ACS Infectious Diseases最新文献

{"title":"Breaking Down the Barriers of Drug Resistance and Corneal Permeability with Chitosan-Poly(ethylene glycol)-LK₁₃ Peptide Conjugate to Combat Fungal Keratitis.","authors":"Ning Gao, Xiaoyan Ju, Xiting Jiao, Yuanyuan Qi, Ye Tian, Shidong Jiang, Zhongwei Niu, Shaozhen Zhao, Ruibo Yang","doi":"10.1021/acsinfecdis.4c00288","DOIUrl":"10.1021/acsinfecdis.4c00288","url":null,"abstract":"<p><p>Fungal keratitis (FK) is a leading cause of preventable blindness and eye loss. The poor antifungal activity, increased drug resistance, limited corneal permeability, and unsatisfactory biosafety of conventional antifungal eye drops are among the majority of the challenges that need to be addressed for currently available antifungal drugs. Herein, this study proposes an effective strategy that employs chitosan-poly(ethylene glycol)-LK₁₃ peptide conjugate (CPL) in the treatment of FK. Nanoassembly CPL can permeate the lipophilic corneal epithelium in the transcellular route, and its hydrophilicity surface is a feature to drive its permeability through hydrophilic stroma. When encountering fungal cell membrane, CPL dissembles and exposes the antimicrobial peptide (LK₁₃) to destroy fungal cell membranes, the minimum inhibitory concentration values of CPL against <i>Fusarium solani</i> (<i>F. solani</i>) are always not to exceed 8 μg peptide/mL before and after drug resistance induction. In a rat model of <i>Fusarium</i> keratitis, CPL demonstrates superior therapeutic efficacy than commercially available natamycin ophthalmic suspension. This study provides more theoretical and experimental supports for the application of CPL in the treatment of FK.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588885","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":"Challenges and Opportunities with Antibiotic Discovery and Exploratory Research.","authors":"Laura J V Piddock, Rohit Malpani, Alan Hennessy","doi":"10.1021/acsinfecdis.4c00530","DOIUrl":"10.1021/acsinfecdis.4c00530","url":null,"abstract":"<p><p>Discovery and exploratory research can identify new antibiotics and biological targets. However, failure rates are high, and funding is insufficient to solve the scientific challenges and attract researchers to antibacterial R&D. Novel methods, including artificial intelligence, have been applied to early-stage research, but these have yet to deliver new antibiotics. The Global Antibiotic Research & Development Partnership (GARDP) is investing in discovery and exploratory research and an R&D education and outreach program. GARDP's efforts, including application of novel R&D methods and new global networks of R&D researchers to develop new antibiotics, is helping address antimicrobial resistance sustainably over the long-term.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141746714","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":"Pilot-Scale Screening of Clinically Approved Drugs to Identify Uridine Insertion/Deletion RNA Editing Inhibitors in Trypanosoma brucei","authors":"Mojtaba Rostamighadi,&nbsp;Arezou Kamelshahroudi,&nbsp;Vanessa Pitsitikas,&nbsp;Kenneth A. Jacobson and Reza Salavati*,&nbsp;","doi":"10.1021/acsinfecdis.4c0039410.1021/acsinfecdis.4c00394","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00394https://doi.org/10.1021/acsinfecdis.4c00394","url":null,"abstract":"<p >RNA editing pathway is a validated target in kinetoplastid parasites (<i>Trypanosoma brucei</i>, <i>Trypanosoma cruzi</i>, and <i>Leishmania</i> spp.) that cause severe diseases in humans and livestock. An essential large protein complex, the editosome, mediates uridine insertion and deletion in RNA editing through a stepwise process. This study details the discovery of editosome inhibitors by screening a library of widely used human drugs using our previously developed <i>in vitro</i> biochemical Ribozyme Insertion Deletion Editing (RIDE) assay. Subsequent studies on the mode of action of the identified hits and hit expansion efforts unveiled compounds that interfere with RNA-editosome interactions and novel ligase inhibitors with IC₅₀ values in the low micromolar range. Docking studies on the ligase demonstrated similar binding characteristics for ATP and our novel epigallocatechin gallate inhibitor. The inhibitors demonstrated potent trypanocidal activity and are promising candidates for drug repurposing due to their lack of cytotoxic effects. Further studies are necessary to validate these targets using more definitive gene-editing techniques and to enhance the safety profile.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142228412","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":"Progranulin Protects against <i>Aspergillus fumigatus</i> Keratitis by Attenuating the Inflammatory Response through Enhancing Autophagy.","authors":"Pingli Qi, Xing Liu, Cui Li, Qiang Xu, Liting Hu, Huijin Duan, Guiqiu Zhao, Jing Lin","doi":"10.1021/acsinfecdis.4c00236","DOIUrl":"10.1021/acsinfecdis.4c00236","url":null,"abstract":"<p><p>Fungal keratitis (FK) is a severe corneal condition caused by pathogenic fungi and is associated with the virulence of fungi and an excessive tissue inflammatory response. Progranulin (PGRN), functioning as a multifunctional growth factor, exerts a pivotal influence on the regulation of inflammation and autophagy. The aim of our research was to analyze the role of PGRN in <i>Aspergillus fumigatus</i> (<i>A. fumigatus</i>) keratitis. We found that PGRN expression was increased in the mouse cornea with <i>A. fumigatus</i> keratitis. In our experiments, corneas of mice with FK were treated with 100 ng/mL of PGRN. In vitro, RAW 264.7 cells were treated with 10 ng/mL of PGRN before <i>A. fumigatus</i> stimulation. The findings suggested that PGRN effectively alleviated corneal edema and decreased the expression of pro-inflammatory cytokines in mice. In stimulated RAW 264.7 cells, PGRN treatment suppressed the expression of pro-inflammatory cytokines IL-6 and TNF-α but promoted the expression of the anti-inflammatory cytokines IL-10. PGRN treatment significantly upregulated the expression of autophagy-related proteins LC3, Beclin-1, and Atg-7. 3-Methyladenine (3-MA, autophagy inhibitor) reversed the regulation of inflammatory cytokines by PGRN. In addition, our study demonstrated that PGRN also enhanced phagocytosis in RAW 264.7 cells. In summary, PGRN attenuated the inflammatory response of <i>A. fumigatus</i> keratitis by increasing autophagy and enhanced the phagocytic activity of RAW 264.7 cells. This showed that PGRN had a protective effect on <i>A. fumigatus</i> keratitis.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430845","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":"Isobavachalcone Exhibits Potent Antifungal Efficacy by Inhibiting Enolase Activity and Glycolysis in <i>Candida albicans</i>.","authors":"Hao Wu, Zhe Ji, Xin Huang, Liping Li, Sijin Hang, Jinhua Yu, Hui Lu, Yuanying Jiang","doi":"10.1021/acsinfecdis.4c00399","DOIUrl":"10.1021/acsinfecdis.4c00399","url":null,"abstract":"<p><p>Invasive fungal diseases (IFDs) are becoming increasingly acknowledged as a significant concern linked to heightened rates of morbidity and mortality. Regrettably, the available antifungal therapies for managing IFDs are constrained. Emerging evidence indicates that enolase holds promise as a potential target protein for combating IFDs; however, there is currently a deficiency in antifungal medications specifically targeting enolase. This study establishes that isobavachalcone (IBC) exhibits noteworthy antifungal efficacy both in vitro and in vivo. Moreover, our study has demonstrated that IBC effectively targets Eno1 in <i>Candida albicans</i> (CaEno1), resulting in the suppression of the glycolytic pathway. Additionally, our research has indicated that IBC exhibits a higher affinity for CaEno1 compared to human Eno1 (hEno1), with the presence of isoprenoid in the side chain of IBC playing a crucial role in its ability to inhibit enolase activity. These findings contribute to the comprehension of antifungal approaches that target Eno1, identifying IBC as a potential inhibitor of Eno1 in human pathogenic fungi.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597896","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":"An Engineered N-Glycosylated Dengue Envelope Protein Domain III Facilitates Epitope-Directed Selection of Potently Neutralizing and Minimally Enhancing Antibodies.","authors":"Napon Nilchan, Romchat Kraivong, Prasit Luangaram, Anunyaporn Phungsom, Mongkhonphan Tantiwatcharakunthon, Somchoke Traewachiwiphak, Tanapan Prommool, Nuntaya Punyadee, Panisadee Avirutnan, Thaneeya Duangchinda, Prida Malasit, Chunya Puttikhunt","doi":"10.1021/acsinfecdis.4c00058","DOIUrl":"10.1021/acsinfecdis.4c00058","url":null,"abstract":"<p><p>The envelope protein of dengue virus (DENV) is a primary target of the humoral immune response. The domain III of the DENV envelope protein (EDIII) is known to be the target of multiple potently neutralizing antibodies. One such antibody is 3H5, a mouse antibody that binds strongly to EDIII and potently neutralizes DENV serotype 2 (DENV-2) with unusually minimal antibody-dependent enhancement (ADE). To selectively display the binding epitope of 3H5, we strategically modified DENV-2 EDIII by shielding other known epitopes with engineered N-glycosylation sites. The modifications resulted in a glycosylated EDIII antigen termed \"EDIII mutant N\". This antigen was successfully used to sift through a dengue-immune scFv-phage library to select for scFv antibodies that bind to or closely surround the 3H5 epitope. The selected scFv antibodies were expressed as full-length human antibodies and showed potent neutralization activity to DENV-2 with low or negligible ADE resembling 3H5. These findings not only demonstrate the capability of the N-glycosylated EDIII mutant N as a tool to drive an epitope-directed antibody selection campaign but also highlight its potential as a dengue immunogen. This glycosylated antigen shows promise in focusing the antibody response toward a potently neutralizing epitope while reducing the risk of antibody-dependent enhancement.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[⁶⁸Ga]Ga-Schizokinen, a Potential Radiotracer for Selective Bacterial Infection Imaging.","authors":"Asma Akter, George Firth, Afnan M F Darwesh, Margaret S Cooper, Hataichanok Chuljerm, Agostino Cilibrizzi, Philip J Blower, Robert C Hider, Oliver Lyons, Silke Schelenz, Varun Mehra, Vincenzo Abbate","doi":"10.1021/acsinfecdis.4c00067","DOIUrl":"10.1021/acsinfecdis.4c00067","url":null,"abstract":"<p><p>Gallium-68-labeled siderophores as radiotracers have gained interest for the development of <i>in situ</i> infection-specific imaging diagnostics. Here, we report radiolabeling, <i>in vitro</i> screening, and <i>in vivo</i> pharmacokinetics (PK) of gallium-68-labeled schizokinen ([⁶⁸Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity. Our <i>in vitro</i> studies demonstrated its hydrophilic characteristics, neutral pH stability, and short-term stability in human serum and toward transchelation. <i>In vitro</i> uptake of [⁶⁸Ga]Ga-SKN by <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, <i>Staphylococcus aureus</i>, and <i>S. epidermidis</i>, but no uptake by <i>Candida glabrata</i>, <i>C. albicans</i>, or <i>Aspergillus fumigatus</i>, demonstrated its specificity to bacterial species. Whole-body [⁶⁸Ga]Ga-SKN positron emission tomography (PET) combined with computerized tomography (CT) in healthy mice showed rapid renal excretion with no or minimal organ uptake. The subsequent <i>ex vivo</i> biodistribution resembled this fast PK with rapid renal excretion with minimal blood retention and no major organ uptake and showed some dissociation of the tracer in the urine after 60 min postinjection. These findings warrant further evaluation of [⁶⁸Ga]Ga-SKN as a bacteria-specific radiotracer for infection imaging.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the Intracellular Action of the Antimicrobial Peptide A11 via an In-Depth Analysis of Its Effect on the Global Proteome of <i>Acinetobacter baumannii</i>.","authors":"Thanit Thitirungreangchai, Sittiruk Roytrakul, Ratchaneewan Aunpad","doi":"10.1021/acsinfecdis.4c00160","DOIUrl":"10.1021/acsinfecdis.4c00160","url":null,"abstract":"<p><p>The potential antimicrobial activity and low propensity to induce the development of bacterial resistance have rendered antimicrobial peptides (AMPs) as novel and ideal candidate therapeutic agents for the treatment of infections caused by drug-resistant pathogenic bacteria. The targeting of bacterial membranes by AMPs has been typically considered their sole mode of action; however, increasing evidence supports the existence of multiple and complementary functions of AMPs that result in bacterial death. An in-depth characterization of their mechanism of action could facilitate further research and development of AMPs with higher potency. The current study employs biophysics and proteomics approaches to unveil the mechanisms underlying the antibacterial activity of A11, a potential candidate AMP, against <i>Acinetobacter baumannii</i>, a leading cause of hospital-acquired infections (HAIs) and consequently, a serious global threat. A11 peptide was found to induce membrane depolarization to a high extent, as revealed by flow cytometry and electron microscopy analyses. The prompt intracellular penetration of A11 peptide, observed using confocal microscopy, was found to occur concomitantly with a very low degree of membrane lysis, suggesting that its mode of action predominantly involves a nonlytic killing mechanism. Quantitative proteomics analysis employed for obtaining insights into the mechanisms underlying the antimicrobial activity of A11 peptide revealed that it disrupted energy metabolism, interfered with protein homeostasis, and inhibited fatty acid synthesis that is essential for cell membrane integrity; all these impacted the cellular functions of <i>A. baumannii</i>. A11 treatment also impacted signal transduction associated with the regulation of biofilm formation, hindered the stress response, and influenced DNA repair processes; these are all crucial survival mechanisms of <i>A. baumannii</i>. Additionally, robust antibacterial activity was exhibited by A11 peptide against multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical isolates of <i>A. baumannii</i>; moreover, A11 peptide exhibited synergy with levofloxacin and minocycline as well as low propensity for inducing resistance. Taken together, the findings emphasize the therapeutic potential of A11 peptide as an antibacterial agent against drug-resistant <i>A. baumannii</i> and underscore the need for further investigation.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Biological Evaluation of Cyanoacrylamides and 5-Iminopyrrol-2-Ones Against Naegleria fowleri","authors":"Javier Chao-Pellicer,&nbsp;Samuel Delgado-Hernández,&nbsp;Iñigo Arberas-Jiménez,&nbsp;Ines Sifaoui,&nbsp;David Tejedor*,&nbsp;Fernando García-Tellado,&nbsp;José E. Piñero* and Jacob Lorenzo-Morales*,&nbsp;","doi":"10.1021/acsinfecdis.4c0043910.1021/acsinfecdis.4c00439","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00439https://doi.org/10.1021/acsinfecdis.4c00439","url":null,"abstract":"<p >Primary amoebic meningoencephalitis is caused by the free-living amoeba <i>Naegleria fowleri</i>. The lack of standardized treatment has significantly contributed to the high fatality rates observed in reported cases. Therefore, this study aims to explore the anti-<i>Naegleria</i> activity of eight synthesized cyanoacrylamides and 5-iminopyrrol-2-ones. Notably, QOET-109, QOET-111, QOET-112, and QOET-114 exhibited a higher selectivity index against <i>Naegleria</i> compared to those of the rest of the compounds. Subsequently, these chemicals were assessed against the resistant stage of <i>N. fowleri</i>, demonstrating activity similar to that observed in the vegetative stage. Moreover, characteristic events of programmed cell death were evidenced, including chromatin condensation, increased plasma membrane permeability, mitochondrial damage, and heightened oxidative stress, among others. Finally, this research demonstrated the <i>in vitro</i> activity of the cyanoacrylamide and 5-iminopyrrol-2-one molecules, as well as the induction of metabolic event characteristics of regulated cell death in <i>Naegleria fowleri</i>.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142228408","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":"Identifying Rab2 Protein as a Key Interactor of Centrin1 Essential for Leishmania donovani Growth","authors":"Roshanara,&nbsp;Rati Tandon,&nbsp;Mirza Sarwar Baig,&nbsp;Sanchita Das,&nbsp;Rahul Srivastava,&nbsp;Niti Puri*,&nbsp;Hira L. Nakhasi* and Angamuthu Selvapandiyan*,&nbsp;","doi":"10.1021/acsinfecdis.4c0035110.1021/acsinfecdis.4c00351","DOIUrl":"https://doi.org/10.1021/acsinfecdis.4c00351https://doi.org/10.1021/acsinfecdis.4c00351","url":null,"abstract":"<p >Previously, we have demonstrated that deletion of a growth-regulating gene (<i>LdCen1</i>) in the <i>Leishmania donovani</i> parasite (<i>LdCen1</i>^{<i>–/–</i>}) attenuated the parasite’s intracellular amastigote growth but not the growth of extracellular promastigotes. <i>LdCen1</i>^{<i>–/–</i>} parasites were found to be safe and efficacious against homologous and heterologous <i>Leishmania</i> species as a vaccine candidate in animal models. The reason for the differential growth of <i>LdCen1</i>^{<i>–/–</i>} between the two stages of the parasite needed investigation. Here, we report that <i>LdCen1</i> interacts with a novel Ras-associated binding protein in <i>L. donovani</i> (LdRab2) to compensate for the growth of <i>LdCen1</i>^{<i>–/–</i>} promastigotes. LdRab2 was isolated by protein pull-down from the parasite lysate, followed by nano-LC–MS/MS identification. The RAB domain sequence and the functional binding partners of the LdRab2 protein were predicted via Search Tool for the Retrieval of Interacting Proteins (STRING) analysis. The closeness of the LdRab2 protein to other reported centrin-binding proteins with different functions in other organisms was analyzed via phylogenetic analysis. Furthermore, <i>in vitro</i> and <i>in silico</i> analyses revealed that LdRab2 also interacts with other <i>L. donovani</i> centrins 3–5. Since centrin is a calcium-binding protein, we further investigated calcium-based interactions and found that the binding of LdRab2 to LdCen1 and LdCen4 is calcium-independent, whereas the interactions with LdCen3 and LdCen5 are calcium-dependent. The colocalization of LdCen1 and LdRab2 at the cellular basal-body region by immunofluorescence supports their possible functional association. The elevated expression of the LdRab2 protein in the mutant promastigotes suggested a probable role in compensating for the promastigote growth of this mutant strain, probably in association with other parasite centrins.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142228341","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}