of trace amounts of axisymmetric and asymmetric components were comprehensively investigated using physical and surface analyses and structural simulations. Consequently, most of our polymer acceptors demonstrated improved fill factors (FFs) in the optimal morphology. P(NDI-BDD10)-based devices achieved the highest PCE of 6.80% and FF of 69.1%, while the architecturally most asymmetric P(NDI-TT10)-based devices reached the lowest PCE of 4.52% despite an enhanced FF of 65.4%. As a result, the appropriate molecular arrangement is crucial for obtaining the desired morphology and improved PCE. Our findings give novel molecular design insight into the distinctions between axisymmetric and asymmetric electron acceptors and seem significant for achieving improved morphological features and efficiency.

12.
Chemistry ; 29(45): e202300653, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37191934

RESUMO

Realizing efficient all-polymer solar cell (APSC) acceptors typically involves increased building block synthetic complexity, hence potentially unscalable syntheses and/or prohibitive costs. Here we report the synthesis, characterization, and implementation in APSCs of three new polymer acceptors P1-P3 using a scalable donor fragment, bis(2-octyldodecyl)anthra[1,2-b : 5,6-b']dithiophene-4,10-dicarboxylate (ADT) co-polymerized with the high-efficiency acceptor units, NDI, Y6, and IDIC. All three copolymers have comparable photophysics to known polymers; however, APSCs fabricated by blending P1, P2 and P3 with donor polymers PM5 and PM6 exhibit modest power conversion efficiencies (PCEs), with the champion P2-based APSC achieving PCE=5.64 %. Detailed morphological and microstructural analysis by AFM and GIWAXS reveal a non-optimal APSC active layer morphology, which suppresses charge transport. Despite the modest efficiencies, these APSCs demonstrate the feasibility of using ADT as a scalable and inexpensive electron rich/donor building block for APSCs.

13.
Small ; 19(27): e2300507, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37010009

RESUMO

Both organic solar cells (OSCs) and organic thermoelectrics (OTEs) are promising energy-harvesting technologies for future renewable and sustainable energy sources. Among various material systems, organic conjugated polymers are an emerging material class for the active layers of both OSCs and OTEs. However, organic conjugated polymers showing both OSC and OTE properties are rarely reported because of the different requirements toward the OSCs and OTEs. In this study, the first simultaneous investigation of the OSC and OTE properties of a wide-bandgap polymer PBQx-TF and its backbone isomer iso-PBQx-TF are reported. All wide-bandgap polymers form face-on orientations in a thin-film state, but PBQx-TF has more of a crystalline character than iso-PBQx-TF, originating from the backbone isomeric structures of α,α '/ß,ß '-connection between two thiophene rings. Additionally, iso-PBQx-TF shows inactive OSC and poor OTE properties, probably because of the absorption mismatch and unfavorable molecular orientations. At the same time, PBQx-TF exhibits both decent OSC and OTE performances, indicating that it satisfies the requirements for both OSCs and OTEs. This study presents the OSC and OTE dual-functional energy-harvesting wide-bandgap polymer and the future research directions for hybrid energy-harvesting materials.

14.
Front Immunol ; 14: 1064900, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36793721

RESUMO

Objectives: To investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events. Methods: First, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated propionate-deficient mutant bacteria. Short-chain fatty acids were measured in the bacterial culture supernatant, serum, feces, and cecum contents using gas chromatography-mass spectrometry. Mice fed with candidate and mutant bacteria were subjected to inflammatory arthritis. Results: Contrary to expectations, the mice treated with DSS exhibited fewer symptoms of inflammatory arthritis. Intriguingly, the gut microbiota contributes, at least in part, to the improvement of colitis-mediated arthritis. Among the altered microorganisms, Bacteroides vulgatus and its higher taxonomic ranks were enriched in the DSS-treated mice. B. vulgatus, B. caccae, and B. thetaiotaomicron exerted anti-arthritic effects. Propionate production deficiency further prevented the protective effect of B. thetaiotaomicron on arthritis. Conclusions: We suggest a novel relationship between the gut and joints and an important role of the gut microbiota as communicators. Moreover, the propionate-producing Bacteroides species examined in this study may be a potential candidate for developing effective treatments for inflammatory arthritis.


Assuntos
Colite , Propionatos , Camundongos , Animais , Propionatos/farmacologia , RNA Ribossômico 16S/genética , Colite/patologia , Fezes/microbiologia , Bactérias/genética , Bacteroides/genética
15.
ACS Appl Mater Interfaces ; 15(1): 1629-1638, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36592389

RESUMO

Organic electrochemical transistors (OECTs) have enormous potential for use in biosignal amplifiers, analyte sensors, and neuromorphic electronics owing to their exceptionally large transconductance. However, it is challenging to simultaneously achieve high charge carrier mobility and volumetric capacitance, the two most important figures of merit in OECTs. Herein, a method of achieving high-performance OECT with donor-acceptor conjugated copolymers by introducing fluorine units is proposed. A series of cyclopentadithiophene-benzothiadiazole (CDT-BT) copolymers for use in high-performance OECTs with enhanced charge carrier mobility (from 0.65 to 1.73 cm2·V-1·s-1) and extended volumetric capacitance (from 44.8 to 57.6 F·cm-3) by fluorine substitution is achieved. The increase in the volumetric capacitance of the fluorinated polymers is attributed to either an increase in the volume at which ions can enter the film or a decrease in the effective distance between the ions and polymer backbones. The fluorine substitution increases the backbone planarity of the CDT-BT copolymers, enabling more efficient charge carrier transport. The fluorination strategy of this work suggests the more versatile use of conjugated polymers for high-performance OECTs.

16.
Small ; 19(12): e2206233, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36592416

RESUMO

Albeit considerable attention to the fast-developing organic thermoelectric (OTE) materials due to their flexibility and non-toxic features, it is still challenging to design an OTE polymer with superior thermoelectric properties. In this work, two "isomorphic" donor-acceptor (D-A) conjugated polymers are studied as the semiconductor in OTE devices, revealing for the first time the internal mechanism of regioregularity on thermoelectric performances in D-A type polymers. A higher molecular structure regularity can lead to higher crystalline order and mobility, higher doping efficiency, order of energy state, and thermoelectric (TE) performance. As a result, the regioregular P2F exhibits a maximum power factor (PF) of up to 113.27 µW m-1  K-2 , more than three times that of the regiorandom PRF (35.35 µW m-1  K-2 ). However, the regular backbone also implies lower miscibility with a dopant, negatively affecting TE performance. Therefore, the trade-off between doping efficiency and miscibility plays a vital role in OTE materials, and this work sheds light on the molecular design strategy of OTE polymers with state-of-the-art performances.

17.
J Microbiol Biotechnol ; 33(3): 319-328, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36697229

RESUMO

Malassezia and Staphylococcus are the most dominant genera in human skin microbiome. To explore the inter-kingdom interactions between the two genera, we examined the transcriptional changes in Malassezia and Staphylococcus species induced upon co-culturing. RNA-seq analyses revealed that genes encoding ribosomal proteins were upregulated, while those encoding aspartyl proteases were downregulated in M. restricta after co-culturing with Staphylococcus species. We identified MRET_3770 as a major secretory aspartyl protease coding gene in M. restricta through pepstatin-A affinity chromatography followed by mass spectrometry and found that the expression of MRET_3770 was significantly repressed upon co-culturing with Staphylococcus species or by incubation in media with reduced pH. Moreover, biofilm formation by Staphylococcus aureus was inhibited in the spent medium of M. restricta, suggesting that biomolecules secreted by M. restricta such as secretory aspartyl proteases may degrade the biofilm structure. We also examined the transcriptional changes in S. aureus co-cultured with M. restricta and found co-cultured S. aureus showed increased expression of genes encoding ribosomal proteins and downregulation of those involved in riboflavin metabolism. These transcriptome data of co-cultured fungal and bacterial species demonstrate a dynamic interplay between the two co-existing genera.


Assuntos
Ácido Aspártico Proteases , Malassezia , Humanos , Malassezia/genética , Staphylococcus , Staphylococcus aureus/genética , Pele/microbiologia , Ácido Aspártico Proteases/genética , Ácido Aspártico Endopeptidases , Proteínas Ribossômicas
18.
Immunology ; 168(3): 493-510, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36183156

RESUMO

Not only are many Mycobacteria pathogens, but they can act as strong non-specific immunopotentiators, generating beneficial effects on the pathogenesis of some diseases. However, there has been no direct evidence of the effect of mycobacterial species on colorectal cancer (CRC). Herein, we showed that there may be a meaningful inverse correlation between the incidence of tuberculosis and CRC based on global statistics and that heat-killed Mycobacterial tuberculosis and live Mycobacterium bovis (Bacillus Calmette-Guérin strain) could ameliorate CRC development. In particular, using a faecal microbiota transplantation and a comparison between separate housing and cohousing, we demonstrated that the gut microbiota is involved in the protective effects. The microbial alterations can be elucidated by the modulation of antimicrobial activities including those of the Reg3 family genes. Furthermore, interleukin-22 production by T helper cells contributed to the anti-inflammatory activity of Mycobacteria. Our results revealed a novel role of Mycobacteria involving gut microbial alterations in dampening inflammation-associated CRC and an immunological mechanism underlying the interaction between microbes and host immunity.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Mycobacterium bovis , Mycobacterium tuberculosis , Tuberculose , Humanos , Vacina BCG
19.
NPJ Biofilms Microbiomes ; 8(1): 65, 2022 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-35987769

RESUMO

In addition to catalyzing coupled transport and phosphorylation of carbohydrates, the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) regulates various physiological processes in most bacteria. Therefore, the transcription of genes encoding the PTS is precisely regulated by transcriptional regulators depending on substrate availability. As the distribution of the mannose-specific PTS (PTSMan) is limited to animal-associated bacteria, it has been suggested to play an important role in host-bacteria interactions. In Vibrio cholerae, mannose is known to inhibit biofilm formation. During host infection, the transcription level of the V. cholerae gene encoding the putative PTSMan (hereafter referred to as manP) significantly increases, and mutations in this gene increase host survival rate. Herein, we show that an AraC-type transcriptional regulator (hereafter referred to as ManR) acts as a transcriptional activator of the mannose operon and is responsible for V. cholerae growth and biofilm inhibition on a mannose or fructose-supplemented medium. ManR activates mannose operon transcription by facilitating RNA polymerase binding to the promoter in response to mannose 6-phosphate and, to a lesser extent, to fructose 1-phosphate. When manP or manR is impaired, the mannose-induced inhibition of biofilm formation was reversed and intestinal colonization was significantly reduced in a Drosophila melanogaster infection model. Our results show that ManR recognizes mannose and fructose in the environment and facilitates V. cholerae survival in the host.


Assuntos
Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato , Vibrio cholerae , Animais , Citarabina , Drosophila melanogaster/metabolismo , Frutose , Regulação Bacteriana da Expressão Gênica , Humanos , Manose/metabolismo , Fosfatos/metabolismo , Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/genética , Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/metabolismo , Vibrio cholerae/genética , Vibrio cholerae/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-35849798

RESUMO

Modifying the end-capping groups in nonfullerene acceptors (NFAs) is an effective strategy for modulating their properties and that of the entire NFAs. This study reports the synthesis of a novel γ-ester-functionalized IC end-capping group (IC-γe) and its incorporation into the benzothiadiazole-fused central core, yielding isomer-free IC-γe end-capped NFAs, such as Y-IC-γe, Y-FIC-γe, and Y-ClIC-γe. The resultant NFAs exhibited similar absorption profiles but upshifted the lowest unoccupied molecular orbital energy level compared with those of the ester-free analogues, such as Y6 and Y7. Without thermal annealing, an excellent power conversion efficiency (PCE) of 16.4% is realized in the annealing-free OSC based on Y-FIC-γe with the PM6 donor polymer, which outperforms the OSCs based on Y-IC-γe and Y-ClIC-γe. In addition, the OSCs based on asymmetric Y-FIC-γe and Y-ClIC-γe have higher thermal stability with more than 83% PCE retention at an elevated temperature after 456 h than the symmetric Y-IC-γe case. In this study, we not only establish the structure-property relationship regarding the ester functionality and symmetricity tuning on the NFAs but also diagnose the reasons for the best-performing Y-FIC-γe-based OSCs, providing useful information for a novel high-performing NFA design strategy.

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