International Journal of Medical Microbiology最新文献

{"title":"Effects of resveratrol on macrophages after phagocytosis of Candida glabrata","authors":"Zong-Han Chen ,&nbsp;Meng Guan ,&nbsp;Wei-Jia Zhao","doi":"10.1016/j.ijmm.2023.151589","DOIUrl":"10.1016/j.ijmm.2023.151589","url":null,"abstract":"<div><p><em>Candida glabrata</em> is believed to be the underlying cause of many human ailments, including oral, gastrointestinal, and vaginal disorders. <em>C. glabrata</em>-caused deep-seated infections, coupled with its resistance to antifungal drugs, may contribute to a high mortality rate. Resveratrol is a polyphenol and can achieve better therapeutic effects when administered in combination with micafungin, but the underlying molecular mechanisms remain unknown. Here, we investigate the effects of varying doses of resveratrol on the proliferation, apoptosis, and activity of macrophages, which were co-cultured with micafungin-pretreated <em>C. glabrata</em>. Resveratrol can restore the decreased proliferative activity of macrophages caused by the phagocytosis of <em>C. glabrata</em>. Further investigations demonstrated that this restoration ability exhibited a dose-dependent manner, reaching the highest level at 200 µM of resveratrol. Resveratrol tended to be more effective in inhibiting macrophage apoptosis and reducing reactive oxygen species (ROS) levels with concentration increases. In addition, at medium concentrations, resveratrol may down-regulate the expression of most inflammatory cytokines, whereas at high concentrations, it started to exert pro-inflammatory functions by up-regulating their expressions. Macrophages may shift from an anti-inflammatory (M2) phenotype to an inflammatory (M1) phenotype by resveratrol at 200 µM, and from M1 to M2 at 400 µM. Our research shows that resveratrol with micafungin are effective in treating <em>C. glabrata</em> infections. The resveratrol-micafungin combination can reduce the production of ROS, and promote the proliferation, inhibit the apoptosis, and activate the polarization of macrophages in a dose-dependent manner. This study offers insights into how this combination works and may provide possible direction for further clinical application of the combination.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"313 6","pages":"Article 151589"},"PeriodicalIF":4.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422123000176/pdfft?md5=10c10801df9fb875840599bbe8fa302a&pid=1-s2.0-S1438422123000176-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720367","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":"Polydatin alleviates mycoplasma pneumoniae-induced injury via inhibition of Caspase-1/GSDMD-dependent pyroptosis","authors":"Yiliu Chen ,&nbsp;Yonghong Jiang ,&nbsp;Xiuxiu Liu,&nbsp;Xiufeng Chen,&nbsp;Qiuyue Fan,&nbsp;Zhen Xiao","doi":"10.1016/j.ijmm.2023.151586","DOIUrl":"10.1016/j.ijmm.2023.151586","url":null,"abstract":"<div><p>Mycoplasma pneumoniae (MP) is one of the main pathogens causing community acquired pneumonia (CAP) in children and adults. Previous pharmacological and clinical studies have shown that Polydatin (PD) exerts anti-inflammatory action by conferring protective benefit in MP pneumonia. However, the mechanism underlying the of PD on MP infection remains unclear. It was found that PD alleviated MP-induced injury by inhibiting caspase-1/gasdermin D (GSDMD)-mediated epithelial pyroptosis. The results demonstrated that PD inhibited the transformation of GSDMD to N-terminal gasdermin-N (GSDMD-N) by decreasing caspase-1 activation, as well as suppressed the formation and secretion of interleukin-1β (IL-1β) and interleukin-18 (IL-18), reversed Na, K-ATPase reduction, and suppressed LDH release both in vitro and vivo. Taken together, epithelial pyroptosis in BEAS‐2B cells and lung injury in mice were prevented by PD. In conclusion, PD suppressed pulmonary injury triggered by MP infection, by inhibiting the caspase-1/GSDMD-mediated epithelial pyroptosis signaling pathway. Thus, PD may be regarded as a potential therapy for MP-induced inflammation.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"313 5","pages":"Article 151586"},"PeriodicalIF":4.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41179181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic and genotypic discrimination of Francisella tularensis ssp. holarctica clades","authors":"Kristin Köppen ,&nbsp;Kerstin Rydzewski ,&nbsp;Joerg Doellinger ,&nbsp;Kerstin Myrtennäs ,&nbsp;Mats Forsman ,&nbsp;Sandra Appelt ,&nbsp;Holger Scholz ,&nbsp;Klaus Heuner","doi":"10.1016/j.ijmm.2023.151583","DOIUrl":"10.1016/j.ijmm.2023.151583","url":null,"abstract":"<div><p><em>Francisella tularensis</em> is the causative agent of tularemia, a zoonotic disease with a wide host range. <em>F. tularensis</em> ssp. <em>holarctica</em> (<em>Fth</em>) is of clinical relevance for European countries, including Germany. Whole genome sequencing methods, including canonical Single Nucleotide Polymorphism (canSNP) typing and whole genome SNP typing, have revealed that European <em>Fth</em> strains belong to a few monophyletic populations. The majority of German <em>Fth</em> isolates belong to two basal phylogenetic clades B.6 (biovar I) and B.12 (biovar II). Strains of B.6 and B.12 seem to differ in their pathogenicity, and it has been shown that strains of biovar II are resistant against erythromycin. In this study, we present data corroborating our previous data demonstrating that basal clade B.12 can be divided into clades B.71 and B.72. By applying phylogenetic whole genome analysis as well as proteome analysis, we could verify that strains of these two clades are distinct from one another. This was confirmed by measuring the intensity of backscatter light on bacteria grown in liquid media. Strains belonging to clades B.6, B.71 or B.72 showed clade-specific backscatter growth curves. Furthermore, we present the whole genome sequence of strain A-1341, as a reference genome of clade B.71, and whole proteomes comparison of <em>Fth</em> strains belonging to clades B.6, B.71 and B.72. Further research is necessary to investigate phenotypes and putative differences in pathogenicity of the investigated different clades of <em>Fth</em> to better understand the relationship between observed phenotypes, pathogenicity and distribution of <em>Fth</em> strains.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"313 4","pages":"Article 151583"},"PeriodicalIF":4.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9972997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate activation of human neutrophils and neutrophil-like cells by the pro-inflammatory bacterial metabolite ADP-heptose and Helicobacter pylori","authors":"Larissa Faass ,&nbsp;Martina Hauke ,&nbsp;Saskia C. Stein ,&nbsp;Christine Josenhans","doi":"10.1016/j.ijmm.2023.151585","DOIUrl":"10.1016/j.ijmm.2023.151585","url":null,"abstract":"<div><p>Lipopolysaccharide inner core heptose metabolites, including ADP-heptose, play a substantial role in the activation of cell-autonomous innate immune responses in eukaryotic cells, via the ALPK1-TIFA signaling pathway, as demonstrated for various pathogenic bacteria. The important role of LPS heptose metabolites during <em>Helicobacter pylori</em> infection of the human gastric niche has been demonstrated for gastric epithelial cells and macrophages, while the role of heptose metabolites on human neutrophils has not been investigated. In this study, we aimed to gain a better understanding of the activation potential of bacterial heptose metabolites for human neutrophil cells. To do so, we used pure ADP-heptose and, as a bacterial model, <em>H. pylori</em>, which can transport heptose metabolites into the human host cell via the Cag Type 4 Secretion System (CagT4SS). Main questions were how bacterial heptose metabolites impact on the pro-inflammatory activation, alone and in the bacterial context, and how they influence maturation of human neutrophils. Results of the present study demonstrated that neutrophils respond with high sensitivity to pure heptose metabolites, and that global regulation networks and neutrophil maturation are influenced by heptose exposure. Furthermore, activation of human neutrophils by live <em>H. pylori</em> is strongly impacted by the presence of LPS heptose metabolites and the functionality of its CagT4SS. Similar activities were determined in cell culture neutrophils of different maturation states and in human primary neutrophils. In conclusion, we demonstrated that specific heptose metabolites or bacteria producing heptoses exhibit a strong activity on cell-autonomous innate responses of human neutrophils.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"313 4","pages":"Article 151585"},"PeriodicalIF":4.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9977343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat shock protein 70 is involved in polaprezinc driven cell protection against Helicobacter pylori-induced injury","authors":"Fansen Meng ,&nbsp;Siying Zhu ,&nbsp;Meiliang Gong ,&nbsp;Hongjin Tao ,&nbsp;Weihua Wang ,&nbsp;Gangshi Wang","doi":"10.1016/j.ijmm.2023.151582","DOIUrl":"10.1016/j.ijmm.2023.151582","url":null,"abstract":"<div><p>Polaprezinc (PZ) plays a role in the protection of gastric mucosa and inhibiting <em>Helicobacter pylori</em> (<em>H. pylori</em>) growth in vitro. The objective of this study was to determine the protective effects of PZ on human gastric epithelial cells (GES-1) against <em>H. pylori</em>-induced damage, while also examining heat shock protein 70 (HSP70) as a potential underlying factor in this protection. Our findings revealed that PZ exerted bactericidal effects against <em>H. pylori</em> strains. We also observed that PZ mitigated the <em>H. pylori</em>-induced damage to GES-1 cells by increasing cell viability, reducing LDH release, and decreasing the secretion of pro-inflammatory factors such as MCP-1 and IL-6. Co-culturing PZ with GES-1 cells significantly up-regulated the GES-1 HSP70 expression in both a time and dose-dependent manner. Pre-incubating (for 12 h) or co-culturing (for 24 h) GES-1 cells with PZ reversed the down-regulation of HSP70 in GES-1 cells caused by <em>H. pylori</em> infection. However, when quercetin was used to inhibit the up-regulation of HSP70 in GES-1 cells, the protective effect of PZ on GES-1 cells was significantly reduced. Based on the results of this study, PZ exhibits a protective role on GES-1 cells against <em>H. pylori</em> injury, as well as a direct bactericidal effect on <em>H. pylori</em>. HSP70 is involved in the PZ-driven host cell protection against <em>H. pylori</em> injury. These findings provide insight into alternative strategies for <em>H. pylori</em> treatment.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"313 3","pages":"Article 151582"},"PeriodicalIF":4.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal relationship between the gut microbiota variation and diversity and gut graft-versus-host disease (GVHD) following pediatric allogeneic hematopoietic cell transplantation (HCT) – Case series","authors":"Ashley N. Gray ,&nbsp;Nicole H. Tobin ,&nbsp;Theodore B. Moore ,&nbsp;Fan Li ,&nbsp;Grace M. Aldrovandi","doi":"10.1016/j.ijmm.2023.151580","DOIUrl":"10.1016/j.ijmm.2023.151580","url":null,"abstract":"<div><p>Allogeneic Hematopoietic Cell Transplantation (HCT) offers children with life-threatening diseases a chance at survival. Complications from graft-versus-host disease (GVHD, Stages 0–4) represent a significant cause of morbidity and mortality which has been recently associated with gut dysbiosis the adult HCT population. Here, our objective was to conduct a prospective, longitudinal cohort study in nine pediatric allogeneic HCT participants by collecting longitudinally post-HCT stool specimens up to 1 year. Stool microbiota analyses showed that allogeneic HCT and antibiotic therapy lead to acute shifts in the diversity of the gut microbiota with those experiencing stages 3–4 gut GVHD having significantly greater microbiota variation over time when compared to control participants (p = 0.007). Pre-HCT microbiota diversity trended towards an inverse relationship with gut microbiota stability over time, however, this did not reach statistical significance (p = 0.05). Future large prospective studies are necessary to elucidate the mechanisms underlying these dynamic changes in the gut microbiota following pediatric allogeneic HCT.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"313 3","pages":"Article 151580"},"PeriodicalIF":4.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9649655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasmodium falciparum rhoptry neck protein 4 has conserved regions mediating interactions with receptors on human erythrocytes and hepatocyte membrane","authors":"Fredy A. Pulido-Quevedo ,&nbsp;Gabriela Arévalo-Pinzón ,&nbsp;Jeimmy J. Castañeda-Ramírez ,&nbsp;Adriana Barreto-Santamaría ,&nbsp;Manuel E. Patarroyo ,&nbsp;Manuel A. Patarroyo","doi":"10.1016/j.ijmm.2023.151579","DOIUrl":"10.1016/j.ijmm.2023.151579","url":null,"abstract":"<div><p><em>Plasmodium falciparum</em>-related malaria represents a serious worldwide public health problem due to its high mortality rates. <em>P. falciparum</em> expresses rhoptry neck protein 4 (<em>Pf</em>RON4) in merozoite and sporozoite rhoptries, it participates in tight junction-TJ formation via the AMA-1/RON complex and is refractory to complete genetic deletion. Despite this, which <em>Pf</em>RON4 key regions interact with host cells remain unknown; such information would be useful for combating falciparum malaria. Thirty-two RON4 conserved region-derived peptides were chemically synthesised for determining and characterising <em>Pf</em>RON4 regions having high host cell binding affinity (high activity binding peptides or HABPs). Receptor-ligand interaction/binding assays determined their specific binding capability, the nature of their receptors and their ability to inhibit in vitro parasite invasion. Peptides 42477, 42479, 42480, 42505 and 42513 had greater than 2% erythrocyte binding activity, whilst peptides 42477 and 42480 specifically bound to HepG2 membrane, both of them having micromolar and submicromolar range dissociation constants (<em>Kd)</em>. Cell-peptide interaction was sensitive to treating erythrocytes with trypsin and/or chymotrypsin and HepG2 with heparinase I and chondroitinase ABC, suggesting protein-type (erythrocyte) and heparin and/or chondroitin sulphate proteoglycan receptors (HepG2) for <em>Pf</em>RON4. Erythrocyte invasion inhibition assays confirmed HABPs’ importance during merozoite invasion. <em>Pf</em>RON4 800–819 (42477) and 860–879 (42480) regions specifically interacted with host cells, thereby supporting their inclusion in a subunit-based, multi-antigen, multistage anti-malarial vaccine.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"313 3","pages":"Article 151579"},"PeriodicalIF":4.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9640718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical evaluation of 2-[18F]fluorodeoxysorbitol as a tracer for targeted imaging of Enterobacterales infection","authors":"Lisanne M. Braams ,&nbsp;Jürgen W.A. Sijbesma ,&nbsp;Hendrikus H. Boersma ,&nbsp;Jan Maarten van Dijl ,&nbsp;Philip H. Elsinga ,&nbsp;Andor W.J.M. Glaudemans ,&nbsp;Riemer H.J.A. Slart ,&nbsp;Marleen van Oosten","doi":"10.1016/j.ijmm.2023.151581","DOIUrl":"https://doi.org/10.1016/j.ijmm.2023.151581","url":null,"abstract":"<div><p>Fluorine-18-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (¹⁸F-FDG-PET) is widely used for the detection of inflammatory and infectious diseases. Although this modality has proven to be a useful diagnostic tool, reliable distinction of bacterial infection from sterile inflammation or even from a malignancy remains challenging. Therefore, there is a need for bacteria-specific tracers for PET imaging that facilitate a reliable distinction of bacterial infection from other pathology. The present study was aimed at exploring the potential of 2-[¹⁸F]-fluorodeoxysorbitol ([¹⁸F]FDS) as a tracer for detection of <em>Enterobacterales</em> infections. Sorbitol is a sugar alcohol that is commonly metabolized by bacteria of the <em>Enterobacterales</em> order, but not by mammalian cells, which makes it an attractive candidate for targeted bacterial imaging. The latter is important in view of the serious clinical implications of infections caused by <em>Enterobacterales.</em> Here we demonstrate that sorbitol-based PET can be applied to detect a broad range of clinical bacterial isolates not only in vitro, but also in blood and ascites samples from patients suffering from <em>Enterobacterales</em> infections. Notably, the possible application of [¹⁸F]FDS is not limited to <em>Enterobacterales</em> since <em>Pseudomonas aeruginosa</em> and <em>Corynebacterium jeikeium</em> also showed substantial uptake of this tracer. We conclude that [¹⁸F]FDS is a promising tracer for PET-imaging of infections caused by a group of bacteria that can cause serious invasive disease.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"313 3","pages":"Article 151581"},"PeriodicalIF":4.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49773813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of folate metabolism-related substances affecting Staphylococcus aureus infection","authors":"Qiyuan Jin ,&nbsp;Xiaolu Xie ,&nbsp;Yaxuan Zhai,&nbsp;Haifang Zhang","doi":"10.1016/j.ijmm.2023.151577","DOIUrl":"10.1016/j.ijmm.2023.151577","url":null,"abstract":"<div><p><em>Staphylococcus aureus</em> (<em>S. aureus</em>) is one of the critical clinical pathogens which can cause multiple diseases ranging from skin infections to fatal sepsis. <em>S. aureus</em> is generally considered to be an extracellular pathogen. However, more and more evidence has shown that <em>S. aureus</em> can survive inside various cells. Folate plays an essential role in multiple life activities, including the conversion of serine and glycine, the remethylation of homocysteine to methionine, and the <em>de novo</em> synthesis of purine /dTMP, et al. More and more studies reported that <em>S. aureus</em> intracellular infection requires the involvement of folate metabolism. This review focused on the mechanisms of folate metabolism and related substances affecting <em>S. aureus</em> infection. Loss of tetrahydrofolic acid (THF)-dependent dTMP directly inhibits the nucleotide synthesis pathway of the <em>S. aureus</em> due to <em>pabA</em> deficiency. Besides, trimethoprim-sulfamethoxazole (TMP/SMX), a potent antibiotic that treats <em>S. aureus</em> infections, interferes in the process of the folate mechanism and leads to the production of thymidine-dependent small-colony variants (TD-SCVs). In addition, <em>S. aureus</em> is resistant to lysostaphin in the presence of serine hydroxymethyltransferase (SHMT). We provide new insights for understanding the molecular pathogenesis of <em>S. aureus</em> infection.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"313 2","pages":"Article 151577"},"PeriodicalIF":4.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9261522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pretreatment with 3-methyladenine ameliorated Pseudomonas aeruginosa-induced acute pneumonia by inhibiting cell death of neutrophils in a mouse infection model","authors":"Lei Yue ,&nbsp;Han Cao ,&nbsp;Jialong Qi ,&nbsp;Jin Yuan ,&nbsp;Xin Wang ,&nbsp;Yunfei Wang ,&nbsp;Bin Shan ,&nbsp;Huaxin Ke ,&nbsp;Hua Li ,&nbsp;Ning Luan ,&nbsp;Cunbao Liu","doi":"10.1016/j.ijmm.2023.151574","DOIUrl":"10.1016/j.ijmm.2023.151574","url":null,"abstract":"<div><p><em>Pseudomonas aeruginosa</em> is one of the leading causes of nosocomial infections worldwide. Clinical isolates that are resistant to multiple antimicrobials make it intractable. The interactions between <em>P. aeruginosa</em> and host cell death have multiple effects on bacterial clearance and inflammation; however, the potential intervention effects remain to be defined. Herein, we demonstrated that intravenous administration of 3-methyladenine before, but not after, <em>P. aeruginosa</em> infection enhanced autophagy-independent survival, which was accompanied by a decrease in the bacterial load, alleviation of pathology and reduction in inflammatory cytokines, in an acute pneumonia mouse model. Interestingly, these beneficial effects were not dependent on neutrophil recruitment or phagocytosis, but on the enhanced killing capacity induced by inhibiting the cell death of 3-MA pretreated neutrophils. These findings demonstrate a novel protective role of 3-MA pretreatment in <em>P. aeruginosa</em>-induced acute pneumonia.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"313 2","pages":"Article 151574"},"PeriodicalIF":4.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9321422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}