Cellular Microbiology最新文献

{"title":"Antitumor Effect of Apilactobacillus kosoi 10H by Inducing Immunostimulatory Macrophages","authors":"Fuka Takahashi,&nbsp;Tai-Ying Chiou,&nbsp;Minako Tsukamoto,&nbsp;Satsuki Moriyama,&nbsp;Tomoya Takahashi,&nbsp;Sachi Tanaka","doi":"10.1155/cmi/4115145","DOIUrl":"https://doi.org/10.1155/cmi/4115145","url":null,"abstract":"<p><i>Apilactobacillus kosoi</i> (<i>A. kosoi</i>) 10H is a fructophilic lactic acid bacterium found in vegetable sugar fermentation liquid. It has been shown to possess high intestinal immunostimulatory activity. In this study, we investigated the potential for <i>A. kosoi</i> 10H heat-killed cells and their components to convert the phenotype of immunosuppressive M2 macrophages to immunostimulatory M1 macrophages. We further investigated the ability of induction of apoptosis of cancer cell lines by macrophage culture medium in the presence of <i>A. kosoi</i> 10H heat-killed cells. After induction of macrophage differentiation by phorbol 12-myristate 13-acetate in a THP-1 human monocyte–derived cell line, immunosuppressive M2 macrophages were induced by interleukin-6 (IL-6). When <i>A. kosoi</i> 10H heat-killed cells were brought into contact with IL-6-induced M2 macrophages, the expression of CD163 and CD209, which are M2 macrophage markers, markedly decreased, and the expression of CD80, human leukocyte antigen-DR isotype (HLA-DR), and tumor necrosis factor-<i>α</i> (TNF-<i>α</i>), markers of M1 macrophages, markedly increased. A similar effect was observed with a water-soluble extract and a hydrophobic liquid extract from <i>A. kosoi</i> 10H heat-killed cells. In addition, when M2 macrophage culture medium that had been conditioned with <i>A. kosoi</i> 10H heat-killed cells was added to the MCF-7 breast cancer cell line, we found that apoptosis was induced. TNF-<i>α</i> in the medium conditioned with macrophages cultured in the presence of <i>A. kosoi</i> 10H heat-killed cells was found to be partially responsible for MCF-7 cell death. This study presents basic data on the potential to use lactic acid bacteria to improve the cancer microenvironment.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2025 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cmi/4115145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota Dysbiosis: A Neglected Risk Factor for Male and Female Fertility","authors":"Faeze Ahmadi Beni,&nbsp;Hossein Saffarfar,&nbsp;Anis Elhami,&nbsp;Mohammad Kazemi","doi":"10.1155/cmi/7808354","DOIUrl":"https://doi.org/10.1155/cmi/7808354","url":null,"abstract":"<p>Infertility is a condition where a male or female is unable to achieve pregnancy through at least 1 year of regular, unprotected sexual intercourse. There are several known causes and risk factors associated with infertility. The gut microbiota is a complex community of trillions of microorganisms living in the gut. Due to modern lifestyle changes, such as dietary habits, physical inactivity, and increasing antibiotic use, the diversity and composition of these microbes may change in a detrimental manner. Dysbiosis or an imbalance of the gut microbiota compared to a normal composition can lead to various abnormalities, such as obesity, Alzheimer’s, metabolic disorders, and infertility. This review will cover the factors influencing gut microbiota composition, the mechanisms by which gut microbiota contributes to infertility in men and women, the effects of gut microbiota on problems that may arise during pregnancy, and therapeutic methods for diseases caused by dysbiosis of the gut microbiota.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2024 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cmi/7808354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of the Plausible Drug Target via Network/Genome Analysis and Its Molecular Interaction Studies Against Multidrug Resistance Bacterial Pathogens","authors":"Sidra Abbas,&nbsp;Azra Yasmin,&nbsp;Shama Mujawar,&nbsp;Monaza Bibi,&nbsp;Abeer Kazmi,&nbsp;Saif Ur Rehman","doi":"10.1155/2024/6635476","DOIUrl":"https://doi.org/10.1155/2024/6635476","url":null,"abstract":"<p>Multidrug-resistant (MDR) pathogens such as <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, and <i>Enterobacter cloacae</i> have become a global health threat. Drug repositioning or repurposing has become a viable solution to combat the threat posed by MDR pathogens. A strategic approach to identifying potential new candidates as future molecular drug targets is presented in this study. Fifty proteins critical for virulence during systemic infection were selected from the entire genomes of MDR <i>E. coli</i> MB641 and <i>Enterobacter cloacae</i> MB649, which were isolated from infected orthopaedic implants. Interaction networks were built using the STRING database to visualise the positioning of the selected virulence proteins in the network space and support their suitability for therapeutic targeting. The two significant virulence proteins FliG and FlhA, which were discovered by network analysis, were suggested as prospective treatment targets. To test the stability of the protein–drug complexes, the preidentified proteins were docked with 10 marketed antibacterial drugs and six phytochemicals. Amikacin, rifampicin, streptomycin, and tetracycline had the best binding interaction and stability for both strains, according to our findings. Molecular dynamic simulation studies were performed for amikacin and catechin at 100 ns. Both hydrophobic and hydrophilic stable contacts were seen in the active sites of amikacin and catechin with new chemical structures. Structural and conformational analysis of the docked protein-ligand complex was done by RMSD which showed stability of the amikacin and catechin complexes, whereas RMSF showed conformational changes. Based on the results, we propose the phytochemical catechin as the best theoretical lead, which may be further experimentally studied for selective inhibition.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2024 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/6635476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic Concentrations Affect the Virulence of Klebsiella quasipneumoniae subsp. similipneumoniae Isolates","authors":"Berfin Eroğlu,&nbsp;Eda Delik,&nbsp;Burcu Emine Tefon-Öztürk","doi":"10.1155/2024/5920468","DOIUrl":"https://doi.org/10.1155/2024/5920468","url":null,"abstract":"<p><i>Klebsiella</i> species are becoming a major global public health concern. In particular, the increase in multidrug-resistant strains is a cause for concern. This study was aimed at determining the antibiotic susceptibility of two different isolates of <i>Klebsiella quasipneumoniae</i> subsp. <i>similipneumoniae</i> and determining the virulence characteristics and bacterial morphology under subminimum inhibitory concentrations (sub-MICs) of antibiotics. In this study, two multidrug-resistant <i>K. quasipneumoniae</i> subsp. <i>similipneumoniae</i> isolates were identified, one of which was clinical, and the other was isolated from freshwater. The MICs of the antibiotics meropenem, chloramphenicol, ciprofloxacin, and kanamycin were determined for these isolates. The effects of the sub-MICs on the virulence and morphological characteristics of the bacteria were investigated in comparison with <i>K. pneumoniae</i> (ATCC 13883). The MICs of meropenem, chloramphenicol, ciprofloxacin, and kanamycin were 0.04, 20, 2, and 8 <i>μ</i>g/mL in the clinical isolate; 0.2, 15, 5, and 2 <i>μ</i>g/mL in the freshwater isolate; and 0.03, 3, 0.1, and 0.3 <i>μ</i>g/mL for <i>K. pneumoniae</i>. The biofilm-forming ability of <i>K. quasipneumoniae</i> subsp. <i>similipneumoniae</i> isolates decreased with antibiotic sub-MICs. Siderophore activity increased only with MIC/4 of kanamycin and MIC/2 of chloramphenicol in the clinical isolate (<i>p</i> &gt; 0.05). Furthermore, bacterial morphology and expression of virulence genes were affected differently by the sub-MICs. This study showed that biofilm formation decreased and that the changes in bacterial morphology and expression of virulence genes were very different in the presence of 1/2 and 1/4 sub-MIC antibiotics.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2024 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/5920468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in the Gut Microbiota in Chinese Patients With Intrahepatic Cholestasis of Pregnancy","authors":"Xiaozhen Lei,&nbsp;Jiangyan Yu,&nbsp;Yan Huang,&nbsp;Hua Lai,&nbsp;Siming Xin,&nbsp;Xiaoming Zeng","doi":"10.1155/2024/1710924","DOIUrl":"https://doi.org/10.1155/2024/1710924","url":null,"abstract":"<p>Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease and the second most frequent cause of jaundice in pregnancy, but the etiology of it is poorly understood. By collecting blood and fecal samples from 12 healthy pregnant women (CON group) and 32 ICP patients (ICP group) in China, we performed 16s rRNA gene sequencing and analyzed microbial diversity. The results showed a decrease in species richness of the ICP group compared to that in the CON group, with a significant difference in species diversity between the two groups. Differential analysis revealed the following biomarkers: s__unclassified__Megamonas, g__Megamonas, f__Selenomonadaceae, c__Bacilli, and o__Lactobacillales. Importantly, we found a decrease in species richness of Selenomonadaceae at the family level and decreased bacilli at the class level in ICP patients. Correlation network analysis and functional gene prediction were performed accordingly. Our data provided new information linking microbiota and ICP, and are possibly helpful for further exploration of the disease.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2024 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/1710924","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Approaches to Suppressing Pseudomonas aeruginosa Growth and Virulence: Current Status and Future Directions","authors":"Sandip Patil,&nbsp;Xiaowen Chen,&nbsp;Feiqiu Wen","doi":"10.1155/2024/7938723","DOIUrl":"https://doi.org/10.1155/2024/7938723","url":null,"abstract":"<p><i>Pseudomonas aeruginosa</i>, an antibiotic-resistant opportunistic pathogen, poses significant challenges in treating infections, particularly in immunocompromised individuals. This review explores current and future innovative approaches to suppress its growth and virulence. We delve into the bacterium’s virulence factors, discussing existing strategies like antibiotics, bacteriophages, probiotics, and small-molecule inhibitors. Additionally, novel approaches, including RNA interference, CRISPR-Cas systems, and nanotechnology, show promise in preclinical studies. Despite advancements, challenges persist, prompting the need for a multifaceted approach targeting various aspects of <i>P. aeruginosa</i> pathogenesis for effective infection management. This review provides a comprehensive perspective on the status and future directions of innovative strategies against <i>P. aeruginosa.</i></p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2024 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/7938723","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indole May Help the Horizontal Transmission of Antibiotic Resistance Genes in E. coli Under Subinhibitory Concentrations of Cefotaxime Stress","authors":"Weiqi Dong,&nbsp;Panpan Du,&nbsp;Ruisen Huang,&nbsp;Shuoyan Lv,&nbsp;Hong Chen,&nbsp;Songlei Guan","doi":"10.1155/2024/9018205","DOIUrl":"https://doi.org/10.1155/2024/9018205","url":null,"abstract":"<p><b>Objectives:</b> Subinhibitory concentration of antibiotics in the environment is an important risk factor for the horizontal transmission of antibiotic resistance genes (ARGs). The signaling mechanism of resistance gene transmission remains unknown. The aim of this study was to investigate whether indole could be used as a molecular signal to help the spread of ARGs under the stress of subinhibitory concentrations of antibiotics.</p><p><b>Methods:</b> The effect of indole on conjugation frequency was investigated through a conjugation test, and its effect on the Type IV secretion system and pili gene expression of <i>E. coli</i> was observed. Meanwhile, we were investigating the trend of changes in indole regulatory factors i<i>bpA</i>, <i>tnaA</i>, and concentration pumps. Subsequently, we predicted the receptors that specifically bind to indole. Finally, our study focused on elucidating the regulatory mechanism of indole synthesis.</p><p><b>Results:</b> Conjugate frequency was significantly increased under 1/5MIC concentration cefotaxime stress. The transferred ARGs were <i>bla_CTX-M</i> and <i>foxA</i>. The mobile plasmid was IncY or IncI2. Meanwhile, the concentration of endogenous indole was also significantly increased. And, surprisingly, inhibition of endogenous indole production resulted in a significant decrease in conjugate frequency. However, the conjugate frequency increased once again when the strains reacquired the exogenous indole. Furthermore, the fluctuation trends of indole-regulated factor (<i>ibpA</i>, <i>tnaA</i>) mRNA and concentration pumps (<i>acrEF</i>, <i>mtr</i>) mRNA consistently with that of indole. Then, we found that the receptors of indole may be four targets of TCSs: CreC, PhoB, AtoC, and UhpA. More than that, when strains retrieved the exogenous indole again, the mRNA levels of T4SS (<i>virB2</i>, <i>virB6</i>, and <i>virD4</i>) and <i>pppA</i> (<i>coding Pili precursor</i>) genes significantly increased. This indicates that there is a close relationship between indole and conjugated channels, which are necessary for horizontal transfer of genetic material. And then, the trends of indole and <i>tnaA</i> mRNA were consistent with that of <i>ibpA</i> (one of SOS response). So, this result confirmed that indole was regulated by SOS response under subinhibitory concentrations of antibiotics.</p><p><b>Conclusions:</b> It is always known that subinhibitory concentrations of antibiotics stimulate an SOS response in <i>E. coli</i>, which helps in the horizontal spread of ARGs by modulating indole.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2024 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/9018205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing the Antibacterial Activity of the Drug Teniposide Against Gram-Positive Bacteria","authors":"Federica Dell’Annunziata,&nbsp;Veronica Folliero,&nbsp;Roberta Della Marca,&nbsp;Francesca Palma,&nbsp;Giuseppina Sanna,&nbsp;Anna De Filippis,&nbsp;Pasquale Pagliano,&nbsp;Aldo Manzin,&nbsp;Gianluigi Franci,&nbsp;Massimiliano Galdiero","doi":"10.1155/2024/9389729","DOIUrl":"https://doi.org/10.1155/2024/9389729","url":null,"abstract":"<p>Drug repurposing is sparking considerable interest due to reduced costs and development times. The current study details the screening of teniposide, an antitumor drug, for its antibacterial activity against both Gram-positive and Gram-negative strains, with a focus on <i>Staphylococcus epidermidis</i> (<i>S. epidermidis</i>), the primary causative agent of nosocomial and transplant-related infections. The cytotoxicity was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and hemolysis assays on immortalized human keratinocyte (HaCaT) cells and human erythrocytes. After 20 h of treatment, the recorded concentrations causing 50% cytotoxicity (CC₅₀) and hemolysis (HC₅₀) were 33.63 and 121.55 <i>μ</i>g/mL, respectively. The antibacterial screening employed disk diffusion, the broth microdilution method, LIVE/DEAD staining, and a time-killing test. The drug induced a growth inhibitory area in the 22–25 mm range for all Gram-positive strains. The minimum concentration that inhibited 90% of bacteria (MIC₉₀) was 6.25 <i>μ</i>g/mL against <i>Staphylococcus aureus</i> and <i>S. epidermidis</i> and 12.5 <i>μ</i>g/mL versus <i>Enterococcus faecalis</i>, exhibiting bactericidal action. Treatment resulted in <i>S. epidermidis</i> cell morphology deformities and damage to the cell membrane, observed by scanning electron microscopy (SEM). Mechanism analysis revealed alterations in the selective permeability of the cell membrane, observed under the fluorescence microscope by the absorption of propidium iodide (PI). The synergistic effect of teniposide in combination with fosfomycin and gentamicin was documented by disk diffusion and checkboard assay, recording a fractional inhibitory concentration index (FICI) of 0.28 and 0.37, respectively. The drug’s action on <i>S. epidermidis</i> biofilm biomass was investigated using crystal violet (CV) and MTT. Teniposide affected biofilm viability in a dose-dependent manner, inducing, at a concentration of 3.12 <i>μ</i>g/mL, a matrix inhibition of about 42% and 61%, with a sessile metabolic activity of 54% and 24% recorded after 2 and 24 h, respectively. Overall, this study suggests the potential repurposing of the anticancer drug teniposide as a therapeutic agent to counteract <i>S. epidermidis</i> infections.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2024 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/9389729","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Dimensional Culture Modelling Reveals Divergent Mycobacterium tuberculosis Virulence and Antimicrobial Treatment Response","authors":"Magdalena K. Bielecka,&nbsp;Liku B. Tezera,&nbsp;Elena Konstantinopoulou,&nbsp;Nicola Casali,&nbsp;Orestis L. Katsamenis,&nbsp;Ximena Gonzalo,&nbsp;Francis Drobniewski,&nbsp;Paul T. Elkington","doi":"10.1155/2024/6458900","DOIUrl":"10.1155/2024/6458900","url":null,"abstract":"<p>Tuberculosis (TB) remains a persistent epidemic, and the emergence of drug-resistant <i>Mycobacterium tuberculosis</i> (Mtb) presents a global healthcare threat. While some new agents have been successfully introduced, innovative technologies to evaluate emerging anti-TB compounds are required to inform transformative approaches. Mtb is an obligate human pathogen, and consequently utilizing models that are consistent with human disease is likely to be critical. We have developed a human 3-dimensional (3-D) cell culture model that reflects human disease gene expression patterns and causes Mtb to become pyrazinamide sensitive <i>in vitro</i>. Here, we identify key differences in virulence between the standard laboratory strain, Mtb H37Rv, and clinical isolates. We demonstrate that Mtb H37Rv is attenuated in the 3-D system, more susceptible to antibiotics and hyperinflammatory compared to clinical isolates. Prolonged <i>in vitro</i> culture of a clinical strain leads to attenuation. We then characterise antibiotic sensitivity of multi-drug-resistant Mtb within the 3-D model and define relative bactericidal activity. Finally, we demonstrate that verapamil increases efficacy of bedaquiline and delamanid antibiotic therapy. Taken together, our findings suggest that studying virulent clinical strains in an advanced cell culture system is a powerful adjunct to established methodologies to evaluate new interventions for TB.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2024 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140832320","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}

{"title":"Dual Control of Host Actin Polymerization by a Legionella Effector Pair","authors":"M. Pillon,&nbsp;C. Michard,&nbsp;N. Baïlo,&nbsp;J. Bougnon,&nbsp;K. Picq,&nbsp;O. Dubois,&nbsp;C. Andrea,&nbsp;L. Attaiech,&nbsp;V. Daubin,&nbsp;S. Jarraud,&nbsp;E. Kay,&nbsp;P. Doublet","doi":"10.1155/2024/8896219","DOIUrl":"10.1155/2024/8896219","url":null,"abstract":"<p>Host actin cytoskeleton is often targeted by pathogenic bacteria through the secretion of effectors. <i>Legionella pneumophila</i> virulence relies on the injection of the largest known arsenal of bacterial proteins, over 300 Dot/Icm type 4 secretion system effectors, into the host cytosol. Here, we define the functional interactions between VipA and LegK2, two effectors with antagonistic activities towards actin polymerization that have been proposed to interfere with the endosomal pathway. We confirmed the prominent role of LegK2 effector in <i>Legionella</i> infection, as the deletion of <i>legK2</i> results in defects in the inhibition of actin polymerization at the <i>Legionella</i>-containing vacuole, as well as in endosomal escape of bacteria and subsequent intracellular replication. More importantly, we observed the restoration of the <i>ΔlegK2</i> mutant defects, upon deletion of <i>vipA</i> gene, making LegK2/VipA a novel example of effector-effector suppression pair that targets the actin cytoskeleton and whose functional interaction impacts <i>L. pneumophila</i> virulence. We demonstrated that LegK2 and VipA do not modulate each other’s activity in a “metaeffector” relationship. Instead, the antagonistic activities of the LegK2/VipA effector pair would target different substrates, Arp2/3 for LegK2 and G-actin for VipA, to temporally control actin polymerization at the LCV and interfere with phagosome maturation and endosome recycling, thus contributing to the intracellular life cycle of the bacterium. Strikingly, the functional interaction between LegK2 and VipA is consolidated by an evolutionary history that has refined the best effector repertoire for the benefit of <i>L. pneumophila</i> virulence.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2024 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139578777","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}