Pub Date : 2025-06-01Epub Date: 2025-04-18DOI: 10.1016/j.ijmm.2025.151653
Imke Johanna Temme, Petya Berger, Ulrich Dobrindt, Alexander Mellmann
To investigate the adaptation of hybrid Escherichia coli to the intestinal and extraintestinal milieu, we compared our model hybrid Shiga toxin-producing (STEC) and uropathogenic (UPEC) E. coli O2:H6 strains with non-pathogenic E. coli and canonical UPEC and STEC strains in a carbon source utilization assay testing 95 common carbon sources under aerobic and anaerobic conditions. Comparison of anaerobic to aerobic growth showed a 2-fold decrease and 2.5-fold increase in the growth capacity and lag phase, respectively. While the UPEC and STEC/UPEC hybrids retained the utilization of several organic acids, amino acids, and peptides, the STEC and non-pathogenic strains relied almost exclusively on the utilization of sugar compounds under anaerobic conditions. Cluster analysis indicated a higher degree of difference and separation between all strains under aerobic conditions. The UPEC, hybrids, and STEC strain B2F1 showed high similarities in aerobic carbon utilization following growth patterns observed in previous phenotype assays. Additionally, we observed known UPEC virulence traits, such as the aerobic utilization of D-serine in our model STEC/UPEC hybrids. Combined, these findings suggest that the intestinal STEC/UPEC O2:H6 isolates originated from a UPEC background and acquired the ability to cause intestinal disease with the addition of Shiga toxin as a virulence factor.
{"title":"Carbon source utilization in hybrid Shiga toxin-producing and uropathogenic Escherichia coli indicates uropathogenic origin","authors":"Imke Johanna Temme, Petya Berger, Ulrich Dobrindt, Alexander Mellmann","doi":"10.1016/j.ijmm.2025.151653","DOIUrl":"10.1016/j.ijmm.2025.151653","url":null,"abstract":"<div><div>To investigate the adaptation of hybrid <em>Escherichia coli</em> to the intestinal and extraintestinal milieu, we compared our model hybrid Shiga toxin-producing (STEC) and uropathogenic (UPEC) <em>E. coli</em> O2:H6 strains with non-pathogenic <em>E. coli</em> and canonical UPEC and STEC strains in a carbon source utilization assay testing 95 common carbon sources under aerobic and anaerobic conditions. Comparison of anaerobic to aerobic growth showed a 2-fold decrease and 2.5-fold increase in the growth capacity and lag phase, respectively. While the UPEC and STEC/UPEC hybrids retained the utilization of several organic acids, amino acids, and peptides, the STEC and non-pathogenic strains relied almost exclusively on the utilization of sugar compounds under anaerobic conditions. Cluster analysis indicated a higher degree of difference and separation between all strains under aerobic conditions. The UPEC, hybrids, and STEC strain B2F1 showed high similarities in aerobic carbon utilization following growth patterns observed in previous phenotype assays. Additionally, we observed known UPEC virulence traits, such as the aerobic utilization of D-serine in our model STEC/UPEC hybrids. Combined, these findings suggest that the intestinal STEC/UPEC O2:H6 isolates originated from a UPEC background and acquired the ability to cause intestinal disease with the addition of Shiga toxin as a virulence factor.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"319 ","pages":"Article 151653"},"PeriodicalIF":4.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874457","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}
Pub Date : 2025-06-01Epub Date: 2025-05-22DOI: 10.1016/j.ijmm.2025.151657
Farah Alhussein , Dennis Held , Ahmad Mohamed Mostafa Abdrabou , Judith Fürstenberg , Ricarda Michels , Jamie Alex Maurer , Stefan Wagenpfeil , Sören L. Becker , Cihan Papan
Staphylococcus argenteus is a recently described member of the Staphylococcus aureus complex. Thus far, its frequency in clinical samples has been rarely described. Following an update of the commercially available matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) database (Bruker Daltonics) for pathogen identification, isolates from our S. aureus biobank were reanalysed for the detection of potentially misdiagnosed S. argenteus isolates. Additionally, we assessed whether phenotypical characteristics can be used to differentiate between S. aureus and S. argenteus in routine microbiological diagnostics. Among 505 investigated isolates, no S. argenteus or another member of the S. aureus complex were found. Furthermore, the morphological difference could not reliably distinguish between S. aureus and S. argenteus, as the latter was significantly more often missed by the staff in our study. Continuous surveillance of S. argenteus is essential to more accurately understand its epidemiology.
{"title":"Assessing potential misidentification of Staphylococcus argenteus as Staphylococcus aureus in clinical routine samples: A retrospective study","authors":"Farah Alhussein , Dennis Held , Ahmad Mohamed Mostafa Abdrabou , Judith Fürstenberg , Ricarda Michels , Jamie Alex Maurer , Stefan Wagenpfeil , Sören L. Becker , Cihan Papan","doi":"10.1016/j.ijmm.2025.151657","DOIUrl":"10.1016/j.ijmm.2025.151657","url":null,"abstract":"<div><div><em>Staphylococcus argenteus</em> is a recently described member of the <em>Staphylococcus aureus</em> complex. Thus far, its frequency in clinical samples has been rarely described. Following an update of the commercially available matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) database (Bruker Daltonics) for pathogen identification, isolates from our <em>S. aureus</em> biobank were reanalysed for the detection of potentially misdiagnosed <em>S. argenteus</em> isolates. Additionally, we assessed whether phenotypical characteristics can be used to differentiate between <em>S. aureus</em> and <em>S. argenteus</em> in routine microbiological diagnostics. Among 505 investigated isolates, no <em>S</em>. <em>argenteus</em> or another member of the <em>S</em>. <em>aureus</em> complex were found. Furthermore, the morphological difference could not reliably distinguish between <em>S. aureus</em> and <em>S. argenteus</em>, as the latter was significantly more often missed by the staff in our study. Continuous surveillance of <em>S. argenteus</em> is essential to more accurately understand its epidemiology.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"319 ","pages":"Article 151657"},"PeriodicalIF":4.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166756","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}
Pub Date : 2025-03-01Epub Date: 2024-12-26DOI: 10.1016/j.ijmm.2024.151642
Huan Liu , Xiaofeng Ma , Xuefeng Yang , Sujun Xiao , Shao Ouyang , Zhihao Hu , Zhixiang Zhou , Zhisheng Jiang
Background
The probiotic E. coli Nissle 1917 (EcN) alleviates the progression of various diseases, including colitis and tumors. However, EcN has not been studied in atherosclerosis. The study investigated the effects of EcN on atherosclerosis model mice and the potential mechanisms.
Methods
Mice in the high-fat diet (HFD) model were given EcN (1 × 109 CFU/g) or homocitrulline (150 mg/L) by oral administration for 12 weeks. The EcN + antibiotic group was set up to investigate the effects of EcN combined with antibiotics on gut microbiota. The control group was utilized as the negative control. Atherosclerosis status, pyroptosis, gut microbiota, and serum metabolites of mice were examined.
Results
EcN treatment alleviated HFD-caused atherosclerotic plaque and lipid droplet production. EcN treatment reversed HFD-induced increases in total cholesterol, triglycerides, and low-density lipoprotein levels and decreases in high-density lipoprotein levels. EcN inhibited the HFD-caused rise in the expression of pyroptosis-related indicators (cleaved Caspase 1, GSDMD-N, NLRP3, IL-18, and IL-1β). The antibiotics partially reversed the effects of EcN on the model mice, suggesting that EcN regulated pyroptosis in the model mice through gut microbiota. Probiotic bacteria, such as Lactobacillus and Muribaculum, were mainly enriched in the EcN and EcN + antibiotic groups, while Helicobacter, Alistipes, and Rikenella were depleted, suggesting that EcN and EcN + antibiotics could alleviate disorders of gut microbiota in the model mice. EcN reversed the trend of HFD-induced decrease of some metabolites, such as 2-methyl-5-nitroimidazole-1-ethanol, methionine sulfoxide, and shikimate 3-phosphate, and inhibited the increase of some metabolites, such as kynurenine, oxoadipate, and homocitrulline. In addition, homocitrulline showed the opposite effects of EcN in the model mice. Homocitrulline could bind to pyroptosis-related proteins to aggravate ox-LDL-induced endothelial cell pyroptosis.
Conclusion
EcN could alleviate atherosclerosis development by ameliorating HFD-induced disorders of gut microbiota and serum metabolites (such as homocitrulline) to alleviate pyroptosis, which may be associated with homocitrulline/Caspase 1/NLRP3/GSDMD axis. Our study lays the foundation for the development of promising drugs for atherosclerosis in the future.
{"title":"E. coli Nissle 1917 improves gut microbiota composition and serum metabolites to counteract atherosclerosis via the homocitrulline/Caspase 1/NLRP3/GSDMD axis","authors":"Huan Liu , Xiaofeng Ma , Xuefeng Yang , Sujun Xiao , Shao Ouyang , Zhihao Hu , Zhixiang Zhou , Zhisheng Jiang","doi":"10.1016/j.ijmm.2024.151642","DOIUrl":"10.1016/j.ijmm.2024.151642","url":null,"abstract":"<div><h3>Background</h3><div>The probiotic <em>E. coli Nissle 1917</em> (EcN) alleviates the progression of various diseases, including colitis and tumors. However, EcN has not been studied in atherosclerosis. The study investigated the effects of EcN on atherosclerosis model mice and the potential mechanisms.</div></div><div><h3>Methods</h3><div>Mice in the high-fat diet (HFD) model were given EcN (1 × 10<sup>9</sup> CFU/g) or homocitrulline (150 mg/L) by oral administration for 12 weeks. The EcN + antibiotic group was set up to investigate the effects of EcN combined with antibiotics on gut microbiota. The control group was utilized as the negative control. Atherosclerosis status, pyroptosis, gut microbiota, and serum metabolites of mice were examined.</div></div><div><h3>Results</h3><div>EcN treatment alleviated HFD-caused atherosclerotic plaque and lipid droplet production. EcN treatment reversed HFD-induced increases in total cholesterol, triglycerides, and low-density lipoprotein levels and decreases in high-density lipoprotein levels. EcN inhibited the HFD-caused rise in the expression of pyroptosis-related indicators (cleaved Caspase 1, GSDMD-N, NLRP3, IL-18, and IL-1β). The antibiotics partially reversed the effects of EcN on the model mice, suggesting that EcN regulated pyroptosis in the model mice through gut microbiota. Probiotic bacteria, such as <em>Lactobacillus</em> and <em>Muribaculum</em>, were mainly enriched in the EcN and EcN + antibiotic groups, while <em>Helicobacter</em>, <em>Alistipes</em>, and <em>Rikenella</em> were depleted, suggesting that EcN and EcN + antibiotics could alleviate disorders of gut microbiota in the model mice. EcN reversed the trend of HFD-induced decrease of some metabolites, such as 2-methyl-5-nitroimidazole-1-ethanol, methionine sulfoxide, and shikimate 3-phosphate, and inhibited the increase of some metabolites, such as kynurenine, oxoadipate, and homocitrulline. In addition, homocitrulline showed the opposite effects of EcN in the model mice. Homocitrulline could bind to pyroptosis-related proteins to aggravate ox-LDL-induced endothelial cell pyroptosis.</div></div><div><h3>Conclusion</h3><div>EcN could alleviate atherosclerosis development by ameliorating HFD-induced disorders of gut microbiota and serum metabolites (such as homocitrulline) to alleviate pyroptosis, which may be associated with homocitrulline/Caspase 1/NLRP3/GSDMD axis. Our study lays the foundation for the development of promising drugs for atherosclerosis in the future.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"Article 151642"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916117","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}
Pub Date : 2025-03-01Epub Date: 2025-02-05DOI: 10.1016/j.ijmm.2025.151647
Eliška Vrbová , Petra Pospíšilová , Eliška Dastychová , Martina Kojanová , Miluše Kreidlová , Daniela Vaňousová , Filip Rob , Přemysl Procházka , Alena Krchňáková , Vladimír Vašků , Radim Strnadel , Olga Faustmannová , Monika Dvořáková Heroldová , Ivana Kuklová , Hana Zákoucká , David Šmajs
Syphilis is a multistage sexually transmitted disease caused by Treponema pallidum ssp. pallidum (TPA). This study analyzed clinical samples collected from patients with a diagnosed syphilis infection from 2004–2022, isolated in the Czech Republic. Mucocutaneous swab samples (n = 543) from 543 patients were analyzed, and from these samples, 80.11 % (n = 435) were PCR positive, and 19.89 % (n = 108) were PCR negative for TPA DNA. Swabs were more often positive when collected from syphilis patients in the primary and secondary stages, compared to the latent or unknown stage. There was no significant difference in PCR positivity between the primary and secondary stages (p = 0.099). In IgM-positive patients, a statistically significant association with PCR-positivity was found in samples from seropositive (p = 0.033) and serodiscrepant (RPR negative) patients (p = 0.0006). When assessing our laboratory-defined cases of syphilis, the RPR, IgM, and PCR tests were similarly effective (within the range of 80.1–86.1 %). However, parallel testing with these methods was even more effective, i.e., RPR + PCR was 96.1 % effective and RPR + IgM + PCR was 97.8 % effective. A combination of RPR + PCR, or a combination of all three tests (RPR, IgM, and PCR) can therefore be used to reliably detect active syphilis cases, including reinfections. Our findings show that the reverse algorithm for detecting syphilis could be substantially improved by adding IgM and PCR testing.
{"title":"PCR-detection rates of T. pallidum ssp. pallidum in swab samples from the Czech Republic (2004–2022): Combined RPR, IgM, and PCR tests efficiently detect active syphilis","authors":"Eliška Vrbová , Petra Pospíšilová , Eliška Dastychová , Martina Kojanová , Miluše Kreidlová , Daniela Vaňousová , Filip Rob , Přemysl Procházka , Alena Krchňáková , Vladimír Vašků , Radim Strnadel , Olga Faustmannová , Monika Dvořáková Heroldová , Ivana Kuklová , Hana Zákoucká , David Šmajs","doi":"10.1016/j.ijmm.2025.151647","DOIUrl":"10.1016/j.ijmm.2025.151647","url":null,"abstract":"<div><div>Syphilis is a multistage sexually transmitted disease caused by <em>Treponema pallidum</em> ssp. <em>pallidum</em> (TPA). This study analyzed clinical samples collected from patients with a diagnosed syphilis infection from 2004–2022, isolated in the Czech Republic. Mucocutaneous swab samples (n = 543) from 543 patients were analyzed, and from these samples, 80.11 % (n = 435) were PCR positive, and 19.89 % (n = 108) were PCR negative for TPA DNA. Swabs were more often positive when collected from syphilis patients in the primary and secondary stages, compared to the latent or unknown stage. There was no significant difference in PCR positivity between the primary and secondary stages (p = 0.099). In IgM-positive patients, a statistically significant association with PCR-positivity was found in samples from seropositive (p = 0.033) and serodiscrepant (RPR negative) patients (p = 0.0006). When assessing our laboratory-defined cases of syphilis, the RPR, IgM, and PCR tests were similarly effective (within the range of 80.1–86.1 %). However, parallel testing with these methods was even more effective, i.e., RPR + PCR was 96.1 % effective and RPR + IgM + PCR was 97.8 % effective. A combination of RPR + PCR, or a combination of all three tests (RPR, IgM, and PCR) can therefore be used to reliably detect active syphilis cases, including reinfections. Our findings show that the reverse algorithm for detecting syphilis could be substantially improved by adding IgM and PCR testing.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"Article 151647"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349635","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}
Pub Date : 2025-03-01Epub Date: 2024-12-19DOI: 10.1016/j.ijmm.2024.151641
Jasmin Adam , Lisa-Marie Graf , Stefanie Westermann , David Voehringer , Sven Krappmann
Allergic bronchopulmonary aspergillosis is an incurable disease caused by the environmental mold Aspergillus fumigatus. This hypersensitivity pneumonia is characterized by an inflammatory type 2 immune response, accompanied by influx of eosinophils into the lung. To investigate the mode of action of eosinophils and the signaling events triggered by A. fumigatus, we used an in vitro coculture system of murine bone marrow-derived eosinophils confronted with conidia. Using small-molecule inhibitors, we identified signaling modules of eosinophils in the course of A. fumigatus confrontation. Eosinophils reduced fungal metabolic activity, but inhibition of relevant signaling modules did not affect this phenomenon upon eosinophil confrontation. A. fumigatus-induced secretion of Th2 cytokines and chemokines by eosinophils engaged proto-oncogene tyrosine-protein kinase Src, phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase as well as calcium cations and to some extent serine/threonine-protein kinase Akt and protein arginine deiminase 4. Src and PI3K kinases were also involved in A. fumigatus-mediated ROS production and regulation of eosinophils surface receptors. Especially Src and PI3K inhibitors prevented A. fumigatus-induced eosinophil activation. Taken together, identification of signaling cascades of eosinophils during their interaction with A. fumigatus provides relevant insights into the host-pathogen interaction in the context of ABPA to yield therapeutic perspectives.
{"title":"Signaling events driving Aspergillus fumigatus-induced eosinophil activation","authors":"Jasmin Adam , Lisa-Marie Graf , Stefanie Westermann , David Voehringer , Sven Krappmann","doi":"10.1016/j.ijmm.2024.151641","DOIUrl":"10.1016/j.ijmm.2024.151641","url":null,"abstract":"<div><div>Allergic bronchopulmonary aspergillosis is an incurable disease caused by the environmental mold <em>Aspergillus fumigatus.</em> This hypersensitivity pneumonia is characterized by an inflammatory type 2 immune response, accompanied by influx of eosinophils into the lung. To investigate the mode of action of eosinophils and the signaling events triggered by <em>A. fumigatus</em>, we used an <em>in vitro</em> coculture system of murine bone marrow-derived eosinophils confronted with conidia. Using small-molecule inhibitors, we identified signaling modules of eosinophils in the course of <em>A. fumigatus</em> confrontation. Eosinophils reduced fungal metabolic activity, but inhibition of relevant signaling modules did not affect this phenomenon upon eosinophil confrontation. <em>A. fumigatus</em>-induced secretion of Th2 cytokines and chemokines by eosinophils engaged proto-oncogene tyrosine-protein kinase Src, phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase as well as calcium cations and to some extent serine/threonine-protein kinase Akt and protein arginine deiminase 4. Src and PI3K kinases were also involved in <em>A. fumigatus</em>-mediated ROS production and regulation of eosinophils surface receptors. Especially Src and PI3K inhibitors prevented <em>A. fumigatus</em>-induced eosinophil activation. Taken together, identification of signaling cascades of eosinophils during their interaction with <em>A. fumigatus</em> provides relevant insights into the host-pathogen interaction in the context of ABPA to yield therapeutic perspectives.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"Article 151641"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886397","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}
Cardiovascular diseases, primarily caused by atherosclerosis, are a major public health concern worldwide. Atherosclerosis is characterized by chronic inflammation and lipid accumulation in the arterial wall, leading to plaque formation. In this process, macrophages play a crucial role by ingesting lipids and transforming into foam cells, which contribute to plaque instability and cardiovascular events. Recent studies have suggested that various pathogens are involved in the development of atherosclerosis, with Mycoplasma pneumoniae considered one of the potential candidates. Therefore, this study investigated whether this bacterium induces lipid accumulation in macrophages, which play a crucial role in the development of atherosclerosis, using the Raw264.7 model. Our findings revealed that M. pneumoniae infection promotes lipid droplet formation in macrophages. Glycerol 3-phosphate oxidase, GlpD, in the bacterium is involved in this process by producing reactive oxygen species, which in turn causes the oxidation of low-density lipoprotein. Furthermore, the significant increase in the expression of oxidized lipid receptors involved in the uptake of this oxidized lipid indicates that the bacteria promote lipid uptake in infected macrophages. These results suggest that M. pneumoniae has a direct pro-atherogenic effect, promoting the formation of atherosclerotic lesions through foam cell formation. Understanding the mechanisms by which M. pneumoniae influences atherosclerosis provides valuable insights for devising new therapeutic strategies for the prevention and management of cardiovascular diseases.
{"title":"Mycoplasma pneumoniae drives macrophage lipid uptake via GlpD-mediated oxidation, facilitating foam cell formation","authors":"Takeshi Yamamoto, Miki Okuno, Koichi Kuwano, Yoshitoshi Ogura","doi":"10.1016/j.ijmm.2025.151646","DOIUrl":"10.1016/j.ijmm.2025.151646","url":null,"abstract":"<div><div>Cardiovascular diseases, primarily caused by atherosclerosis, are a major public health concern worldwide. Atherosclerosis is characterized by chronic inflammation and lipid accumulation in the arterial wall, leading to plaque formation. In this process, macrophages play a crucial role by ingesting lipids and transforming into foam cells, which contribute to plaque instability and cardiovascular events. Recent studies have suggested that various pathogens are involved in the development of atherosclerosis, with <em>Mycoplasma pneumoniae</em> considered one of the potential candidates. Therefore, this study investigated whether this bacterium induces lipid accumulation in macrophages, which play a crucial role in the development of atherosclerosis, using the Raw264.7 model. Our findings revealed that <em>M. pneumoniae</em> infection promotes lipid droplet formation in macrophages. Glycerol 3-phosphate oxidase, GlpD, in the bacterium is involved in this process by producing reactive oxygen species, which in turn causes the oxidation of low-density lipoprotein. Furthermore, the significant increase in the expression of oxidized lipid receptors involved in the uptake of this oxidized lipid indicates that the bacteria promote lipid uptake in infected macrophages. These results suggest that <em>M. pneumoniae</em> has a direct pro-atherogenic effect, promoting the formation of atherosclerotic lesions through foam cell formation. Understanding the mechanisms by which <em>M. pneumoniae</em> influences atherosclerosis provides valuable insights for devising new therapeutic strategies for the prevention and management of cardiovascular diseases.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"Article 151646"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042877","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}
Currently, diagnosis of bacterial infections is based on culture, possibly followed by the amplification and sequencing (Sanger method) of the 16S rDNA - encoding gene when cultures are negative. Clinical metagenomics (CMg), i.e. the sequencing of a sample’s entire nucleic acids, may allow for the identification of bacteria not detected by conventional methods. Here, we tested the performance of CMg compared to 16S rDNA sequencing (Sanger) in 50 patients with suspected bacterial infection but negative cultures.
Methods
This is a prospective cohort study. Fifty patients (73 samples) with negative culture and a 16S rDNA sequencing demand (Sanger) were recruited from two sites. On the same samples, CMg (Illumina NextSeq) was also performed and compared to 16S rDNA Sanger sequencing. Bacteria were identified using MetaPhlAn4.
Results
Among the 73 samples, 20 (27 %, 17 patients) had a clinically relevant 16S rDNA Sanger sequencing result (used for patient management) while 11 (15 %, 9 patients) were considered contaminants. At the patient level, the sensitivity of CMg was 70 % (12/17) compared to 16S rDNA. In samples negative for 16S rDNA Sanger sequencing (n = 53), CMg identified clinically-relevant bacteria in 10 samples (19 %, 10 patients) with 14 additional bacteria.
Conclusions
CMg was not 100 % sensitive when compared to 16S, supporting that it may not be a suitable replacement. However, CMg did find additional bacteria in samples negative for 16S rDNA Sanger. CMg could therefore be positioned as a complementary to 16S rDNA Sanger sequencing.
{"title":"Comparison of clinical metagenomics with 16S rDNA Sanger sequencing for the bacteriological diagnosis of culture-negative samples","authors":"Camille d’Humières , Skerdi Haviari , Marie Petitjean , Laurène Deconinck , Signara Gueye , Nathan Peiffer-Smadja , Lynda Chalal , Naima Beldjoudi , Geoffrey Rossi , Yann Nguyen , Charles Burdet , Ségolène Perrineau , Diane Le Pluart , Roza Rahli , Michael Thy , Piotr Szychowiak , Xavier Lescure , Véronique Leflon-Guibout , Victoire de Lastours , Etienne Ruppé","doi":"10.1016/j.ijmm.2025.151650","DOIUrl":"10.1016/j.ijmm.2025.151650","url":null,"abstract":"<div><h3>Background</h3><div>Currently, diagnosis of bacterial infections is based on culture, possibly followed by the amplification and sequencing (Sanger method) of the 16S rDNA - encoding gene when cultures are negative. Clinical metagenomics (CMg), i.e. the sequencing of a sample’s entire nucleic acids, may allow for the identification of bacteria not detected by conventional methods. Here, we tested the performance of CMg compared to 16S rDNA sequencing (Sanger) in 50 patients with suspected bacterial infection but negative cultures.</div></div><div><h3>Methods</h3><div>This is a prospective cohort study. Fifty patients (73 samples) with negative culture and a 16S rDNA sequencing demand (Sanger) were recruited from two sites. On the same samples, CMg (Illumina NextSeq) was also performed and compared to 16S rDNA Sanger sequencing. Bacteria were identified using MetaPhlAn4.</div></div><div><h3>Results</h3><div>Among the 73 samples, 20 (27 %, 17 patients) had a clinically relevant 16S rDNA Sanger sequencing result (used for patient management) while 11 (15 %, 9 patients) were considered contaminants. At the patient level, the sensitivity of CMg was 70 % (12/17) compared to 16S rDNA. In samples negative for 16S rDNA Sanger sequencing (n = 53), CMg identified clinically-relevant bacteria in 10 samples (19 %, 10 patients) with 14 additional bacteria.</div></div><div><h3>Conclusions</h3><div>CMg was not 100 % sensitive when compared to 16S, supporting that it may not be a suitable replacement. However, CMg did find additional bacteria in samples negative for 16S rDNA Sanger. CMg could therefore be positioned as a complementary to 16S rDNA Sanger sequencing.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"Article 151650"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379409","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}
Pub Date : 2025-03-01Epub Date: 2024-12-31DOI: 10.1016/j.ijmm.2024.151643
Lisa Maria Kleine , Emmanuel Marx Kanu , Tobias Grebe , Desmond Mohamed Sesay , Henning Loismann , Maxwell Sesay , Tom Theiler , Viktoria Rudolf , Alexander Mellmann , Laura C. Kalkman , Martin P. Grobusch , Frieder Schaumburg
Background
Nasopharyngeal colonization with Staphylococcus aureus is a risk factor for subsequent infection. Isolates from colonization can therefore provide important information on virulence factors and antimicrobial resistance when data from clinical isolates are lacking. The aim of this study was to assess colonization rates, resistance patterns and selected virulence factors of S. aureus from rural Sierra Leone.
Methods
Residents of randomly selected houses in Masanga, Sierra Leone were included in a cross-sectional study (8–11/2023). Participants were tested for nasopharyngeal S. aureus colonization using selective culture media. Risk factors for colonization were documented in a standardized questionnaire. Isolates were genotyped and tested for antimicrobial susceptibility and selected virulence factors (e.g. Panton-Valentine leukocidin, capsular types).
Results
Of 300 participants (62.7 % females, median age: 16 years), 168 (56 %) were colonized with S. aureus-related complex; six participants carried two different S. aureus genotypes, resulting in a total number of 174 isolates. Resistance to penicillin was predominant (97.1 %, 169/174), followed by tetracycline (66.1 %, 115/174), co-trimoxazole (56.9 %, 99/174) and oxacillin (24.1 %, 42/174, all mecA-positive, mostly associated with ST8/PVL-negative). PVL gene was detected in 21.3 % of isolates (37/174) mainly associated with ST15 and ST152. Except for past use of antimicrobials (p = 0.019), no specific risk factors such as comorbidities including hemoglobin variants were associated with S. aureus nasopharyngeal colonization.
Conclusion
The prevalence of methicillin-resistant and PVL-positive methicillin-susceptible S. aureus (MRSA/MSSA) is high in a rural community of asymptomatic carriers in Sierra Leone. Measures to contain the spread of MRSA, also in the community, are needed.
{"title":"Nasopharyngeal carriage of Staphylococcus aureus in a rural population, Sierra Leone","authors":"Lisa Maria Kleine , Emmanuel Marx Kanu , Tobias Grebe , Desmond Mohamed Sesay , Henning Loismann , Maxwell Sesay , Tom Theiler , Viktoria Rudolf , Alexander Mellmann , Laura C. Kalkman , Martin P. Grobusch , Frieder Schaumburg","doi":"10.1016/j.ijmm.2024.151643","DOIUrl":"10.1016/j.ijmm.2024.151643","url":null,"abstract":"<div><h3>Background</h3><div>Nasopharyngeal colonization with <em>Staphylococcus aureus</em> is a risk factor for subsequent infection. Isolates from colonization can therefore provide important information on virulence factors and antimicrobial resistance when data from clinical isolates are lacking. The aim of this study was to assess colonization rates, resistance patterns and selected virulence factors of <em>S. aureus</em> from rural Sierra Leone.</div></div><div><h3>Methods</h3><div>Residents of randomly selected houses in Masanga, Sierra Leone were included in a cross-sectional study (8–11/2023). Participants were tested for nasopharyngeal <em>S. aureus</em> colonization using selective culture media. Risk factors for colonization were documented in a standardized questionnaire. Isolates were genotyped and tested for antimicrobial susceptibility and selected virulence factors (e.g. Panton-Valentine leukocidin, capsular types).</div></div><div><h3>Results</h3><div>Of 300 participants (62.7 % females, median age: 16 years), 168 (56 %) were colonized with <em>S. aureus-</em>related complex<em>;</em> six participants carried two different <em>S. aureus</em> genotypes, resulting in a total number of 174 isolates. Resistance to penicillin was predominant (97.1 %, 169/174), followed by tetracycline (66.1 %, 115/174), co-trimoxazole (56.9 %, 99/174) and oxacillin (24.1 %, 42/174, all <em>mecA</em>-positive, mostly associated with ST8/PVL-negative). PVL gene was detected in 21.3 % of isolates (37/174) mainly associated with ST15 and ST152. Except for past use of antimicrobials (p = 0.019), no specific risk factors such as comorbidities including hemoglobin variants were associated with <em>S. aureus</em> nasopharyngeal colonization.</div></div><div><h3>Conclusion</h3><div>The prevalence of methicillin-resistant and PVL-positive methicillin-susceptible <em>S. aureus</em> (MRSA/MSSA) is high in a rural community of asymptomatic carriers in Sierra Leone. Measures to contain the spread of MRSA, also in the community, are needed.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"Article 151643"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933443","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}
Pub Date : 2025-03-01Epub Date: 2025-03-05DOI: 10.1016/j.ijmm.2025.151651
Misti D. Finton , Roger Meisal , Davide Porcellato , Lin T. Brandal , Bjørn-Arne Lindstedt
The global rise of hybrid Escherichia coli (E. coli) is a major public health concern, as enhanced virulence from multiple pathotypes complicates the traditional E. coli classification system and challenges clinical diagnostics. Hybrid strains are particularly concerning as they can infect both intestinal and extraintestinal sites, complicating treatment and increasing the risk of severe disease. This study analyzed virulence-associated genes (VAGs) in 13 E. coli isolates from fecal samples of patients with symptoms of gastrointestinal (GI) infection in Norwegian hospitals and clinics. Whole genome sequencing (WGS) was conducted using Oxford Nanopore’s MinION and Illumina’s MiSeq platforms. Eleven strains harbored molecular diagnostic markers of atypical enteropathogenic E. coli (aEPEC), enteroinvasive E. coli (EIEC), Shiga toxin-producing E. coli (STEC), enterotoxigenic E. coli (ETEC), or typical enteropathogenic E. coli (tEPEC). Two of those isolates were identified as triple intestinal hybrids with molecular diagnostic markers for aEPEC, EIEC, and STEC. Notably, two isolates lacked any IPEC-specific molecular diagnostic markers, yet were suspected of causing the patient’s GI infection. Furthermore, genes associated with extraintestinal pathogenic E. coli (ExPEC)—including adhesins, toxins, protectins, siderophores, iron acquisition systems, and invasins—were identified in all the isolates. Thus, most of the isolates were classified as hybrid aEPEC/ExPEC, STEC/ExPEC, tEPEC/ExPEC, or aEPEC/EIEC/STEC/ExPEC. These findings emphasize the genomic plasticity of E. coli and highlight the need to revise the classification system for enteric pathogens.
{"title":"Comparative genomics of clinical hybrid Escherichia coli strains in Norway","authors":"Misti D. Finton , Roger Meisal , Davide Porcellato , Lin T. Brandal , Bjørn-Arne Lindstedt","doi":"10.1016/j.ijmm.2025.151651","DOIUrl":"10.1016/j.ijmm.2025.151651","url":null,"abstract":"<div><div>The global rise of hybrid <em>Escherichia coli</em> (<em>E. coli</em>) is a major public health concern, as enhanced virulence from multiple pathotypes complicates the traditional <em>E. coli</em> classification system and challenges clinical diagnostics. Hybrid strains are particularly concerning as they can infect both intestinal and extraintestinal sites, complicating treatment and increasing the risk of severe disease. This study analyzed virulence-associated genes (VAGs) in 13 <em>E. coli</em> isolates from fecal samples of patients with symptoms of gastrointestinal (GI) infection in Norwegian hospitals and clinics. Whole genome sequencing (WGS) was conducted using Oxford Nanopore’s MinION and Illumina’s MiSeq platforms. Eleven strains harbored molecular diagnostic markers of atypical enteropathogenic <em>E. coli</em> (aEPEC), enteroinvasive <em>E. coli</em> (EIEC), Shiga toxin-producing <em>E. coli</em> (STEC), enterotoxigenic <em>E. coli</em> (ETEC), or typical enteropathogenic <em>E. coli</em> (tEPEC). Two of those isolates were identified as triple intestinal hybrids with molecular diagnostic markers for aEPEC, EIEC, and STEC. Notably, two isolates lacked any IPEC-specific molecular diagnostic markers, yet were suspected of causing the patient’s GI infection. Furthermore, genes associated with extraintestinal pathogenic <em>E. coli</em> (ExPEC)—including adhesins, toxins, protectins, siderophores, iron acquisition systems, and invasins—were identified in all the isolates. Thus, most of the isolates were classified as hybrid aEPEC/ExPEC, STEC/ExPEC, tEPEC/ExPEC, or aEPEC/EIEC/STEC/ExPEC. These findings emphasize the genomic plasticity of <em>E. coli</em> and highlight the need to revise the classification system for enteric pathogens.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"Article 151651"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578573","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}
Pub Date : 2025-03-01Epub Date: 2025-01-06DOI: 10.1016/j.ijmm.2025.151645
Nahed Al Laham , Ahmed Al Afifi , Alexander Mellmann , Frieder Schaumburg
Background
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a difficult to treat organism owing to limited therapeutic options. So far, little is known about the molecular characteristics of CRKP in Palestine.
Objectives
The aim of this study was to investigate the antimicrobial resistance patterns, multilocus sequence types (ST) and resistance genes among clinical K. pneumoniae isolates from hospitalized patients in Gaza Strip, Palestine.
Methods
K. pneumoniae from blood cultures (n = 55) were collected at two hospitals in Gaza Strip (2023) and identified by MALDI-TOF-MS. Antimicrobial susceptibility testing was done using VITEK-2 automated systems. Carbapenemases were phenotypically detected. Whole genome sequencing (WGS) of all CRKP isolates was performed to assess determinants for carbapenem resistance and genotypes.
Results
Of all K. pneumoniae isolates, 40 % (n = 22/55) were CRKP. Among CRKP, cefiderocol showed the least resistance (46 %, n = 10/22) while ceftazidime/avibactam showed a synergistic effect with aztreonam (36 %, n = 8/22). The majority (86 %, n = 19/22) of CRKP carried metallo-β-lactamases, and only 9 % (n = 2/22) encoded OXA-48 carbapenemase. WGS of CRKP revealed that the predominant genotype is multilocus sequence type ST147 harboring blaNDM-5 and blaCTX-M-15.
Conclusion
The proportion of CRKP among all K. pneumoniae from bloodstream infection in Gaza Strip is high (40 %) and mainly associated with the blaNDM-5-positive high-risk clone ST147.
{"title":"Characterization of carbapenem-resistant Klebsiella pneumoniae from blood cultures in Gaza Strip hospitals, Palestine","authors":"Nahed Al Laham , Ahmed Al Afifi , Alexander Mellmann , Frieder Schaumburg","doi":"10.1016/j.ijmm.2025.151645","DOIUrl":"10.1016/j.ijmm.2025.151645","url":null,"abstract":"<div><h3>Background</h3><div>Carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) is a difficult to treat organism owing to limited therapeutic options. So far, little is known about the molecular characteristics of CRKP in Palestine.</div></div><div><h3>Objectives</h3><div>The aim of this study was to investigate the antimicrobial resistance patterns, multilocus sequence types (ST) and resistance genes among clinical <em>K. pneumoniae</em> isolates from hospitalized patients in Gaza Strip, Palestine.</div></div><div><h3>Methods</h3><div><em>K. pneumoniae</em> from blood cultures (n = 55) were collected at two hospitals in Gaza Strip (2023) and identified by MALDI-TOF-MS. Antimicrobial susceptibility testing was done using VITEK-2 automated systems. Carbapenemases were phenotypically detected. Whole genome sequencing (WGS) of all CRKP isolates was performed to assess determinants for carbapenem resistance and genotypes.</div></div><div><h3>Results</h3><div>Of all <em>K. pneumoniae</em> isolates, 40 % (n = 22/55) were CRKP. Among CRKP, cefiderocol showed the least resistance (46 %, n = 10/22) while ceftazidime/avibactam showed a synergistic effect with aztreonam (36 %, n = 8/22). The majority (86 %, n = 19/22) of CRKP carried metallo-β-lactamases, and only 9 % (n = 2/22) encoded OXA-48 carbapenemase. WGS of CRKP revealed that the predominant genotype is multilocus sequence type ST147 harboring <em>bla</em><sub>NDM-5</sub> and <em>bla</em><sub>CTX-M-15</sub>.</div></div><div><h3>Conclusion</h3><div>The proportion of CRKP among all <em>K. pneumoniae</em> from bloodstream infection in Gaza Strip is high (40 %) and mainly associated with the <em>bla</em><sub>NDM-5</sub>-positive high-risk clone ST147.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"318 ","pages":"Article 151645"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958167","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}
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