Virulence最新文献

{"title":"Characterization of Conserved Evolution in H7N9 Avian Influenza Virus Prior Mass Vaccination.","authors":"Dongchang He, Xiyue Wang, Huiguang Wu, Kairui Cai, Xiaoli Song, Xiaoquan Wang, Jiao Hu, Shunlin Hu, Xiaowen Liu, Chan Ding, Daxin Peng, Shuo Su, Min Gu, Xiufan Liu","doi":"10.1080/21505594.2024.2395837","DOIUrl":"https://doi.org/10.1080/21505594.2024.2395837","url":null,"abstract":"<p><p>Vaccination is crucial for the prevention and mitigation of avian influenza infections in China. The inactivated H7N9 vaccine, when administered to poultry, significantly lowers the risk of infection among both poultry and humans, while also markedly decreasing the prevalence of H7N9 detections. Highly pathogenic (HP) H7N9 viruses occasionally appear, whereas their low pathogenicity (LP) counterparts have been scarcely detected since 2018. However, these contributing factors remain poorly understood. We conducted an exploratory investigation of the mechanics via the application of comprehensive bioinformatic approaches. We delineated the Yangtze River Delta (YRD) H7N9 lineage into 5 clades (YRD-A to E). Our findings highlight the emergence and peak occurrence of the LP H7N9-containing YRD-E clade during the 5th epidemic wave in China's primary poultry farming areas. A more effective control of LP H7N9 through vaccination was observed compared to that of its HP H7N9 counterpart. YRD-E exhibited a tardy evolutionary trajectory, denoted by the conservation of its genetic and antigenic variation. Our analysis of YRD-E revealed only minimal amino acid substitutions along its phylogenetic tree and a few selective sweep mutations since 2016. In terms of epidemic fitness, the YRD-E was measured to be lower than that of the HP variants. Collectively, these findings underscore the conserved evolutionary patterns distinguishing the YRD-E. Given the conservation presented in its evolutionary patterns, the YRD-E LP H7N9 is hypothesized to be associated with a reduction following the mass vaccination in a relatively short period owing to its lower probability of antigenic variation that might affect vaccine efficiency.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porcine reproductive and respiratory syndrome virus infects the reproductive system of male piglets and impairs development of the blood-testis barrier.","authors":"Bingzhou Huang, Fengqin Li, Dong You, Lishuang Deng, Tong Xu, Siyuan Lai, Yanru Ai, Jianbo Huang, Yuancheng Zhou, Liangpeng Ge, Xiu Zeng, Zhiwen Xu, Ling Zhu","doi":"10.1080/21505594.2024.2384564","DOIUrl":"10.1080/21505594.2024.2384564","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease that threatens the global swine industry. Recent studies have focused on the damage that PRRSV causes to the reproductive system of male pigs, although pathological research is lacking. Therefore, we examined the pathogenic mechanisms in male piglets infected with PRRSV. Gross and histopathological changes indicated that PRRSV affected the entire reproductive system, as confirmed via immunohistochemical analysis. PRRSV infected Sertoli cells and spermatogonia. To test the new hypothesis that PRRSV infection in piglets impairs blood - testis barrier (BTB) development, we investigated the pathology of PRRSV damage in the BTB. PRRSV infection significantly decreased the quantity and proliferative capacity of Sertoli cells constituting the BTB. Zonula occludens-1 and β-catenin were downregulated in cell - cell junctions. Transcriptome analysis revealed that several crucial genes and signalling pathways involved in the growth and development of Leydig cells, Sertoli cells, and tight junctions in the testes were downregulated. Apoptosis, necroptosis, inflammatory, and oxidative stress-related pathways were activated, whereas hormone secretion-related pathways were inhibited. Many Sertoli cells and spermatogonia underwent apoptosis during early differentiation. Infected piglets exhibited disrupted androgen secretion, leading to significantly reduced testosterone and anti-Müllerian hormone levels. A cytokine storm occurred, notably upregulating cytokines such as tumour necrosis factor-α and interleukin-6. Markers of oxidative-stress damage (i.e. H₂O₂, malondialdehyde, and glutathione) were upregulated, whereas antioxidant-enzyme activities (i.e. superoxide dismutase, total antioxidant capacity, and catalase) were downregulated. Our results demonstrated that PRRSV infected multiple organs in the male reproductive system, which impaired growth in the BTB.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Pathogenesis and virulence of coronavirus disease: Comparative pathology of animal models for COVID-19.","authors":"Natalie M Kirk, Yuying Liang, Hinh Ly","doi":"10.1080/21505594.2024.2316438","DOIUrl":"10.1080/21505594.2024.2316438","url":null,"abstract":"<p><p>Animal models that can replicate clinical and pathologic features of severe human coronavirus infections have been instrumental in the development of novel vaccines and therapeutics. The goal of this review is to summarize our current understanding of the pathogenesis of coronavirus disease 2019 (COVID-19) and the pathologic features that can be observed in several currently available animal models. Knowledge gained from studying these animal models of SARS-CoV-2 infection can help inform appropriate model selection for disease modelling as well as for vaccine and therapeutic developments.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"The role of HDAC6 in enhancing macrophage autophagy via the autophagolysosomal pathway to alleviate legionella pneumophila-induced pneumonia.","authors":"Minjia Chen, Xiuqin Cao, Ronghui Zheng, Haixia Chen, Ruixia He, Hao Zhou, Zhiwei Yang","doi":"10.1080/21505594.2024.2327096","DOIUrl":"10.1080/21505594.2024.2327096","url":null,"abstract":"<p><p><i>Legionella pneumophila</i> (<i>L. pneumophila</i>) is a prevalent pathogenic bacterium responsible for significant global health concerns. Nonetheless, the precise pathogenic mechanisms of <i>L. pneumophila</i> have still remained elusive. Autophagy, a direct cellular response to <i>L. pneumophila</i> infection and other pathogens, involves the recognition and degradation of these invaders in lysosomes. Histone deacetylase 6 (HDAC6), a distinctive member of the histone deacetylase family, plays a multifaceted role in autophagy regulation. This study aimed to investigate the role of HDAC6 in macrophage autophagy via the autophagolysosomal pathway, leading to alleviate <i>L. pneumophila</i>-induced pneumonia. The results revealed a substantial upregulation of HDAC6 expression level in murine lung tissues infected by <i>L. pneumophila</i>. Notably, mice lacking HDAC6 exhibited a protective response against <i>L. pneumophila</i>-induced pulmonary tissue inflammation, which was characterized by the reduced bacterial load and diminished release of pro-inflammatory cytokines. Transcriptomic analysis has shed light on the regulatory role of HDAC6 in <i>L. pneumophila</i> infection in mice, particularly through the autophagy pathway of macrophages. Validation using <i>L. pneumophila</i>-induced macrophages from mice with HDAC6 gene knockout demonstrated a decrease in cellular bacterial load, activation of the autophagolysosomal pathway, and enhancement of cellular autophagic flux. In summary, the findings indicated that HDAC6 knockout could lead to the upregulation of p-ULK1 expression level, promoting the autophagy-lysosomal pathway, increasing autophagic flux, and ultimately strengthening the bactericidal capacity of macrophages. This contributes to the alleviation of <i>L. pneumophila</i>-induced pneumonia.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Emergence and circulation of enterovirus B species in infants in southern China: A multicenter retrospective analysis.","authors":"Xiaohan Yang, Yudan Wu, Hongyu Zhao, Pan Liu, Lihua Liang, Aihua Yin","doi":"10.1080/21505594.2024.2329569","DOIUrl":"10.1080/21505594.2024.2329569","url":null,"abstract":"<p><strong>Background: </strong>Enteroviruses (EV) are common and can cause severe diseases, particularly in young children. However, the information of EV infection in infants in China is limited due to the vast population size and extensive geographical area of the country. Here, we conducted a retrospective multicenter analysis of available EV data to assess the current epidemiological situation in the infant population in southern China.</p><p><strong>Methods: </strong>The study enrolled infants with suspected EV infection from 34 hospitals across 12 cities in southern China between 2019 to 2022, and the confirmation of EV was done using RT-PCR and VP1 gene sequencing.</p><p><strong>Results: </strong>Out of 1221 infants enrolled, 330 (27.03%) were confirmed as EV-infected. Of these, 260 (78.79%) were newborns aged 0-28 days. The EV belonged to three species: EV-B (80.61%), EV-A (11.82%), and human rhinovirus (7.58%). Newborns were more susceptible to EV-B than older infants (<i>p</i> < 0.001). Within EV-B, we identified 15 types, with coxsackievirus (CV) B3 (20.91%), echovirus (E) 11 (19.70%), and E18 (16.97%) being the most common. The predominant EV types changed across different years. EV infection in infants followed a seasonal pattern, with a higher incidence from May to August. Furthermore, perinatal mother-to-child EV transmission in 12 mother-newborn pairs were observed.</p><p><strong>Conclusion: </strong>Our study is the first to demonstrate the emergence and widespread circulation of EV-B species, mainly CVB3, E11, and E18, in southern China, primarily affecting young infants. This research provides valuable insights for future epidemic assessment, prediction, as well as the elimination of mother-to-child transmission.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Humoral responses to multiple SARS-CoV-2 variants after two doses of vaccine in kidney transplant patients.","authors":"Pin-Xian Du, Shen-Shin Chang, Tzong-Shiann Ho, Hsi-Chang Shih, Pei-Shan Tsai, Guan-Da Syu","doi":"10.1080/21505594.2024.2351266","DOIUrl":"10.1080/21505594.2024.2351266","url":null,"abstract":"<p><p><b>Background:</b> The COVID-19 pandemic has led to millions of fatalities globally. Kidney transplant (KT) patients, given their comorbidities and under immunosuppressant drugs, are identified as a high-risk group. Though vaccination remains pivotal for pandemic control, some studies indicate that KT exhibits diminished immune reactions to SARS-CoV-2 vaccines. Therefore, evaluating the vaccine responses in KT, especially the humoral responses against emergent variants is crucial.<b>Methods:</b> We developed a multiplexed SARS-CoV-2 variant protein microarray, incorporating the extracellular domain (ECD) and the receptor binding domain (RBD) of the spike proteins from the variants. This was employed to investigate the collective humoral responses after administering two doses of mRNA-1273 and AZD1222 vaccines in KT under immunosuppressive drugs and in healthy controls.<b>Results:</b> After two doses of either mRNA-1273 or AZD1222, the KT generally showed lower surrogate neutralizing and total antibodies against spike ECD in multiple variants compared to healthy controls. Although two doses of mRNA-1273 induced 1.5-2 fold more surrogate neutralizing and total antibodies than AZD1222 in healthy controls, the KT subjects with two doses of mRNA-1273 generally exhibited higher surrogate neutralizing but similar total antibodies against spike ECD in multiple variants. There were moderate to high correlations between the surrogate neutralizing and total antibodies against spike ECDs.<b>Conclusion:</b> This study offers pivotal insights into the relative vulnerability of KT concerning humoral immunity and the evolving mutations of SARS-CoV-2. Such findings are useful for evaluating vaccine responses and recommending vaccine episodes for KT.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Norepinephrine may promote the progression of <i>Fusobacterium nucleatum</i> related colorectal cancer via quorum sensing signalling.","authors":"Xinhao Du, Zhenzhen Tang, Li Yan, Ling Zhang, Qiao Zheng, Xianghao Zeng, Qing Hu, Qian Tian, Lanfan Liang, Xinyu Zhao, Jun Li, Ming Zhao, Xiangsheng Fu","doi":"10.1080/21505594.2024.2350904","DOIUrl":"10.1080/21505594.2024.2350904","url":null,"abstract":"<p><p><i>Fusobacterium nucleatum (F. nucleatum)</i> is closely correlated with tumorigenesis in colorectal cancer (CRC). We aimed to investigate the effects of host norepinephrine on the carcinogenicity of <i>F. nucleatum</i> in CRC and reveal the underlying mechanism. The results revealed that both norepinephrine and bacterial quorum sensing (QS) molecule auto-inducer-2 (AI-2) were positively associated with the progression of <i>F. nucleatum</i> related CRC (<i>p</i> < 0.01). <i>In vitro</i> studies, norepinephrine induced upregulation of QS-associated genes and promoted the virulence and proliferation of <i>F. nucleatum</i>. Moreover, chronic stress significantly increased the colon tumour burden of Apc^Min/+ mice infected with <i>F. nucleatum</i> (<i>p</i> < 0.01), which was decreased by a catecholamine inhibitor (<i>p</i> < 0.001). Our findings suggest that stress-induced norepinephrine may promote the progression of <i>F. nucleatum</i> related CRC via bacterial QS signalling. These preliminary data provide a novel strategy for the management of pathogenic bacteria by targeting host hormones-bacterial QS inter-kingdom signalling.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Simulating the clinical manifestations and disease progression of human sepsis: A monobacterial injection approach for animal modeling.","authors":"Xuanwen Ru, Simiao Chen, Danlei Chen, Qingyi Shao, Wenxia Shao, Qing Ye","doi":"10.1080/21505594.2024.2395835","DOIUrl":"10.1080/21505594.2024.2395835","url":null,"abstract":"<p><p>Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with great clinical heterogeneity, high morbidity, and high mortality. At the same time, there are many kinds of infection sources, the pathophysiology is very complex, and the pathogenesis has not been fully elucidated. An ideal animal model of sepsis can accurately simulate clinical sepsis and promote the development of sepsis-related pathogenesis, treatment methods, and prognosis. The existing sepsis model still uses the previous Sepsis 2.0 modelling standard, which has some problems, such as many kinds of infection sources, poor repeatability, inability to take into account single-factor studies, and large differences from clinical sepsis patients. To solve these problems, this study established a new animal model of sepsis. The model uses intravenous tail injection of a single bacterial strain, simplifying the complexity of multibacterial infection, and effectively solving the above problems.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"<i>Helicobacter pylori</i> East Asian type CagA hijacks more SHIP2 by its EPIYA-D motif to potentiate the oncogenicity.","authors":"Xiaofei Ji, Qianwen Wu, Xinying Cao, Shuzhen Liu, Jianhui Zhang, Si Chen, Jiangfan Shan, Ying Zhang, Boqing Li, Huilin Zhao","doi":"10.1080/21505594.2024.2375549","DOIUrl":"10.1080/21505594.2024.2375549","url":null,"abstract":"<p><p>CagA is a significant oncogenic factor injected into host cells by <i>Helicobacter pylori</i>, which is divided into two subtypes: East Asian type (CagA^E), characterized by the EPIYA-D motif, and western type (CagA^W), harboring the EPIYA-C motif. CagA^E has been reported to have higher carcinogenicity than CagA^W, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagA^E. Co-Immunoprecipitation and Pull-down assays showed that CagA^E bind more SHIP2 than CagA^W. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagA^E to the plasma membrane catalyzes the conversion of PI(3,4,5)P₃ into PI(3,4)P₂. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagA^E and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagA^E and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagA^E into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagA^E hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of <i>H. pylori</i> CagA^E.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing K1-ST23 hypervirulent <i>Klebsiella pneumoniae</i>.","authors":"Jiankang Zhao, Danni Pu, Ziyao Li, Yulin Zhang, Xinmeng Liu, Xianxia Zhuo, Binghuai Lu, Bin Cao","doi":"10.1080/21505594.2024.2348251","DOIUrl":"10.1080/21505594.2024.2348251","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed at revealing the underlying mechanisms of the loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing hypervirulent <i>Klebsiella pneumoniae</i> (hvKp).</p><p><strong>Methods: </strong>Here we longitudinally recovered 3 non-carbapenemase-producing K1-ST23 hvKp strains at a one-month interval (KP29105, KP29499 and KP30086) from an elderly male. Antimicrobial susceptibility testing, whole genome sequencing, transcriptomic sequencing, gene cloning, plasmid conjugation, quantitative real-time PCR (qRT-PCR), and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) were conducted.</p><p><strong>Results: </strong>Among the 3 hvKp strains, KP29105 was resistant to the third- and fourth-generation cephalosporins, KP29499 acquired resistance to both ceftazidime-avibactam and carbapenems, while KP30086 restored its susceptibility to ceftazidime-avibactam, imipenem and meropenem but retained low-level resistance to ertapenem. KP29105 and KP29499 carried plasmid-encoded genes <i>bla</i>_CTX-M-15 and <i>bla</i>_CTX-M-71, respectively, but KP30086 lost both. Cloning of gene <i>bla</i>_CTX-M-71 and conjugation experiment of <i>bla</i>_CTX-M-71-carrying plasmid showed that the transformant and transconjugant were susceptible to ceftazidime-avibactam but had a more than 8-fold increase in MICs. Supplementation with an outer membrane permeabilizer could reduce the MIC of ceftazidime-avibactam by 32 folds, indicating that porins play a key role in ceftazidime-avibactam resistance. The OmpK35 of the 3 isolates was not expressed, and the OmpK36 of KP29499 and KP30086 had a novel amino acid substitution (L359R). SDS-PAGE and qRT-PCR showed that the expression of porin OmpK36 of KP29499 and KP30086 was significantly down-regulated compared with KP29105.</p><p><strong>Conclusions: </strong>In summary, we reported the rare ceftazidime-avibactam resistance in a non-carbapenemase-producing hvKp strain. Resistance plasmid carrying <i>bla</i>_CTX-M-71 and mutated OmpK36 had a synergetic effect on the resistance.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11067985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}