{"title":"Genomic characterization of third-generation cephalosporin-resistant Escherichia coli strains isolated from diseased dogs and cats: Report from Japanese Veterinary Antimicrobial Resistance Monitoring","authors":"Yukari Hiraoka (Furuya), Hitoshi Abo, Mari Matsuda, Saki Harada, Mio Kumakawa, Takahiro Shirakawa, Manao Ozawa, Michiko Kawanishi, Hideto Sekiguchi, Yoko Shimazaki","doi":"10.1016/j.vetmic.2024.110220","DOIUrl":"10.1016/j.vetmic.2024.110220","url":null,"abstract":"<div><p>This study investigates the genomic characteristics of canine and feline cefotaxime (CTX, a third-generation cephalosporin)-resistant <em>Escherichia coli</em> using the JVARM, Japanese Veterinary Antimicrobial Resistance Monitoring System, a nationwide monitoring.</p><p>In this study, whole-genome sequencing (WGS) was performed on 51 canine and 45 feline CTX-resistant <em>E. coli</em> isolates, with certain isolates subjected to pulsed-field gel electrophoresis with S1 nuclease for plasmid–chromosome separation.</p><p>The most common <em>bla</em><sub>CTX-M</sub> genes were <em>bla</em><sub>CTX-M-27</sub> (dogs: 11/51 [21.6 %]; cat: 10/45 [22.2 %]), followed by <em>bla</em><sub>CTX-M-14</sub> (dogs: 10/51 [19.6 %]; cats: 10/45 [22.2 %]), and <em>bla</em><sub>CTX-M-15</sub> (dogs: 9/51 [17.6 %]; cats: 5/45 [11.1 %]). Besides β-lactamase genes, all isolates harbored <em>mdf</em>(A), a multidrug efflux pump, with resistance genes for aminoglycosides, sulfonamides, trimethoprims, macrolides and tetracyclines. None of the isolates had carbapenemase genes, such as <em>bla</em><sub>OXA-48</sub>, <em>bla</em><sub>NDM</sub>, and <em>bla</em><sub>IMP</sub>, whereas most of the isolates showed double mutations in <em>gyrA</em> and <em>parC</em>, which affected quinolone resistance. For the isolates separately analyzed for plasmid and chromosomal DNA via WGS, the majority of CTX-M genes were present on the plasmids. Some plasmids also harbored the same combination of resistance genes and plasmid replicon type, although they differed from isolates derived from different areas of Japan. The predominant plasmids were <em>bla</em><sub>CTX-M</sub>-<sub>27,</sub> <em>aadA5, aph(6)-Id, aph(3”)-Ib, sul1, sul2, tet</em>(A)<em>, dfrA17</em>, and <em>mph</em>(A) on IncF. The predominant combination of ST131, O25:H4, and B2 isolates comprised the largest cluster in the minimum spanning tree and the ST131 <em>E. coli</em> harboring <em>bla</em><sub>CTX-M-27</sub> from human in Japan was closely related to these isolates.</p><p>The results indicated that CTX-resistant canine and feline <em>E. coli</em> harbored multiple plasmids carrying the same combination of resistance genes and emphasizes the need to prevent the spread.</p></div><div><h3>Data Availability</h3><p>All raw short-read sequence data have been deposited in the DNA Data Bank of Japan. (DRR Run No, DRR335726–335821).</p></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"298 ","pages":"Article 110220"},"PeriodicalIF":2.4,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0378113524002426/pdfft?md5=caa688667aa8ce50c9fcc5b0b32cf762&pid=1-s2.0-S0378113524002426-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142088822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cong He , Rongjie Zhang , Liangyu Yang , Bin Xiang
{"title":"Andrographolide inhibits porcine epidemic diarrhea virus by inhibiting the JAK2-STAT3 pathway and promoting apoptosis","authors":"Cong He , Rongjie Zhang , Liangyu Yang , Bin Xiang","doi":"10.1016/j.vetmic.2024.110235","DOIUrl":"10.1016/j.vetmic.2024.110235","url":null,"abstract":"<div><p>Porcine epidemic diarrhea (PED) is an acute, virulent, and highly contagious disease caused by the porcine epidemic diarrhea virus (PEDV). The high mutation rate of PEDV makes it difficult to effectively control using traditional vaccines, emphasizing the need for novel anti-PEDV-specific drugs. Therefore, this study aimed to investigate the activity and mechanism of action of andrographolide (AND) against PEDV in <em>vitro</em> and in <em>vivo</em>. In <em>vitro</em> experiments showed that AND treatment significantly inhibited PEDV replication in a cell model. The mechanism is that AND treatment significantly suppressed PEDV-induced activation of the JAK2-STAT3 pathway, which promoted apoptosis and inhibited the proliferation of the virus. Moreover, PEDV-infected 3-day-old piglets were treated with AND, and clinical symptoms, intestinal morphology, and viral load were examined. In <em>vivo</em> experiments showed that AND treatment reduced clinical symptoms, ameliorated intestinal damage, and increased the survival rate of infected piglets by 16.7 %. Conclusively, this study contributes to the field of PEDV antiviral drug development and provides new directions for PED prevention and treatment.</p></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"298 ","pages":"Article 110235"},"PeriodicalIF":2.4,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multi-locus sequence typing and genetic diversity of antibiotic-resistant genes and virulence-associated genes in Burkholderia pseudomallei: Insights from whole genome sequencing of animal and environmental isolates in Thailand","authors":"Sa-ngob Laklaeng , Jirarat Songsri , Sueptrakool Wisessombat , Wanida Mala , Preeda Phothaworn , Wilaiwan Senghoi , Manit Nuinoon , Sithichoke Tangphatsornruang , Teumpong Wongtawan , Orachun Hayakijkosol , Anusak Kerdsin , Wiyada Kwanhian Klangbud","doi":"10.1016/j.vetmic.2024.110236","DOIUrl":"10.1016/j.vetmic.2024.110236","url":null,"abstract":"<div><p><em>Burkholderia pseudomallei</em> is a Gram-negative bacillus and the etiological agent of melioidosis in humans and animals. The disease is highly endemic in northern Australia and Southeast Asia. Comprehensive genomic data are essential for understanding the bacteria's dissemination and genetic relationships among strains from different geographical regions. In this study, we conducted antimicrobial susceptibility testing and whole-genome sequencing of 54 <em>B. pseudomallei</em> isolates obtained from environmental and animal sources in southern Thailand between 2011 and 2018. Their genomics were determined of antibiotic-resistant genes (ARGs), virulence-associated genes, mobile genetic elements (MGEs), sequence types (STs), and single nucleotide polymorphisms (SNPs) to evaluate their epidemiological relatedness. Remarkably, all 54 isolates displayed sensitivity to antimicrobial agents typically used for melioidosis treatment. We identified nine distinct sequence types: ST392, ST51, ST409, ST508, ST376, ST1721, ST389, ST395, and ST289. Oxacillinase genes and the resistance nodulation family of efflux pumps (RND) were identified as contributors to antimicrobial resistance. Phylogenetic analysis demonstrated close genetic relations with other strains isolated from Southeast Asia. Furthermore, 172 virulence-associated genes were identified among the isolates, suggesting variations in clinical presentations. These findings underscore the importance of ongoing molecular genetic surveillance of <em>B. pseudomallei</em> for effective healthcare management and reducing melioidosis mortality.</p></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"298 ","pages":"Article 110236"},"PeriodicalIF":2.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samy Kasem , Mi Htay Htay Yu , Noura Alkhalefa , Emad B. Ata , Mohamed Nayel , Walied Abdo , Ahmed S. Abdel-Moneim , Hideto Fukushi
{"title":"Impact of equine herpesvirus-1 ORF15 (EUL45) on viral replication and neurovirulence","authors":"Samy Kasem , Mi Htay Htay Yu , Noura Alkhalefa , Emad B. Ata , Mohamed Nayel , Walied Abdo , Ahmed S. Abdel-Moneim , Hideto Fukushi","doi":"10.1016/j.vetmic.2024.110234","DOIUrl":"10.1016/j.vetmic.2024.110234","url":null,"abstract":"<div><p>Equine herpesvirus 1 (EHV-1) causes respiratory illness, fetal loss, perinatal mortality, and myeloencephalopathy. This study investigated ORF15's impact on virus infectivity and neurovirulence. The Ab4p neurovirulent strain of EHV1 was used as a backbone to create Ab4p attB, Ab4p∆ORF15, and Ab4p∆ORF15R chimeras via BAC DNA transfection into RK-13 cells. Viral growth kinetics, plaque size, transcription, and growth were assessed in MDBK cells, mouse neurons, and fetal equine brain cells. Neurovirulence was evaluated post-intranasal inoculation into male CBA/N1 SPF mice, measuring signs, virus titers, and histopathological changes. Deletion of EUL45 (Ab4p-∆EUL45) reduced viral replication efficiency, resulting in decreased release and smaller plaques. EUL45 deletion also upregulated neighbouring genes (EUL46 and EUL44). Ab4p-∆EUL45 exhibited reduced virulence and poor growth in neural cells compared to wild-type viruses. This study sheds light on EUL45's role in EHV-1, viral replication, and regulation of EUL46 and EUL44 expression, suggesting potential as a vaccine candidate.</p></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"298 ","pages":"Article 110234"},"PeriodicalIF":2.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuqing Cao , Qingling Ren , Shuang Chang , Wenping Cui , Peng Zhao , Yixin Wang
{"title":"N6-methyladenosine RNA methylation modification regulates the transcription of viral-derived E (XSR) miRNAs to promote ALV-J replication","authors":"Yuqing Cao , Qingling Ren , Shuang Chang , Wenping Cui , Peng Zhao , Yixin Wang","doi":"10.1016/j.vetmic.2024.110218","DOIUrl":"10.1016/j.vetmic.2024.110218","url":null,"abstract":"<div><p>The E (XSR) element located in the 3′UTR of the ALV-J genome has the capability to transcribe and generate viral-derived E (XSR) miRNA. However, the biological function and transcriptional regulation mechanism of this process remain unclear. In this study, the impact of E (XSR) miRNA on ALV-J replication and the regulatory effect of N6-methyladenosine (m<sup>6</sup>A) methylation on its transcription were investigated. The results demonstrated that E (XSR) miRNA could stimulate ALV-J replication and suppress apoptosis in DF-1 cells <em>in vitro</em>. E (XSR) miRNA's promotion of ALV-J replication was not associated with the type I interferon pathway, but achieved by suppressing the expression of the host GPC5 gene. The transcription of E (XSR) miRNA could be promoted by m<sup>6</sup>A methylation modification, where m<sup>6</sup>A modification was found at the A6880 and A7016 sites of ALV-J gRNA. This study provides a new perspective on the transcription of ALV-J E (XSR) miRNA and its regulatory function in ALV-J replication.</p></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"298 ","pages":"Article 110218"},"PeriodicalIF":2.4,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hui Jiang , Mengle Jia , Jiaqi Xiong , Changrun Zhao , Ting Wang , Lingbao Kong , Qi Peng
{"title":"The network interactions between the porcine deltacoronavirus nucleocapsid protein and host cellular proteins","authors":"Hui Jiang , Mengle Jia , Jiaqi Xiong , Changrun Zhao , Ting Wang , Lingbao Kong , Qi Peng","doi":"10.1016/j.vetmic.2024.110225","DOIUrl":"10.1016/j.vetmic.2024.110225","url":null,"abstract":"<div><p>Porcine deltacoronavirus (PDCoV) is an emerging swine coronavirus that can cause diarrhea in pigs of all ages with varying severity. Host–virus protein interactions are critical for intracellular viral replication. Elucidating the interactions between cellular and viral proteins can help us to design antiviral strategies. PDCoV N protein is the most abundant and vital regulator in virus replication. In this study, 604 host proteins were identified to interact with PDCoV N protein by Co-IP combined with LC-MS, of which 243 proteins were specifically bound to N protein. PPI analysis revealed that the N-interacting host proteins are categorized into three groups: ribonucleoprotein complex biogenesis modulation, cellular nitrogen compound metabolism, and nucleic acid binding. GO and KEGG analyses showed that the host proteins are primarily involved in mRNA splicing, stress granule assembly, spliceosomal snRNP assembly. Additionally, four host proteins-TRIM25, HNRNPUL1, RPS27A, and SLC3A2-were selected to validate the interactome data through Co-IP and Confocal assays. This study can help in designing anti-PDCoV strategies and understanding the replication mechanism of PDCoV.</p></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"298 ","pages":"Article 110225"},"PeriodicalIF":2.4,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaomei Yue, Mariana Kikuti, Claudio Marcello Melini, Emily Geary, Paulo Fioravante, Cesar Agustin Corzo
{"title":"Enhancing disease surveillance and preparedness: An early warning tool for disease occurrence in U.S. swine breeding herds","authors":"Xiaomei Yue, Mariana Kikuti, Claudio Marcello Melini, Emily Geary, Paulo Fioravante, Cesar Agustin Corzo","doi":"10.1016/j.vetmic.2024.110215","DOIUrl":"10.1016/j.vetmic.2024.110215","url":null,"abstract":"<div><p>Understanding regional disease risk is critical for swine disease prevention and control. Since 2011, the Morrison Swine Health Monitoring Project (MSHMP) has strengthened partnerships among practitioners and producers to report health events (e.g., porcine reproductive and respiratory syndrome (PRRS) virus outbreaks) at the U.S. national level. Using MSHMP data and PRRS as an example, an early regional occurrence warning tool to provide near-real-time alerts was developed. MSHMP-participating production systems were invited to enroll. An algorithm was developed to calculate the number of PRRSV-positive sites near each enrolled site, determined from site-specific radius. The radius was determined in three steps. First, an initial radius of 25 miles was set for sites in pig-dense states and 50 miles for others. Secondly, four variables were generated to account for the sites within the initial radius: A) Total number of PRRSV-positive sites; B) Number of PRRSV-positive sites from other production systems; C) Total number of sites enrolled, and D) Total number of sites monitored by MSHMP. Subsequently, the reporting radius was automatically increased when confidentiality concerns arose. Results were compiled into system-specific reports and shared weekly with each participant. Reports have been shared since May 9, 2023, representing 178 breeding sites, comprising approximately 565 K sows. Examples of how participants use these reports include adjusting biosecurity programs, frequency of supply introduction, and transportation routes. The early occurrence warning tool developed in this study enhances producers' ability to communicate effectively and respond quickly to health threats, mitigating regional disease while preparing for foreign disease introductions.</p></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"298 ","pages":"Article 110215"},"PeriodicalIF":2.4,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0378113524002372/pdfft?md5=d62b4c47e3edd287e233099d3541315b&pid=1-s2.0-S0378113524002372-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Monitoring of pathogenic Leptospira infection in wolves (Canis lupus) from Spain and Italy","authors":"Moisés Gonzálvez , David Cano-Terriza , Manena Fayos , Barbara Moroni , Remigio Martínez , Serena Robetto , Álvaro Oleaga , Susana Remesar , Riccardo Orusa , Clara Muñoz-Hernández , Roser Velarde , Ignacio García-Bocanegra","doi":"10.1016/j.vetmic.2024.110222","DOIUrl":"10.1016/j.vetmic.2024.110222","url":null,"abstract":"<div><p>Leptospirosis is a bacterial disease of worldwide distribution with relevant implications for animal and human health. Different large wild carnivore species can act as reservoirs of this zoonotic pathogen. This study aimed to evaluate the circulation of <em>Leptospira</em> spp. in free-ranging wolves (<em>Canis lupus</em>) from southern Europe. A total of 281 kidney samples of wolves from Spain and Italy were collected between 2017 and 2023. The presence of <em>Leptospira</em> DNA was analysed by real-time PCR and phylogenetic analyses were carried out using a Bayesian approach. The overall prevalence was 3.2 % (9/281; 95 %CI: 1.1–5.3). <em>Leptospira</em> DNA was detected in nine of the 180 wolves from Spain (5.0 %; 95 %CI: 1.8–8.2), but not in the Italian wolf population (0 %; 0/101). Molecular analyses revealed high homology between the sequences obtained in the present study and isolates of <em>Leptospira interrogans</em> and <em>Leptospira borgpetersenii</em> from different rodent and domestic ungulate species. Our results provide evidence of a low and spatially heterogeneous circulation of this pathogen in wolf populations of southern Europe. The detection of zoonotic <em>Leptospira</em> species in this survey supports the need to consider wolf populations in monitoring programs for leptospirosis with a One Health approach.</p></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"298 ","pages":"Article 110222"},"PeriodicalIF":2.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S037811352400244X/pdfft?md5=7e8711540f2134a61360c2e9775b36e2&pid=1-s2.0-S037811352400244X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Wang , Xiu-Zhong Zhang , Xin-Yue Sun, Wen-Jun Tian, Xiao-Jia Wang
{"title":"Cellular RNA-binding proteins LARP4 and PABPC1 synergistically facilitate viral translation of coronavirus PEDV","authors":"Jing Wang , Xiu-Zhong Zhang , Xin-Yue Sun, Wen-Jun Tian, Xiao-Jia Wang","doi":"10.1016/j.vetmic.2024.110219","DOIUrl":"10.1016/j.vetmic.2024.110219","url":null,"abstract":"<div><p>Coronaviruses are causing epizootic diseases and thus are a substantial threat for both domestic and wild animals. These viruses depend on the host translation machinery to complete their life cycle. The current paper identified cellular RNA-binding proteins (RBPs), La-related protein 4 (LARP4) and polyadenylate-binding protein cytoplasmic 1 (PABPC1), as critical regulators of efficient translation of the coronavirus porcine epidemic diarrhea virus (PEDV) mRNA. In Vero cells, PEDV infection caused LARP4 to migrate from the nucleus to the cytoplasm in a chromosome region maintenance1 (CRM1)-independent pathway. In the absence of the nuclear export signal of LARP4, viral translation was not promoted by LARP4. A further study unveiled that the cytoplasmic LARP4 binds to the 3′-terminal untranslated region (3′UTR) of PEDV mRNA with the assistance of PABPC1 to facilitate viral translation. LARP4 knockdown reduced the promotion of the PABPC1-induced 3′UTR translation activity. Moreover, the rabbit reticulocyte lysate (RRL) system revealed that the prokaryotic expressed protein LARP4 and PABPC1 enhance PEDV mRNA translation. To our knowledge, this is the first study demonstrating that PEDV induces nucleo-cytoplasmic shuttling of LARP4 to enhance its own replication, which broadens our insights into how viruses use host's RBPs for the efficient translation of viral mRNA.</p></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"298 ","pages":"Article 110219"},"PeriodicalIF":2.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hai Hu , Guangdong Zhang , Mingxing Tian , Yi Yin , Yanqing Bao , Xiang Guan , Chan Ding , Shengqing Yu
{"title":"Brucella rough RB51 infection activates P53-Slc7a11-Gpx4/GSH pathway to induce ferroptosis to attenuate the intracellular survival on macrophages","authors":"Hai Hu , Guangdong Zhang , Mingxing Tian , Yi Yin , Yanqing Bao , Xiang Guan , Chan Ding , Shengqing Yu","doi":"10.1016/j.vetmic.2024.110224","DOIUrl":"10.1016/j.vetmic.2024.110224","url":null,"abstract":"<div><p><em>B. abortus</em> is a facultative intracellular bacterium that replicates within macrophages. Intracellular survival is one of the important indexes to evaluate the virulence of <em>Brucella</em>. Ferroptosis is a type of programmed cell death induced by the accumulation of free iron, reactive oxygen species (ROS), and toxic lipid peroxides, play roles on cancers, cardiovascular diseases, and inflammatory diseases. In this study, we found that <em>Brucella</em> rough strain RB51 induced ferroptosis on macrophages with reduced levels of host glutathione and glutathione peroxidase 4 (Gpx4), together with increased ferrous iron, lipid peroxidation, and ROS. The inhibitor ferrostatin-1 significantly reduced the ferroptosis of RB51-infected macrophages, confirming that ferroptosis occurred during infection with <em>Brucella</em> RB51. Furthermore, we found that RB51 infection induced ferroptosis is regulated by P53-Slc7a11-Gpx4/GSH signal pathway. Inhibiting P53 decreased the levels of ROS and lipid peroxidation, while the levels of Slc7a11, Gpx4 and GSH were rescued. More importantly, inhibiting ferroptosis by different ferroptosis inhibitors increased the intracellular survival of <em>Brucella</em> RB51, indicating ferroptosis functions on the attenuation of <em>Brucella</em> intracellular survival. Collectively, our observations demonstrate that <em>Brucella</em> RB51 infection induces ferroptosis on macrophages, which is regulated by P53-Slc7a11-Gpx4/GSH signal pathway and functions on the attenuation of intracellular survival of <em>Brucella</em>.</p></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"298 ","pages":"Article 110224"},"PeriodicalIF":2.4,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}