Pathogens最新文献

{"title":"Infection-Associated Flares in Systemic Lupus Erythematosus.","authors":"Giuseppe A Ramirez, Chiara Calabrese, Marta Secci, Luca Moroni, Gabriele D Gallina, Giovanni Benanti, Enrica P Bozzolo, Marco Matucci-Cerinic, Lorenzo Dagna","doi":"10.3390/pathogens13110934","DOIUrl":"10.3390/pathogens13110934","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is characterised by generalised immune dysfunction, including infection susceptibility. Infection-associated flares (IAFs) are common and might rapidly self-resolve, paralleling infection resolution, but their specific clinical phenotype is poorly understood. Therefore, we screened 2039 consecutive visits and identified 134 flares, defined as a loss of the lupus low disease activity state (LLDAS), from 1089 visits at risk spanning over multiple follow-up years, yielding an average yearly LLDAS deterioration rate of 17%. Thirty-eight IAFs were isolated from the total flares and were mostly related to bacterial and herpesvirus infections. When compared to other flares (OFs; n = 98), IAFs showed no milder patterns of organ involvement and similar rates of long-term damage accrual, as estimated by conventional clinimetrics. Arthritis in IAFs was more severe than that in OFs [median (interquartile range) DAS-28 2.6 (2.3-4.1) vs. 2.0 (1.6-2.7); <i>p</i> = 0.02]. Viral IAFs were characterised by atypically lower levels of anti-DNA antibodies (<i>p</i> < 0.001) and possibly abnormally high complement levels when compared to flares of different origin. These data suggest that IAFs are of comparable or even higher severity than OFs and may subtend distinct pathophysiological mechanisms that are poorly tackled by current treatments. Further research is needed to confirm these data.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"13 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11597141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of Bacteremia in Patients with Hematological Malignancies and Hematopoietic Stem Cell Transplantation and the Impact of Antibiotic Resistance on Mortality: Data from a Multicenter Study in Argentina.","authors":"Fabián Herrera, Diego Torres, Ana Laborde, Rosana Jordán, Lorena Berruezo, Inés Roccia Rossi, Noelia Mañez, Lucas Tula, María Laura Pereyra, Andrea Nenna, Patricia Costantini, José Benso, María Luz González Ibañez, María José Eusebio, Nadia Baldoni, Laura Alicia Barcán, Sandra Lambert, Martín Luck, Fernando Pasterán, Alejandra Corso, Melina Rapoport, Federico Nicola, María Cristina García Damiano, Renata Monge, Ruth Carbone, Mariana Reynaldi, Graciela Greco, Miriam Blanco, María Laura Chaves, Marcelo Bronzi, Alberto Carena","doi":"10.3390/pathogens13110933","DOIUrl":"10.3390/pathogens13110933","url":null,"abstract":"<p><p>The epidemiology of bacteremia and the antibiotic resistance profile (ARP) of Gram-negative bacilli (GNB) in hematological malignancies (HM) and hematopoietic stem cell transplant (HSCT) patients may differ according to geographic region. In addition, multidrug-resistant organisms (MDROs) may impact mortality. This is a prospective, observational, and multicenter study. The first episodes of bacteremia in adult patients with HM or HSCT were included. The risk factors for 30-day mortality were identified. One thousand two hundred and seventy-seven episodes were included (HM: 920; HSCT: 357). GNB were isolated in 60.3% of episodes, with Enterobacterales (46.9%) and <i>P. aeruginosa</i> (8.5%) being the most frequent. Gram-positive cocci were isolated in 41.9% of episodes, with coagulase-negative staphylococci (19.8%) and <i>S. aureus</i> (10.4%) being the most frequent. MDROs were isolated in 40.2% (24.4% GNB). The ARP of GNB in patients with HM vs. HSCT was cefepime: 36.8% vs. 45.7% (<i>p</i> = 0.026); piperacillin-tazobactam: 31.05% vs. 45.2% (<i>p</i> < 0.0001); carbapenems: 18.9% vs. 27.3% (<i>p</i> = 0.012); and aminoglycosides: 9.3% vs. 15.4% (<i>p</i> = 0.017), respectively. Overall mortality between patients with HM and HSCT was 17.5% vs. 17.6% (<i>p</i> = 0.951), respectively. The risk factors for mortality were relapsed and refractory underlying disease, corticosteroids use, respiratory source, septic shock, and GNB resistant to meropenem, while 7-day clinical response was a protective factor for survival. Bacteremia was frequently caused by GNB, with a large proportion of MDROs and a high level of antibiotic resistance, especially in patients with HSCT. Carbapenem-resistant GNB bacteremia was associated with a significant increase in mortality.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"13 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11597762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pseudorabies Virus Prevalence in Lung Samples of Hunted Wild Boars in Northwestern Greece.","authors":"Konstantinos Papageorgiou, Aikaterini Stoikou, Dimitrios K Papadopoulos, Efpraxia Tsapouri-Kanoula, Ioannis A Giantsis, Dimitrios Papadopoulos, Efthymia Stamelou, Marina Sofia, Charalambos Billinis, Chrysanthi Karapetsiou, Evanthia Petridou, Spyridon K Kritas","doi":"10.3390/pathogens13110929","DOIUrl":"10.3390/pathogens13110929","url":null,"abstract":"<p><p>Aujeszky's Disease, caused by the pseudorabies virus (PRV), is an acute, often fatal disease affecting mainly pigs and incidentally other animals. While eradicated in several countries, PRV persists in wild boar populations, posing a risk to domestic pigs. This study investigates PRV prevalence in wild boars in the region of Epirus, located in the northwest of Greece. During the 2021-2022 hunting season, 110 lung samples from hunted wild boars were collected and analyzed for PRV DNA and cytopathic effects in cell cultures. PRV DNA was detected in 19 samples (17.3%), 18 of which exhibiting cytopathic effects, allowing for virus titer determination. Notably, in one sample, PRV DNA was detected without a cytopathic effect. These findings underscore the continued presence of PRV in Greek wild boars, highlighting the need for ongoing monitoring to prevent transmission to domestic pigs and other animals.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"13 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11597329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Immunochromatographic Test Strip Using Lanthanide-Labeled Fluorescent Nanoparticles for the Serological Detection of <i>Toxoplasma gondii</i> in Dogs and Cats.","authors":"Manyu Zhang, Qi Liu, Ruifang Li, Wei Jiang, Hongjin Zhao, Wenwei Sheng, Luming Xia, Zengqiang Li, Qing Sun, Jingying Du, Lei Lei, Quan Wang","doi":"10.3390/pathogens13110931","DOIUrl":"10.3390/pathogens13110931","url":null,"abstract":"<p><p><i>Toxoplasma gondii</i> (<i>T. gondii</i>) is an important zoonotic pathogen which induces both acute and chronic toxoplasmosis. Timely diagnosis of <i>T. gondii</i> is crucial for effective disease management. Here, we present a pioneering approach using europium (III)-chelated nanoparticles (EuNPs) in a rapid lateral flow immunochromatographic test strip (ICTS) for detecting <i>T. gondii</i> antibodies in serum samples. By conjugating EuNPs with Staphylococcus aureus protein A, we efficiently captured <i>T. gondii</i>-specific antibodies, which bound to <i>T. gondii</i> antigens on the test line (T-line), generating a distinct fluorescent signal. Employing this novel method, we conducted an extensive epidemiological investigation of <i>T. gondii</i> infections among dogs and cats in Shanghai, China. This innovative ICTS allows for rapid results within 25 min, which include a qualitative result through naked-eye observation under an ultraviolet lamp and a quantitative one derived using a strip reader. With a detection limit of 1:6400 for dog positive serum and no cross-reactivity with other canine and feline pathogens, the EuNPs-ICTS demonstrated excellent consistency with standard enzyme-linked immunosorbent assay results for dogs (κ = 0.91) and cats (κ = 0.92). In addition, 20.38% of 996 dog serum samples and 14.18% of 416 cat serum samples revealed <i>T. gondii</i> antibodies, highlighting the efficacy of this approach. Our study presents a rapid, sensitive, specific, and reproducible EuNPs-ICTS, serving as a promising tool for on-the-spot diagnosis of <i>T. gondii</i> infections in dogs and cats.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"13 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11597420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fungi Associated with Olive Tree (cv. 'Nocellara del Belice') Decay in Trapani Province (Sicily, Italy).","authors":"Marika Lamendola, Giulia Mirabile, Josè Muratore, Livio Torta","doi":"10.3390/pathogens13110932","DOIUrl":"10.3390/pathogens13110932","url":null,"abstract":"<p><p>Recently, in several locations in the province of Trapani (Sicily, Italy), olive growers have reported cases of decaying olive trees of cv. 'Nocellara del Belice', showing symptoms of defoliation, branch drying, xylem browning, and reduced production. Internal symptoms include white and brown wood rot, starting from the base of the trunk. These alterations have been observed in trees irrigated using a pipe system at the trunk with spray sprinklers. To identify the causal agents of decay, some trees were eradicated and dissected, and woody samples were processed to isolate and identify the associated fungal micro-organisms. The most common colonies were identified using morphological (macro- and microscopical observation) and molecular (PCR amplification of the rDNA-ITS region) analyses. Nine fungal taxa were identified, of which four were associated with this decay syndrome (<i>Coriolopsis gallica</i>, <i>Fomitiporia mediterranea</i>, <i>Kirschsteiniothelia</i> sp., and <i>Pleurostoma richardsiae</i>), three were considered ubiquitous and opportunistic fungi (<i>Alternaria</i> spp., <i>Aspergillus amstelodami</i>, and <i>Trichoderma</i> sp.), and the other two were <i>mycelia sterilia</i>. Artificial inoculation satisfied Koch's postulates, confirming the pathogenicity of the aforementioned fungi, even though the infections in the fields seem to be related to the irrigation system. This hypothesis would seem to be confirmed by the progression of decay over time in the trees subjected to the irrigation system described but not reported in olive groves differently managed. It is therefore considered appropriate to conduct further and more in-depth investigations aimed at studying the correlation between the irrigation system, presence of fungal agents, and manifestation of the syndrome. A further ongoing investigation is aimed at the use of biostimulants (Agrusaver, Savory Sun, VA LLC) on symptomatic trees, with the aim of both improving the vegetative performance of the host and limiting the symptoms detected in the field.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"13 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11597174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Detection of <i>Chlamydia pneumoniae</i>, <i>Helicobacter pylori</i> and <i>Cytomegalovirus</i> in Non-Atherosclerotic Arteries of Patients with Coronary Artery Disease.","authors":"Dalila Šačić, Uroš Tomić, Jelena Milašin, Svetozar Putnik, Milena Jovanović, Sanja Radojević Škodrić, Sofija Glumac","doi":"10.3390/pathogens13110927","DOIUrl":"10.3390/pathogens13110927","url":null,"abstract":"<p><p>Atherosclerotic coronary artery disease (ACAD) is a major cause of global morbidity and mortality, characterized as an inflammatory process due to damage to blood vessel walls by risk factors like aging, hyperlipidemia, hypertension, smoking, and diabetes. Infectious agents, including <i>Chlamydia pneumoniae</i> (Cpn), Cytomegalovirus (CMV), and <i>Helicobacter pylori</i> (HP), have been implicated in ACAD's pathophysiology. A study with 56 subjects undergoing coronary artery bypass grafting (CABG) aimed to detect Cpn, CMV, and HP DNA in unaffected artery segments and explore associations with disease progression and inflammation markers. The study found infectious agents' DNA in 21.4% of samples, HP in eight samples, and CMV and Cpn in four samples each. Significant correlations were observed between HP and overweight or obese subjects, as well as between the presence of infectious agents and inflammation marker values. An association between HP and renal function was also noted. The findings reaffirm previous discoveries of infectious agents in non-clinically affected arteries used as CABG grafts. Correlations identified between the presence of HP, CMV, and Cpn DNA in grafts and several biomarkers of inflammation and obesity emphasize the potential role of these infectious agents in ACAD pathogenesis.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"13 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11597713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal Parasites and Hematological Parameters in Children Living in Ambatoboeny District, Madagascar.","authors":"Wanesa Richert, Daria Kołodziej, Danuta Zarudzka, Daniel Kasprowicz, Dariusz Świetlik, Krzysztof Korzeniewski","doi":"10.3390/pathogens13110930","DOIUrl":"10.3390/pathogens13110930","url":null,"abstract":"<p><p>Madagascar is one of the poorest countries in the world. The country's extreme weather conditions, poor sanitation, and weak economy facilitate the spread of parasitic diseases. Infections with intestinal parasites are particularly dangerous for children because they can cause malnutrition and anemia, which, in turn, have a negative effect on children's cognitive functions and physical development. The aim of the present study was to analyze the prevalence of intestinal parasites and to assess hematological parameters in a group of children living in northern Madagascar. The screening was conducted in May 2024 in the Clinique Medicale Beyzym in Manerinerina, the Ambatoboeny district. It involved a sample of 208 children aged 0-17 years. Single stool samples were collected from all study participants. The samples were fixed in SAF fixative and then transported from Africa to Europe for further diagnostics at the Department of Epidemiology and Tropical Medicine, the Military Institute of Medicine-the National Research Institute in Poland. First, the samples were analyzed by light microscopy methods using three different diagnostic techniques (direct smear, decantation with distilled water, and the Fülleborn method). Next, they were tested by molecular biology methods (real-time PCR). Blood samples for the assessment of hematological parameters were collected at the healthcare center in Madagascar. The prevalence of intestinal parasites in the study sample was 61.5%. Helminths were found in 15.2% of the investigated children, and <i>Giardia intestinalis</i> (20.5%) was found to be the most prevalent parasite in the study population. Most infections were caused by potentially pathogenic stramenopila <i>Blastocystis</i> spp. (32.0%). Mean Hb, HCT, MCV, MCH, and MCHC levels in the study participants were below normal values. However, no correlation was found between the presence of a parasitic infection and low hematological parameters, which are a clinical sign of anemia. High rates of infections with intestinal parasites in children living in northern Madagascar support the necessity to introduce long-term preventive measures, which would limit the spread of parasitic diseases in the Malagasy population. Low hematological parameters in non-infected children may be indicative of persistent malnutrition or infection with other parasites, e.g., malaria or schistosomiasis.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"13 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11597123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An In Silico Approach to Discover Efficient Natural Inhibitors to Tie Up Epstein-Barr Virus Infection.","authors":"Ayan Das, Mumtaza Mumu, Tanjilur Rahman, Md Abu Sayeed, Md Mazharul Islam, John I Alawneh, Mohammad Mahmudul Hassan","doi":"10.3390/pathogens13110928","DOIUrl":"10.3390/pathogens13110928","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a member of the herpes virus family. EBV is a widespread virus and causes infectious mononucleosis, which manifests with symptoms such as fever, fatigue, lymphadenopathy, splenomegaly, and hepatomegaly. Additionally, EBV is associated with different lymphocyte-associated non-malignant, premalignant, and malignant diseases. So far, no effective treatment or therapeutic drug is known for EBV-induced infections and diseases. This study investigated natural compounds that inhibit EBV glycoprotein L (gL) and block EBV fusion in host cells. We utilised computational approaches, including molecular docking, in silico ADMET analysis, and molecular dynamics simulation. We docked 628 natural compounds against gL and identified the four best compounds based on binding scores and pharmacokinetic properties. These four compounds, with PubChem CIDs 4835509 (CHx-HHPD-Ac), 2870247 (Cyh-GlcNAc), 21206004 (Hep-HHPD-Ac), and 51066638 (Und-GlcNAc), showed several interactions with EBV gL. However, molecular dynamics simulations indicated that the protein-ligand complexes of CID: 4835509 (CHx-HHPD-Ac) and CID: 2870247 (Cyh-GlcNAc) are more stable than those of the other two compounds. Therefore, CIDs 4835509 and 2870247 (Cyh-GlcNAc) may be potent natural inhibitors of EBV infection. These findings can open a new way for effective drug design against EBV and its associated infections and diseases.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"13 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11597430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting Treatment Outcomes in Patients with Drug-Resistant Tuberculosis and Human Immunodeficiency Virus Coinfection, Using Supervised Machine Learning Algorithm.","authors":"Mojisola Clara Hosu, Lindiwe Modest Faye, Teke Apalata","doi":"10.3390/pathogens13110923","DOIUrl":"10.3390/pathogens13110923","url":null,"abstract":"<p><p>Drug-resistant tuberculosis (DR-TB) and HIV coinfection present a conundrum to public health globally and the achievement of the global END TB strategy in 2035. A descriptive, retrospective review of medical records of patients, who were diagnosed with DR-TB and received treatment, was conducted. Student's <i>t</i>-test was performed to assess differences between two means and ANOVA between groups. The Chi-square test with or without trend or Fischer's exact test was used to test the degree of association of categorical variables. Logistic regression was used to determine predictors of DR-TB treatment outcomes. A decision tree classifier, which is a supervised machine learning algorithm, was also used. Python version 3.8. and R version 4.1.1 software were used for data analysis. A <i>p</i>-value of 0.05 with a 95% confidence interval (CI) was used to determine statistical significance. A total of 456 DR-TB patients were included in the study, with more male patients (n = 256, 56.1%) than female patients (n = 200, 43.9%). The overall treatment success rate was 61.4%. There was a significant decrease in the % of patients cured during the COVID-19 pandemic compared to the pre-pandemic period. Our findings showed that machine learning can be used to predict TB patients' treatment outcomes.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"13 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11597124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression by RNA Polymerase I Inhibitors Varies Greatly Between Distinct RNA Polymerase I Transcribed Genes in Malaria Parasites.","authors":"Hermela Samuel, Riward Campelo Morillo, Björn F C Kafsack","doi":"10.3390/pathogens13110924","DOIUrl":"10.3390/pathogens13110924","url":null,"abstract":"<p><p>The transcription of ribosomal RNA (rRNA) by RNA Polymerase I (Pol I) is the rate-limiting step in ribosome biogenesis and a major determinant of cellular growth rates. Unlike other eukaryotes, which express identical rRNA from large tandem arrays of dozens to hundreds of identical rRNA genes in every cell, the genome of the human malaria parasite <i>Plasmodium falciparum</i> contains only a handful single-copy 47S rRNA loci that differ substantially from one another in length, sequence, and expression in different cell types. We found that the growth of the malaria parasite was acutely sensitive to the Pol I inhibitors 9-hydroxyellipticine and BMH-21 and demonstrated that they greatly reduce the transcription of 47S rRNAs as well as the transcription of other non-coding RNA genes. This makes P. falciparum only the second known organism where RNA Polymerase I transcribes genes other than the 47S rRNAs. We found that the various types of Pol I-transcribed genes differed by more than two orders of magnitude in their susceptibility to these inhibitors and explored the implications of these findings for the regulation of rRNA in <i>P. falciparum</i>.</p>","PeriodicalId":19758,"journal":{"name":"Pathogens","volume":"13 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11597781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}