Umeå University's logo

umu.sePublications
Change search
Link to record
Permanent link

Direct link
Alternative names
Publications (10 of 119) Show all publications
Oscarsson, J., Bao, K., Shiratsuchi, A., Grossmann, J., Wolski, W., Aung, K. M., . . . Bostanci, N. (2024). Bacterial symbionts in oral niche use type VI secretion nanomachinery for fitness increase against pathobionts. iScience, Article ID 109650.
Open this publication in new window or tab >>Bacterial symbionts in oral niche use type VI secretion nanomachinery for fitness increase against pathobionts
Show others...
2024 (English)In: iScience, ISSN 2589-0042, article id 109650Article in journal (Refereed) In press
Abstract [en]

Microbial ecosystems experience spatial and nutrient restrictions, leading to the coevolution of cooperation and competition among cohabiting species. To increase their fitness for survival, bacteria exploit machinery to antagonizing rival species upon close contact. As such, the bacterial type VI secretion system (T6SS) nanomachinery, typically expressed by pathobionts, can transport proteins directly into eukaryotic or prokaryotic cells, consequently killing cohabiting competitors. Here we demonstrate first time that oral symbiont Aggregatibacter aphrophilus possesses a T6SS and can eliminate its close relative oral pathobiont Aggregatibacter actinomycetemcomitans using its T6SS. These findings bring newer the anti-bacterial prospects of symbionts against cohabiting pathobionts while introducing presence of an active T6SS in the oral cavity.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Pathobiont, aggregatibacter species, Type VI secretion system
National Category
Infectious Medicine Dentistry
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-223048 (URN)10.1016/j.isci.2024.109650 (DOI)
Funder
Swedish Research Council, 2022-010
Available from: 2024-04-09 Created: 2024-04-09 Last updated: 2024-04-10
Mushtaq, F., Nadeem, A., Yabrag, A., Bala, A., Karah, N., Zlatkov, N., . . . Ahmad, I. (2024). Colony phase variation switch modulates antimicrobial tolerance and biofilm formation in Acinetobacter baumannii. Microbiology Spectrum, 12(2), Article ID e02956-23.
Open this publication in new window or tab >>Colony phase variation switch modulates antimicrobial tolerance and biofilm formation in Acinetobacter baumannii
Show others...
2024 (English)In: Microbiology Spectrum, E-ISSN 2165-0497, Vol. 12, no 2, article id e02956-23Article in journal (Refereed) Published
Abstract [en]

Carbapenem-resistant Acinetobacter baumannii causes one of the most difficult-to-treat nosocomial infections. Polycationic drugs like polymyxin B or colistin and tetracycline drugs such as doxycycline or minocycline are commonly used to treat infections caused by carbapenem-resistant A. baumannii. Here, we show that a subpopulation of cells associated with the opaque/translucent colony phase variation by A. baumannii AB5075 displays differential tolerance to subinhibitory concentrations of colistin and tetracycline. Using a variety of microscopic techniques, we demonstrate that extracellular polysaccharide moieties mediate colistin tolerance to opaque A. baumannii at single-cell level and that mushroom-shaped biofilm structures protect opaque bacteria at the community level. The colony switch phenotype is found to alter several traits of A. baumannii, including long-term survival under desiccation, tolerance to ethanol, competition with Escherichia coli, and intracellular survival in the environmental model host Acanthamoeba castellanii. Additionally, our findings suggest that extracellular DNA associated with membrane vesicles can promote colony switching in a DNA recombinase-dependent manner.

Importance: As a WHO top-priority drug-resistant microbe, Acinetobacter baumannii significantly contributes to hospital-associated infections worldwide. One particularly intriguing aspect is its ability to reversibly switch its colony morphotype on agar plates, which has been remarkably underexplored. In this study, we employed various microscopic techniques and phenotypic assays to investigate the colony phase variation switch under different clinically and environmentally relevant conditions. Our findings reveal that the presence of a poly N-acetylglucosamine-positive extracellular matrix layer contributes to the protection of bacteria from the bactericidal effects of colistin. Furthermore, we provide intriguing insights into the multicellular lifestyle of A. baumannii, specifically in the context of colony switch variation within its predatory host, Acanthamoeba castellanii.

Place, publisher, year, edition, pages
American Society for Microbiology, 2024
Keywords
colisitin, opaque colony, translucent colony
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-221121 (URN)10.1128/spectrum.02956-23 (DOI)001141161500001 ()38205963 (PubMedID)2-s2.0-85184519514 (Scopus ID)
Funder
Swedish Research Council, 2020-06136Swedish Research Council, 2019-01720Swedish Research Council, 2018-02914Swedish Research Council, 2016-00968Swedish Research Council, 2019-00217The Kempe Foundations, SMK-1961The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IB2022-9222Swedish Cancer Society, 2017-419
Available from: 2024-02-20 Created: 2024-02-20 Last updated: 2024-02-20Bibliographically approved
Ahmad, I., Nadeem, A., Mushtaq, F., Zlatkov, N., Shahzad, M., Zavialov, A. V., . . . Uhlin, B. E. (2023). Csu pili dependent biofilm formation and virulence of Acinetobacter baumannii. npj Biofilms and Microbiomes, 9(1), Article ID 101.
Open this publication in new window or tab >>Csu pili dependent biofilm formation and virulence of Acinetobacter baumannii
Show others...
2023 (English)In: npj Biofilms and Microbiomes, E-ISSN 2055-5008, Vol. 9, no 1, article id 101Article in journal (Refereed) Published
Abstract [en]

Acinetobacter baumannii has emerged as one of the most common extensive drug-resistant nosocomial bacterial pathogens. Not only can the bacteria survive in hospital settings for long periods, but they are also able to resist adverse conditions. However, underlying regulatory mechanisms that allow A. baumannii to cope with these conditions and mediate its virulence are poorly understood. Here, we show that bi-stable expression of the Csu pili, along with the production of poly-N-acetyl glucosamine, regulates the formation of Mountain-like biofilm-patches on glass surfaces to protect bacteria from the bactericidal effect of colistin. Csu pilus assembly is found to be an essential component of mature biofilms formed on glass surfaces and of pellicles. By using several microscopic techniques, we show that clinical isolates of A. baumannii carrying abundant Csu pili mediate adherence to epithelial cells. In addition, Csu pili suppressed surface-associated motility but enhanced colonization of bacteria into the lungs, spleen, and liver in a mouse model of systemic infection. The screening of c-di-GMP metabolizing protein mutants of A. baumannii 17978 for the capability to adhere to epithelial cells led us to identify GGDEF/EAL protein AIS_2337, here denoted PdeB, as a major regulator of Csu pili-mediated virulence and biofilm formation. Moreover, PdeB was found to be involved in the type IV pili-regulated robustness of surface-associated motility. Our findings suggest that the Csu pilus is not only a functional component of mature A. baumannii biofilms but also a major virulence factor promoting the initiation of disease progression by mediating bacterial adherence to epithelial cells.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-218629 (URN)10.1038/s41522-023-00465-6 (DOI)38097635 (PubMedID)2-s2.0-85179677116 (Scopus ID)
Funder
Swedish Research Council, 2020-06136Swedish Research Council, 2020-06136Swedish Research Council, 2018-02914Swedish Research Council, 2022-04779The Kempe Foundations, SMK-1961The Kempe Foundations, SMK21-0076Umeå University, FS 2.1.6–1776-19Umeå University, 2021-2023The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)Swedish Cancer Society, 2017-419
Available from: 2023-12-27 Created: 2023-12-27 Last updated: 2023-12-27Bibliographically approved
Pu, L., Wang, J., Lu, Q., Nilsson, L., Philbrook, A., Pandey, A., . . . Chen, C. (2023). Dissecting the genetic landscape of GPCR signaling through phenotypic profiling in  C. elegans. Nature Communications, 14, Article ID 8410.
Open this publication in new window or tab >>Dissecting the genetic landscape of GPCR signaling through phenotypic profiling in  C. elegans
Show others...
2023 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 14, article id 8410Article in journal (Refereed) Published
Abstract [en]

G protein-coupled receptors (GPCRs) mediate responses to various extracellular and intracellular cues. However, the large number of GPCR genes and their substantial functional redundancy make it challenging to systematically dissect GPCR functions in vivo. Here, we employ a CRISPR/Cas9-based approach, disrupting 1654 GPCR-encoding genes in 284 strains and mutating 152 neuropeptide-encoding genes in 38 strains in C. elegans. These two mutant libraries enable effective deorphanization of chemoreceptors, and characterization of receptors for neuropeptides in various cellular processes. Mutating a set of closely related GPCRs in a single strain permits the assignment of functions to GPCRs with functional redundancy. Our analyses identify a neuropeptide that interacts with three receptors in hypoxia-evoked locomotory responses, unveil a collection of regulators in pathogen-induced immune responses, and define receptors for the volatile food-related odorants. These results establish our GPCR and neuropeptide mutant libraries as valuable resources for the C. elegans community to expedite studies of GPCR signaling in multiple contexts.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-217489 (URN)10.1038/s41467-023-44177-z (DOI)38110404 (PubMedID)2-s2.0-85180225404 (Scopus ID)
Funder
Swedish Research Council, 2018-02914Swedish Research Council, 2021-06602Swedish Research Council, 2018-02216
Note

Originally included in thesis in manuscript form. 

Available from: 2023-12-05 Created: 2023-12-05 Last updated: 2024-01-05Bibliographically approved
Farag, S., Francis, M. K., Gurung, J. M., Wai, S. N., Stenlund, H., Francis, M. S. & Nadeem, A. (2023). Macrophage innate immune responses delineate between defective translocon assemblies produced by Yersinia pseudotuberculosis YopD mutants. Virulence, 14(1), Article ID 2249790.
Open this publication in new window or tab >>Macrophage innate immune responses delineate between defective translocon assemblies produced by Yersinia pseudotuberculosis YopD mutants
Show others...
2023 (English)In: Virulence, ISSN 2150-5594, E-ISSN 2150-5608, Vol. 14, no 1, article id 2249790Article in journal (Refereed) Published
Abstract [en]

Translocon pores formed in the eukaryotic cell membrane by a type III secretion system facilitate the translocation of immune-modulatory effector proteins into the host cell interior. The YopB and YopD proteins produced and secreted by pathogenic Yersinia spp. harboring a virulence plasmid-encoded type III secretion system perform this pore-forming translocator function. We had previously characterized in vitro T3SS function and in vivo pathogenicity of a number of strains encoding sited-directed point mutations in yopD. This resulted in the classification of mutants into three different classes based upon the severity of the phenotypic defects. To investigate the molecular and functional basis for these defects, we explored the effectiveness of RAW 264.7 cell line to respond to infection by representative YopD mutants of all three classes. Signature cytokine profiles could separate the different YopD mutants into distinct categories. The activation and suppression of certain cytokines that function as central innate immune response modulators correlated well with the ability of mutant bacteria to alter anti-phagocytosis and programmed cell death pathways. These analyses demonstrated that sub-optimal translocon pores impact the extent and magnitude of host cell responsiveness, and this limits the capacity of pathogenic Yersinia spp. to fortify against attack by both early and late arms of the host innate immune response.

Place, publisher, year, edition, pages
London: Taylor & Francis Group, 2023
Keywords
Cytokine profiling, inflammasome, programmed cell death, anti-phagocytosis, translocon complexes, bacteria-eukaryotic cell contact
National Category
Microbiology in the medical area Microbiology
Research subject
Microbiology; Molecular Biology
Identifiers
urn:nbn:se:umu:diva-213952 (URN)10.1080/21505594.2023.2249790 (DOI)37621095 (PubMedID)2-s2.0-85168743016 (Scopus ID)
Funder
Swedish Research Council, 2014-2105Umeå UniversitySwedish Research Council, 2018-02676Swedish Research Council, 2022-04779Swedish Research Council, 2018-02914The Kempe Foundations
Available from: 2023-08-31 Created: 2023-08-31 Last updated: 2023-09-07Bibliographically approved
Toh, E., Baryalai, P., Nadeem, A., Aung, K. M., Chen, S., Persson, K., . . . Wai, S. N. (2022). Bacterial protein MakA causes suppression of tumour cell proliferation via inhibition of PIP5K1α/Akt signalling. Cell Death and Disease, 13(12), Article ID 1024.
Open this publication in new window or tab >>Bacterial protein MakA causes suppression of tumour cell proliferation via inhibition of PIP5K1α/Akt signalling
Show others...
2022 (English)In: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 13, no 12, article id 1024Article in journal (Refereed) Published
Abstract [en]

Recently, we demonstrated that a novel bacterial cytotoxin, the protein MakA which is released by Vibrio cholerae, is a virulence factor, causing killing of Caenorhabditis elegans when the worms are grazing on the bacteria. Studies with mammalian cell cultures in vitro indicated that MakA could affect eukaryotic cell signalling pathways involved in lipid biosynthesis. MakA treatment of colon cancer cells in vitro caused inhibition of growth and loss of cell viability. These findings prompted us to investigate possible signalling pathways that could be targets of the MakA-mediated inhibition of tumour cell proliferation. Initial in vivo studies with MakA producing V. cholerae and C. elegans suggested that the MakA protein might target the PIP5K1α phospholipid-signalling pathway in the worms. Intriguingly, MakA was then found to inhibit the PIP5K1α lipid-signalling pathway in cancer cells, resulting in a decrease in PIP5K1α and pAkt expression. Further analyses revealed that MakA inhibited cyclin-dependent kinase 1 (CDK1) and induced p27 expression, resulting in G2/M cell cycle arrest. Moreover, MakA induced downregulation of Ki67 and cyclin D1, which led to inhibition of cell proliferation. This is the first report about a bacterial protein that may target signalling involving the cancer cell lipid modulator PIP5K1α in colon cancer cells, implying an anti-cancer effect.

Place, publisher, year, edition, pages
Springer Nature, 2022
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-201753 (URN)10.1038/s41419-022-05480-7 (DOI)000895373300001 ()36473840 (PubMedID)2-s2.0-85143300255 (Scopus ID)
Funder
Swedish Research Council, 2018-02914Swedish Research Council, 2019-01720Swedish Research Council, 2019-01318Swedish Research Council, 2016-05009Swedish Cancer Society, CAN-2017-419Swedish Cancer Society, 2020-711Swedish Cancer Society, CAN-2017-381The Kempe Foundations, JCK-1728The Kempe Foundations, SMK-1553The Kempe Foundations, JCK2931.1U9Malmö University
Available from: 2022-12-21 Created: 2022-12-21 Last updated: 2023-09-05Bibliographically approved
Liu, Y., Nadeem, A., Sebastian, S., Olsson, M. A., Wai, S. N., Styring, E., . . . Raina, D. B. (2022). Bone mineral: A trojan horse for bone cancers. Efficient mitochondria targeted delivery and tumor eradication with nano hydroxyapatite containing doxorubicin. Materials Today Bio, 14, Article ID 100227.
Open this publication in new window or tab >>Bone mineral: A trojan horse for bone cancers. Efficient mitochondria targeted delivery and tumor eradication with nano hydroxyapatite containing doxorubicin
Show others...
2022 (English)In: Materials Today Bio, E-ISSN 2590-0064, Vol. 14, article id 100227Article in journal (Refereed) Published
Abstract [en]

Efficient systemic pharmacological treatment of solid tumors is hampered by inadequate tumor concentration of cytostatics necessitating development of smart local drug delivery systems. To overcome this, we demonstrate that doxorubicin (DOX), a cornerstone drug used for osteosarcoma treatment, shows reversible accretion to hydroxyapatite (HA) of both nano (nHA) and micro (mHA) size. nHA particles functionalized with DOX get engulfed in the lysosome of osteosarcoma cells where the acidic microenvironment causes a disruption of the binding between DOX and HA. The released DOX then accumulates in the mitochondria causing cell starvation, reduced migration and apoptosis. The HA+DOX delivery system was also tested in-vivo on osteosarcoma bearing mice. Locally delivered DOX via the HA particles had a stronger tumor eradication effect compared to the controls as seen by PET-CT and immunohistochemical staining of proliferation and apoptosis markers. These results indicate that in addition to systemic chemotherapy, an adjuvant nHA could be used as a carrier for intracellular delivery of DOX for prevention of tumor recurrence after surgical resection in an osteosarcoma. Furthermore, we demonstrate that nHA particles are pivotal in this approach but a combination of nHA with mHA could increase the safety associated with particulate nanomaterials while maintaining similar therapeutic potential.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Doxorubicin, Drug delivery, Nano and micro hydroxyapatite, Osteosarcoma, Solid tumor
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-193012 (URN)10.1016/j.mtbio.2022.100227 (DOI)000819915800003 ()2-s2.0-85125537714 (Scopus ID)
Available from: 2022-03-14 Created: 2022-03-14 Last updated: 2023-09-05Bibliographically approved
Kumar Gahlot, D., Wai, S. N., Erickson, D. L. & Francis, M. S. (2022). Cpx-signalling facilitates Hms-dependent biofilm formation by Yersinia pseudotuberculosis. npj Biofilms and Microbiomes, 8(1), Article ID 13.
Open this publication in new window or tab >>Cpx-signalling facilitates Hms-dependent biofilm formation by Yersinia pseudotuberculosis
2022 (English)In: npj Biofilms and Microbiomes, E-ISSN 2055-5008, Vol. 8, no 1, article id 13Article in journal (Refereed) Published
Abstract [en]

Bacteria often reside in sessile communities called biofilms, where they adhere to a variety of surfaces and exist as aggregates in aviscous polymeric matrix. Biofilms are resistant to antimicrobial treatments, and are a major contributor to the persistence and chronicity of many bacterial infections. Herein, we determined that the CpxA-CpxR two-component system influenced the ability of enteropathogenic Yersinia pseudotuberculosis to develop biofilms. Mutant bacteria that accumulated the active CpxR~P isoform failed to form biofilms on plastic or on the surface of the Caenorhabditis elegans nematode. A failure to form biofilms on the worm surface prompted their survival when grown on the lawns of Y. pseudotuberculosis. Exopolysaccharide production by the hms loci is the major driver of biofilms formed by Yersinia. We used a number of molecular genetic approaches to demonstrate that active CpxR~P binds directly to the promoter regulatory elements of the hms loci to activate the repressors of hms expression and to repress the activators of hms expression. Consequently, active Cpx-signalling culminated in a loss of exopolysaccharide production. Hence, the development of Y. pseudotuberculosis biofilms on multiple surfaces is controlled by the Cpx-signalling, and at least inpart this occurs through repressive effects on the Hms-dependent exopolysaccharide production.

Place, publisher, year, edition, pages
London: Nature Publishing Group, 2022
Keywords
Biofilms, Microbial genetics, Two-component system, CpxAR, Yersinia pseudotuberculosis, Caenorhabditis elegans
National Category
Microbiology Microbiology in the medical area
Research subject
Microbiology; molecular medicine (genetics and pathology); Biochemistry; Genetics; Molecular Biology
Identifiers
urn:nbn:se:umu:diva-193376 (URN)10.1038/s41522-022-00281-4 (DOI)000774860800001 ()35351893 (PubMedID)2-s2.0-85127231602 (Scopus ID)
Funder
Swedish Research Council, 2014-06652
Available from: 2022-03-29 Created: 2022-03-29 Last updated: 2023-09-05Bibliographically approved
Flodbring Larsson, P., Karlsson, R., Sarwar, M., Miftakhova, R. R., Wang, T., Khaja, A. S., . . . Persson, J. L. (2022). FcγRIIIa receptor interacts with androgen receptor and PIP5K1α to promote growth and metastasis of prostate cancer. Molecular Oncology
Open this publication in new window or tab >>FcγRIIIa receptor interacts with androgen receptor and PIP5K1α to promote growth and metastasis of prostate cancer
Show others...
2022 (English)In: Molecular Oncology, ISSN 1574-7891, E-ISSN 1878-0261Article in journal (Refereed) Published
Abstract [en]

Low-affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa) is a cell surface protein that belongs to a family of Fc receptors that facilitate the protective function of the immune system against pathogens. However, the role of FcγRIIIa in prostate cancer (PCa) progression remained unknown. In this study, we found that FcγRIIIa expression was present in PCa cells and its level was significantly higher in metastatic lesions than in primary tumors from the PCa cohort (P = 0.006). PCa patients with an elevated level of FcγRIIIa expression had poorer biochemical recurrence (BCR)-free survival compared with those with lower FcγRIIIa expression, suggesting that FcγRIIIa is of clinical importance in PCa. We demonstrated that overexpression of FcγRIIIa increased the proliferative ability of PCa cell line C4-2 cells, which was accompanied by the upregulation of androgen receptor (AR) and phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), which are the key players in controlling PCa progression. Conversely, targeted inhibition of FcγRIIIa via siRNA-mediated knockdown or using its inhibitory antibody suppressed growth of xenograft PC-3 and PC-3M prostate tumors and reduced distant metastasis in xenograft mouse models. We further showed that elevated expression of AR enhanced FcγRIIIa expression, whereas inhibition of AR activity using enzalutamide led to a significant downregulation of FcγRIIIa protein expression. Similarly, inhibition of PIP5K1α decreased FcγRIIIa expression in PCa cells. FcγRIIIa physically interacted with PIP5K1α and AR via formation of protein-protein complexes, suggesting that FcγRIIIa is functionally associated with AR and PIP5K1α in PCa cells. Our study identified FcγRIIIa as an important factor in promoting PCa growth and invasion. Further, the elevated activation of FcγRIII and AR and PIP5K1α pathways may cooperatively promote PCa growth and invasion. Thus, FcγRIIIa may serve as a potential new target for improved treatment of metastatic and castration-resistant PCa.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
AR pathway and antibody-based therapy, FcγRIIIa receptor, PIP5K1α, prostate cancer metastasis, targeted therapy
National Category
Cancer and Oncology
Research subject
Medicine; molecular medicine (genetics and pathology)
Identifiers
urn:nbn:se:umu:diva-192100 (URN)10.1002/1878-0261.13166 (DOI)000745727600001 ()34932854 (PubMedID)2-s2.0-85123504907 (Scopus ID)
Funder
Swedish Cancer Society, 2017-381Swedish Research Council, 2019-01318The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IG2013-5595The Kempe FoundationsCancerforskningsfonden i Norrland
Available from: 2022-02-01 Created: 2022-02-01 Last updated: 2024-03-20Bibliographically approved
Löwenmark, T., Li, X., Löfgren Burström, A., Zingmark, C., Ling, A., Kellgren, T. G., . . . Palmqvist, R. (2022). Parvimonas micra is associated with tumour immune profiles in molecular subtypes of colorectal cancer. Cancer Immunology and Immunotherapy, 71, 2565-2575
Open this publication in new window or tab >>Parvimonas micra is associated with tumour immune profiles in molecular subtypes of colorectal cancer
Show others...
2022 (English)In: Cancer Immunology and Immunotherapy, ISSN 0340-7004, E-ISSN 1432-0851, Vol. 71, p. 2565-2575Article in journal (Refereed) Published
Abstract [en]

The importance of the tumour microbiome in different aspects of colorectal cancer (CRC) has been increasingly recognised, but many questions remain. The aim of this study was to explore the effect of specific CRC associated microbes on the tumour immune response, which has a considerable prognostic value in CRC. We applied specific qPCR to detect Parvimonas micra and Fusobacterium nucleatum in tumour tissues from an immunologically well-characterised cohort of 69 CRC patients. This cohort included detailed analyses of immune profiles based on flow cytometry and transcriptomics in tumour tissue and blood, along with comprehensive analyses of molecular subtypes. P. micra and F. nucleatum were detected in 24% and 64% of tumour tissues, respectively. We found a significant association of P. micra with high-grade tumours and tumours of CMS1 subtype. F. nucleatum was significantly associated with right-sided tumours, microsatellite instability, and CMS1 tumours. The immunological analyses revealed significant associations of P. micra with activated CD69+ T lymphocytes and increased antigen-presenting HLA-DR+ B lymphocytes. P. micra was also positively associated with M1 and M2 macrophage traits. The impact of P. micra tumour colonisation on the immune response was further assessed using transcriptomics in validation of our findings. No associations were found between F. nucleatum and immune profiles in this study. Our findings support novel associations between P. micra and the immune response in CRC. A better understanding of these interactions might help to identify important predictive and prognostic tools as well as new targets for therapy.

Place, publisher, year, edition, pages
Springer, 2022
Keywords
Colorectal cancer, F. nucleatum, Immunity, Mucosal microbiota, P. micra
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-193335 (URN)10.1007/s00262-022-03179-4 (DOI)000770199300001 ()35301576 (PubMedID)2-s2.0-85126450770 (Scopus ID)
Funder
Cancerforskningsfonden i Norrland, AMP 21-1048Region Västerbotten, VLL-833541Swedish Cancer Society, 20 1271PjF
Available from: 2022-03-28 Created: 2022-03-28 Last updated: 2024-03-26Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-4793-4671

Search in DiVA

Show all publications