ACS Publications最新文献

{"title":"Laryngeal Cancer With Lung Metastases Showing Long-Term Complete Response and Delayed Immune-Related Adverse Event After Nivolumab Discontinuation.","authors":"Takahito Kondo, Munehide Nakatsugawa, Mitsuru Okubo, Hironori Nakamura, Daisuke Yunaiyama, Midori Wakiya, Atsuo Takeda, Naiue Kikawada, Takuma Kishida, Miwako Someya, Shigekazu Yoshida, Yasuo Ogawa, Kiyoaki Tsukahara","doi":"10.1177/01455613211031025","DOIUrl":"10.1177/01455613211031025","url":null,"abstract":"<p><p>We report a case of laryngeal cancer with multiple lung metastases that maintained a complete response (CR) for 18 months after discontinuing nivolumab treatment, with colitis developing 5 months after drug discontinuation. A 65-year-old man was diagnosed with T3N2cM0 stage IVA right supraglottic squamous cell carcinoma that progressed after 1 course of TPF (cisplatin, docetaxel, and 5-fluorouracil) as induction chemotherapy. He underwent total laryngectomy, bilateral neck dissection, pharyngeal reconstruction with anterolateral thigh flap, and creation of a permanent tracheostoma; extranodal extension was detected in the right cervical lymph node metastasis, and the patient underwent adjuvant radiotherapy. Multiple lung metastases occurred during radiotherapy, and the patient was deemed platinum refractory; nivolumab treatment was thus initiated. The tumor proportion score for programmed death-ligand 1-evaluated via antibody testing of the laryngeal tumor-was <1. The patient received 240 mg/body nivolumab every 2 weeks; a computed tomography performed after course 16 of nivolumab treatment confirmed a CR. He exhibited grade 2 thyroid dysfunction, grade 1 interstitial pneumonia, and grade 2 colitis after 6, 7, and 14 months of receiving nivolumab, respectively; treatment was discontinued as despite maintaining a CR, interstitial pneumonia occurred twice. Colitis appeared 5 months after nivolumab discontinuation; nevertheless, a CR was maintained after 18 months.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"222-227"},"PeriodicalIF":16.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39199785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Conformational Selection of tRNA^Arg2 by Bacterial Deaminase TadA.","authors":"Jessy Mariam, Sini Porathoor, Ruchi Anand","doi":"10.1021/acs.biochem.4c00649","DOIUrl":"10.1021/acs.biochem.4c00649","url":null,"abstract":"<p><p>Base editing is a common mechanism by which organisms expand their genetic repertoire to access new functions. Here, we explore the mechanism of tRNA recognition in the bacterial deaminase TadA, which exclusively recognizes tRNA^Arg2 and converts the wobble base adenosine (A34) to inosine. We quantitatively evaluate the dynamics of tRNA binding by incorporating the fluorescent adenine analogue 2-aminopurine (2-AP) at position 34 in the wobble base of the anticodon loop. Time-resolved fluorescence and anisotropy studies revealed that the recognition process is finely tuned. Mutations in residues directly involved in facilitating deamination, such as E55A and N42A, showed a minimal impact on binding dynamics. In contrast, mutations in the \"capping residues\", notably R149, unique to prokaryotic TadAs and located 12-15 Å away from the catalytic center, significantly disrupted binding and consequently catalytic activity. The capping residues play a critical role in enabling tRNA recognition, thereby underscoring their importance in enzyme function. Moreover, for effective catalysis, peripheral positively charged residues (R70, R94) that are part of the adjacent subunit in the dimeric assembly are important to splay out the tRNA, assisting in A34 attaining a flipped-out conformation. Perturbations in these extended regions, although 15-20 Å away from the active site, disrupt the binding dynamics and consequently the function, emphasizing the fine regulation of the tRNA recognition process. Analysis reveals that the C-terminal end of the extended helix where R149 is positioned, acts as a selectivity filter imparting exclusivity toward the deamination of tRNA^Arg2 by TadA.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"1530-1540"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Charge, Hydrophobicity, and Lipid Type Drive Antimicrobial Peptides' Unique Perturbation Ensembles.","authors":"Kevin J Cheng, Shashank Shastry, Juan David Campolargo, Michael J Hallock, Taras V Pogorelov","doi":"10.1021/acs.biochem.4c00452","DOIUrl":"10.1021/acs.biochem.4c00452","url":null,"abstract":"<p><p>Antimicrobial peptides (AMPs) have emerged as a promising solution to the escalating public health threat caused by multidrug-resistant bacteria. Although ongoing research efforts have established AMP's role in membrane permeabilization and leakage, the precise mechanisms driving these disruption patterns remain unclear. We leverage molecular dynamics (MD) simulations enhanced by membrane mimetic (HMMM) to systematically investigate how the physiochemical properties of magainin (+3) and pexiganan (+9) affect their localization, insertion, curvature perturbation, and membrane binding ensemble. Building on existing microbiology, NMR, circular dichroism, and fluorescence data, our analysis reveals that the lipid makeup is a key determinant in the binding dynamics and structural conformation of AMPs. We find that phospholipid type is crucial for peptide localization, demonstrated through magainin's predominant interaction with lipid tails and pexiganan's with polar headgroups in POPC/POPS membranes. The membrane curvature changes induced by pexiganan relative to magainin suggest that AMPs with larger charges have more potential in modulating bilayer bending. These insights advance our understanding of AMP-membrane interactions at the molecular level, offering guidance for the design of targeted antimicrobial therapies.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"1484-1500"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coarse-Grained Simulations of Phosphorylation Regulation of p53 Autoinhibition.","authors":"Shrishti Barethiya, Samantha Schultz, Yumeng Zhang, Jianhan Chen","doi":"10.1021/acs.biochem.4c00668","DOIUrl":"10.1021/acs.biochem.4c00668","url":null,"abstract":"<p><p>Intrinsically disordered proteins (IDPs) are key components of cellular signaling and regulatory networks. They frequently remain dynamic even in complexes and thus rely on potentially subtle shifts in the disordered conformational ensemble for function. Understanding the molecular basis of these fascinating mechanisms of IDP function and regulation requires a detailed characterization of dynamic ensembles in various biologically relevant states. Here, we study the phosphorylation dependence of the dynamic interaction between the N-terminal transactivation domain (NTAD) and DNA-binding domain (DBD) of tumor suppressor p53, which plays a key role in the autoinhibition and regulation of p53 activation or termination during various stages of stress response. By extending the hybrid-resolution (HyRes) coarse-grained (CG) protein force field to model phosphorylated side chains, we show that HyRes simulations accurately recapitulate the effects of phosphorylation on the p53 NTAD/DBD interactions. The simulated ensembles show that phosphorylation of Thr55 as well as Ser46 enhances dynamic NTAD/DBD interactions and further induces conformational shifts that promote trans interactions between two p53 dimers to drive dissociation from DNA. These CG simulations thus provide a strong molecular basis in support of previous experimental studies suggesting the central role of dynamic interactions of disordered domains and phosphorylation in the function of p53. The success of this study also suggests that HyRes provides an efficient and viable tool for studying dynamic interactions and post-translational modifications in IDP function and regulation.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"1636-1645"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reimagining Dearomatization: Arenophile-Mediated Single-Atom Insertions and π-Extensions.","authors":"Zohaib Siddiqi, David Sarlah","doi":"10.1021/acs.accounts.5c00035","DOIUrl":"10.1021/acs.accounts.5c00035","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusDearomatization of simple aromatics serves as one of the most direct strategies for converting abundant chemical feedstocks into three-dimensional value-added products. Among such transformations, cycloadditions between arenes and alkenes have historically offered effective means to construct complex polycyclic architectures. However, traditionally harsh conditions, such as high-energy UV light irradiation, have greatly limited the scope of this transformation. Nevertheless, recent progress has led to the development of visible-light-promoted dearomative photocycloadditions with expanded scope capable of preparing complex bicyclic structures.A fundamentally distinct approach to dearomative photocycloadditions involves the visible-light activation of arenophiles, which undergo &lt;i&gt;para&lt;/i&gt;-photocycloaddition with various aromatic compounds to produce arene-arenophile cycloadducts. While only transiently stable and subject to retro-cycloaddition, further functionalization of the photocycloadducts has allowed for the development of a wide collection of dearomatization methodologies that access products orthogonal to existing chemical and biological processes. Central to this strategy was the observation that arene-arenophile photocycloaddition reveals a π-system that can be functionalized through traditional olefin chemistry. Coupled with subsequent [4 + 2]-cycloreversion of the arenophile, this process acts to effectively isolate a single π-system from an aromatic ring. We have developed several transformations that bias this methodology to perform dearomative single-atom insertion and π-extension reactions to prepare unique products that cannot be prepared easily through traditional means.Through the application of a dearomative epoxidation, we were able to develop a method for the epoxidation of arenes and pyridines to arene-oxides and pyridine-oxides, respectively. Notably, when this arenophile chemistry is applied to polycyclic arenes, photocycloaddition reveals a π-system transposed from the site of native olefinic reactivity, enabling unique site-selectivity for dearomative functionalization. As a result, we were able to perform a single-atom insertion of oxygen into polycyclic (aza)arenes to prepare 3-benzoxepines. When applying this strategy in the context of cyclopropanations, we were able to accomplish a dearomative cyclopropanation of polycyclic (aza)arenes which yield benzocycloheptatrienes upon cycloreversion. Notably, while the Buchner ring expansion is a powerful method for the direct single-atom insertion of carbon into arenes, the corresponding cyclopropanation of polycyclic arenes does not yield ring-expanded products. Furthermore, this strategy could be utilized for the synthesis of novel nanographenes through the development of an M-region annulative π-extension (M-APEX) reaction. Traditionally, methods for π-extension rely on the native reactivity of polycyclic aromatics at the K- and bay-region. However, photocy","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"1134-1150"},"PeriodicalIF":16.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BODIPY-Based Photothermal Agent Incorporating Azulene for Enhanced NIR Absorption and Tumor Ablation.","authors":"Kai Nishimura, Mikiya Kato, Tomoya Fukui, Kazuki Miura, Masato Tsuda, Satoshi Okada, Takanori Fukushima, Hiroyuki Nakamura","doi":"10.1021/acs.molpharmaceut.5c00071","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00071","url":null,"abstract":"<p><p>Photothermal therapy (PTT) is a promising minimally invasive treatment that converts light energy into localized heat for tumor ablation. Indocyanine green (ICG), the only clinically approved photothermal agent (PTA), suffers from rapid photobleaching and poor tumor retention, underscoring the urgent need for next-generation PTAs with improved properties. In this study, we report AzuGlu-BODIPY, a novel azulene-containing BODIPY-based PTA incorporating 1,2,3,4-tetrahydroquinoline and glucose, designed to overcome these limitations. AzuGlu-BODIPY demonstrates a high photothermal conversion efficiency (PCE) of 51%, effective near-infrared (NIR) absorption, and thermal stability in both dimethyl sulfoxide (DMSO) and aqueous solutions. <i>In vitro</i> studies revealed potent photothermal efficacy against cancer cell lines, with IC₅₀ values of 3.1-4.6 μM under 808 nm laser irradiation, while <i>in vivo</i> experiments showed complete tumor regression in 4T1 tumor-bearing mice following localized administration and laser treatment. These results suggest AzuGlu-BODIPY as a promising PTA and provide a versatile platform for advancing azulene-based PTAs with enhanced functionality for PTT.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binding Motifs of Doubly and Singly Charged Proton-Bound Clusters of B₁₂F₁₂^2- and Diaminoalkanes.","authors":"Arthur E Lee, Patrick Thomas, Courtney Kates, Terrance B McMahon, W Scott Hopkins","doi":"10.1021/acs.jpca.4c08341","DOIUrl":"https://doi.org/10.1021/acs.jpca.4c08341","url":null,"abstract":"<p><p>The complexation of perfluorinated dodecaborate, B₁₂F₁₂^2-, with protonated diaminoalkanes, [H₂N(CH₂)<i>_n</i>H₂N] (<i>n=</i> 2 - 12), is studied with a combination of infrared multiple photon dissociation (IRMPD) action spectroscopy and ion mobility spectrometry. Singly charged clusters of the form [B₁₂F₁₂ + H₂N(CH₂)<i>_n</i>H₂N + H]^- (<i>n =</i> 2-12) and doubly charged clusters of the form [2B₁₂F₁₂ + H₂N(CH₂)<i>_n</i>H₂N + 2H]^2- (<i>n =</i> 2-12) are observed and characterized experimentally and computationally. For the singly charged clusters, low-energy structural motifs associated with monodentate and bidentate binding motifs of the diaminoalkane are computed via a combination of CREST conformer exploration and density functional theory. For the doubly charged clusters, the doubly protonated diaminoalkane acts as a tether between two B₁₂F₁₂^2- cages. Major product channels of the singly charged and doubly charged species are found to be the formation of HB₁₂F₁₂^- via proton transfer and the loss of B₁₂F₁₂^2-. The fragmentation of HB₁₂F₁₂^- leads to several secondary products, including [B₁₂F₁₁ + N₂]^-. Collision cross sections (CCSs) for the singly charged clusters are reported, and the major subpopulation of the gas phase ensemble for the different singly charged species is the bidentate conformation.</p>","PeriodicalId":59,"journal":{"name":"The Journal of Physical Chemistry A","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Breast Cancer Patient-Specific Metastasis Severity at Bone Site Using <i>In Vitro</i> Models.","authors":"Preetham Ravi, Shrinwanti Ghosh, Pooyan Vahidi Pashaki, Kalidas Shetty, Jiha Kim, Anu Gaba, Dinesh R Katti, Kalpana S Katti","doi":"10.1021/acsbiomaterials.4c01599","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01599","url":null,"abstract":"<p><p>As breast cancer progresses to stage IV, it metastasizes to secondary organs, with a strong propensity for bone colonization. Bone metastasis results in dramatically decreased survival rates and currently lacks a definitive cure. To improve survival rates significantly, there is a need for complex and precise <i>in vitro</i> models that can accurately replicate advanced-stage breast cancer for drug screening purposes. Previously, we established a 3D nanoclay <i>in vitro</i> model of bone metastatic breast cancer using human mesenchymal stem cells in combination with either commercial breast cancer cells (MCF-7 and MDA-MB-231) or patient-derived cells (NT013 and NT023) from the primary breast cancer site. In the present study, the efficacy of the <i>in vitro</i> model to distinguish and differentiate between the severity of metastasis in a total of eight patient-derived cell lines representing various subtypes was evaluated. We also tested the effects of the phytochemically enriched plant extract, <i>Rhodiola crenulata</i><i>, on eight patient-derived cell lines (NT015, NT017, NT021, NT042, NT045, and NT046, in addition to NT013 and NT023)</i> in bone metastatic (BM) culture. Our results confirmed that the cell lines maintained their subtype-specific characteristics after isolation and formed tumors within the bone microenvironment. Additionally, we assessed the impact of these cell lines on Wnt signaling pathways, identifying which lines upregulate or downregulate Wnt signaling through ET-1 and DKK-1 cytokine levels. Within each subtype, we observed differences in the severity of metastasis between patients. <i>R. crenulata</i> induced cytotoxicity in most patient-derived BM cultures, though NT042 BM cultures showed minimal response. In summary, our study has established a patient-derived bone-metastatic breast cancer model that is well-suited for personalized drug screening aimed at treating late-stage breast cancer. This bone metastatic testbed has the capability to evaluate the severity of metastasis within breast cancer subtypes for individual patients.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimuli-Responsive Peptide Liquid Crystals for Tandem Measurements of Residual Chemical Shift Anisotropy and Residual Dipole Coupling in One Sample.","authors":"Jin-Hao He, Yan-Ling Yang, Ai-Qing Zhang, Si-Yong Qin","doi":"10.1021/acs.jpcb.4c08005","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c08005","url":null,"abstract":"<p><p>The combined use of residual chemical shift anisotropy (RCSA) and residual dipolar coupling/residual dipole coupling (RDC) could provide highly complementary information about the structure and relative configuration of unknown organic molecules for their elucidation. However, tandem RCSA and RDC measurements in one sample remain a formidable challenge due to their varied testing requirements. Herein, a stimuli-responsive supramolecular liquid crystal self-assembled from an amphiphilic oligopeptide of C₁₉H₃₉-CONH-VVVVKKK-CONH₂ was constructed, which underwent a phasic transformation from anisotropy to isotropy when subjected to a thermal treatment. Both the anisotropic and isotropic phases exhibited good stability, facilitating tandem measurements of ¹³C-{¹H}-RCSA and (¹³C-¹H)-RDC in one sample with no need for special instruments or correction procedures. We expect that the joint use of RCSAs and RDCs will significantly improve data accuracy and utility for structural and configurational determination of small organic molecules and even biomacromolecules.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A <i>Staphylococcus aureus</i> Virulence Inhibitor Identified by SaeRS Refactoring and Screening in <i>Bacillus subtilis</i>.","authors":"Felix Ekness, Eric A Wold, Catherine S Leasure, Elena Musteata, Andrew J Monteith, Clare Laut, Adriana E Rosato, Eric P Skaar, Jeffrey J Tabor","doi":"10.1021/acssynbio.4c00826","DOIUrl":"https://doi.org/10.1021/acssynbio.4c00826","url":null,"abstract":"<p><p>Bacteria utilize two-component system (TCS) signal transduction pathways to sense environmental and physiological stimuli and mount appropriate responses. In opportunistic pathogens such as <i>Staphylococcus aureus</i>, TCSs activate virulence programs in response to host defense systems. Due to their critical role in pathogenesis, TCSs are important targets for antivirulence drug discovery campaigns. However, challenges associated with screening TCSs in pathogens and <i>in vitro</i> have limited the output of such efforts to a small number of characterized drug candidates. Here, we functionally express the <i>S. aureus</i> virulence-regulating TCS SaeRS from synthetic gene regulatory elements in the model bacterium <i>Bacillus subtilis</i> to reliably screen this system against a small molecule library under simple culturing conditions. Our approach reveals the compound NSC97920 as a strong inhibitor of SaeRS signaling. We combine <i>in situ</i>, <i>in vivo</i>, <i>in silico,</i> and <i>in vitro</i> characterization to demonstrate that NSC97920 suppresses the critical step of autophosphorylation in the SaeS histidine kinase, resulting in strong antivirulence activity. Our work shows that heterologous expression and screening of TCSs in model bacteria could accelerate the development of therapeutics against antibiotic-resistant pathogens.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}