Cellular Microbiology最新文献

{"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}

{"title":"Molecular Docking, Dynamics Simulations, ADMET, and DFT Calculations: Combined In Silico Approach to Screen Natural Inhibitors of 3CL and PL Proteases of SARS-CoV-2","authors":"Sugumar Mohanasundaram,&nbsp;Porkodi Karthikeyan,&nbsp;Venkatesan Sampath,&nbsp;M. Anbazhagan,&nbsp;Sundramurthy Venkatesa Prabhu,&nbsp;Jamal M. Khaled,&nbsp;Muthu Thiruvengadam","doi":"10.1155/2024/6647757","DOIUrl":"10.1155/2024/6647757","url":null,"abstract":"<p>Considering natural compounds for the antiviral effect is another opportunity for exploring novel drug candidates for severe acute respiratory syndrome coronavirus 2. The selected natural compounds were interacted using a molecular docking approach. The 3D structures of the main protease and papain-like protease were used for the virtual screening to detect the potent inhibitor against SARS-CoV-2. The top-scored compounds were further analyzed for absorption, digestion, metabolism, excretion, and toxicity properties and density functional theory analysis. Our results indicated that glycyrrhizin exhibited better docking scores of -9.5 kcal/mol with main protease and -9.7 kcal/mol with papain-like protease. Next to glycyrrhizin, rutin showed a better docking score of -9.1 kcal/mol and -9.2 kcal/mol with 3-chymotrypsin-like and papain-like proteases. Violaxanthin and naringin occupied the subsequent position in the docking score table with 3CL and PL proteases, respectively. In addition, the crucial properties like drug likeliness and pharmacokinetics of the compounds were determined. There is no significant toxicity identified.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139476357","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":"Differences in Rhizosphere Microbial Community Structure and Composition in Resistance and Susceptible Wheat to Fusarium Head Blight","authors":"Han Li, Mingshuang Tang, Tao Zheng, Ming Yang, Youning Wang, Yating Shuai, Yan Li, Yibo Zhang, Dongfang Ma","doi":"10.1155/2023/9963635","DOIUrl":"https://doi.org/10.1155/2023/9963635","url":null,"abstract":"Fusarium head blight (FHB) is a serious disease of wheat that threatens wheat production worldwide. In this study, high-throughput sequencing technology was used to analyze the rhizosphere soil microbial metagenomes of 4 wheat cultivars with different levels of resistance to FHB. The results showed that there were differences in the diversity, structure, and composition of rhizosphere microorganisms between resistant and sensitive varieties. The rhizosphere soil bacterial diversity of the resistant wheat varieties Su Mai 3 and Yang Mai 16 was higher than that of the susceptible wheat varieties Zheng Mai 9023 and Zhou Mai 20. The diversity of rhizosphere fungi in resistant varieties was lower than that in susceptible varieties, but the abundance was higher than that in susceptible varieties. Variety was found to alter the community structure of wheat rhizosphere microorganisms. Resistant varieties SM3 and YM16 and moderately susceptible variety ZM9023 had similar microbial community structure, while highly susceptible variety ZM20 was significantly different from other varieties. The study is aimed at analyzing the effects of wheat varieties of different resistance to FHB on the composition and abundance of rhizosphere soil microbial community to screen out bacteria or fungi that can be used to control FHB, providing the theoretical basis for FHB biological control.","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135869727","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":"Commonality of Virulence-Promoting Function in Rhodococcus equi Virulence Associated Proteins (Vaps)","authors":"Timothy R. Ganderton, Daniel Ghete, Karen Hogg, Graeme J. Park, Christoph G. Baumann, Anthony J. Wilkinson, Paul R. Pryor","doi":"10.1155/2023/9141112","DOIUrl":"https://doi.org/10.1155/2023/9141112","url":null,"abstract":"Rhodococcus equi is a Gram-positive facultative intracellular pathogen associated with life-threatening bronchopneumonial disease in foals. Key to R. equi’s intracellular survival in host macrophages is the production of virulence associated proteins (Vaps). Numerous vap genes are found on virulence plasmids isolated from different species, and the Vaps share a high degree of sequence identity. VapA has been extensively studied, and although vapK and vapN genes from other R. equi virulence plasmids have been shown to be essential for R. equi intracellular survival, their mode of action is less characterised. We, therefore, examined whether VapK and VapN worked mechanistically in the same way as VapA. Indeed, like VapA, VapK and VapN neutralised lysosomal pH and reduced lysosomal hydrolase activity. A loss of VapA and R. equi virulence could be regained by the presence of either VapK or VapN. The acid-neutralisation activity was also observed to a lesser extent with VapB. There was a differential activity across these virulence-promoting Vaps with the most “acid-neutralising” activity found with VapN, then VapA and K, and finally VapB. These data suggest that VapA production, which is often found in equine infections, can be substituted by VapK and B (produced by plasmids often found in porcine species) or VapN (produced by plasmids often isolated in bovine and human samples). These data imply that the molecular mechanism(s) that VapA uses to neutralise lysosomal acidity should also be seen in VapN and K which will help guide researchers in identifying their precise mode of action and aid the future development of targeted therapeutics.","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136294886","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":"Analysis of Specific Allergens in the Serum of Patients with Allergic Diseases in the Shanxi Region of China","authors":"Jing Wu, Yuee Liu, M. Xie, Yanzhi Cui, Yaona Wei, Yan Cheng, Jing Yang, Hongxia Zhang, Lei Wang","doi":"10.1155/2023/1460961","DOIUrl":"https://doi.org/10.1155/2023/1460961","url":null,"abstract":"The aim of this study is to analyze the distribution characteristics of specific allergens based on the immunoglobulin E (IgE) test, performed using the sera of patients with allergic diseases in the Shanxi region of China. Sera from 3141 patients with allergic diseases were analyzed with immunoblotting for IgE antibodies specific to inhaled and ingested allergens. The distribution of allergens and association with factors such as disease profile, sex, age, and cosensitization of the patients who tested positive were analyzed. The most common positive rate of IgE specific to inhaled allergens was mugwort, followed by dust mite mix and common ragweed. The most common positive rate of IgE specific to ingested allergens was crab, followed by egg white and sea fish mix. When analyzed according to disease profile, mugwort was the most common allergen in asthma, rhinitis, and asthma combined with rhinitis. When analyzed by season, the allergens with the highest positive rates included tree mix (willow/poplar/elm), common ragweed, mugwort, and hop pollen from July through September. When analyzed by age, the allergens with the highest positive rates were tree mix, common ragweed, hop, house dust, cow’s milk, mutton/lamb, and peanut in participants aged 0–18 years and egg white in those aged ≥60 years. The radar charts showed cosensitization to multiple allergens. In the Shanxi region, the primary inhaled allergens were mugwort, dust mite mix (1: house dust mite/dust mite), and common ragweed. The primary ingested allergens were crab, egg white, and sea fish mix. There were differences in the positive rates of the allergens between genders, age groups, and seasons, and multiple allergens can cosensitize patients.","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45479341","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":"Ferroptosis Is a Potential Therapeutic Target for Pulmonary Infectious Diseases","authors":"Yurong Zhang, Dianlun Qian, Xiangfeng Bai, Shibo Sun","doi":"10.1155/2023/3875897","DOIUrl":"https://doi.org/10.1155/2023/3875897","url":null,"abstract":"Ferroptosis is a new type of iron-dependent cell death caused by lipid peroxide (LPO) accumulation and involved in disease of pulmonary infection. The dysregulation of iron metabolism, the accumulation of LPO, and the inactivation and consumption of glutathione peroxidase 4 (GPX4) are the crucial cause of ferroptosis. Pulmonary infectious diseases caused by Pseudomonas aeruginosa (PA), Mycobacterium tuberculosis (MTB), and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are associated with ferroptosis. Ferroptosis may be a potential therapeutic target for pulmonary infectious diseases. However, the mechanisms by which these infections are involved in ferroptosis and whether pulmonary infectious diseases caused by Staphylococcus aureus, Klebsiella pneumoniae, and Leishmania spp are related to ferroptosis are unclear. Accordingly, more researches are needed.","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44373940","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":"G1 Cell Cycle Arrest Is Induced by the Fourth Extracellular Loop of Meningococcal PorA in Epithelial and Endothelial Cells","authors":"M. Vassey, Rininta Firdaus, A. Aslam, L. Wheldon, N. Oldfield, D. Ala'aldeen, K. Wooldridge","doi":"10.1155/2023/7480033","DOIUrl":"https://doi.org/10.1155/2023/7480033","url":null,"abstract":"Neisseria meningitidis is the most frequent cause of bacterial meningitis and is one of the few bacterial pathogens that can breach the blood-brain barrier (BBB). The 37/67 kDa laminin receptor (LamR) was previously identified as a receptor mediating meningococcal binding to rodent and human brain microvascular endothelial cells, which form part of the BBB. The meningococcal surface proteins PorA and PilQ were identified as ligands for this receptor. Subsequently, the fourth extracellular loop of PorA (PorA-Loop4) was identified as the LamR-binding moiety. Here, we show that PorA-Loop4 targets the 37 kDa laminin receptor precursor (37LRP) on the cell surface by demonstrating that deletion of this loop abrogates the recruitment of 37LRP under meningococcal colonies. Using a circularized peptide corresponding to PorA-Loop4, as well as defined meningococcal mutants, we demonstrate that host cell interaction with PorA-Loop4 results in perturbation of p-CDK4 and Cyclin D1. These changes in cell cycle control proteins are coincident with cellular responses including inhibition of cell migration and a G1 cell cycle arrest. Modulation of the cell cycle of host cells is likely to contribute to the pathogenesis of meningococcal disease.","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47272920","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}