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- Davidsson, Sabina, 1972-, et al.
(författare)
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Cutibacterium acnes Induces the Expression of Immunosuppressive Genes in Macrophages and is Associated with an Increase of Regulatory T-Cells in Prostate Cancer
- 2021
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Tumors and infectious agents both benefit from an immunosuppressive environment. Cutibacterium acnes (C. acnes) is a bacterium in the normal skin microbiota, which has the ability to survive intracellularly in macrophages and is significantly more common in prostate cancer tissue compared with normal prostate tissue. This study investigated if prostate cancer tissue culture positive for C. acnes has a higher infiltration of regulatory T-cells (Tregs) and if macrophages stimulated with C. acnes induced the expression of immunosuppressive genes that could be linked to an increase of Tregs in prostate cancer. Real-time PCR and enzyme-linked immunosorbent spot assay (ELISA) were used to examine the expression of immunosuppressive genes in human macrophages stimulated in vitro with C. acnes, and associations between the presence of C. acnes and infiltration of Tregs were investigated by statistically analyzing data generated in two previous studies. The in vitro results demonstrated that macrophages stimulated with C. acnes significantly increased their expression of PD-L1, CCL17, and CCL18 mRNA and protein (p ,0.05). In the cohort, Tregs in tumor stroma and tumor epithelia were positively associated with the presence of C. acnes (P = 0.0004 and P = 0.046, respectively). Since the macrophages stimulated with C. acnes in vitro increased the expression of immunosuppressive genes, and prostate cancer patients with prostatic C. acnes infection had higher infiltration of Tregs than their noninfected counterparts, we suggest that C. acnes may contribute to an immunosuppressive tumor environment that is vital for prostate cancer progression.
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| 3. |
- Bengtsson, Torbjörn, 1955-, et al.
(författare)
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Plantaricin NC8 αβ exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The use of conventional antibiotics has substantial clinical efficacy, however these vital antimicrobial agents are becoming less effective due to the dramatic increase in antibiotic-resistant bacteria. Novel approaches to combat bacterial infections are urgently needed and bacteriocins represent a promising alternative. In this study, the activities of the two-peptide bacteriocin PLNC8 αβ were investigated against different Staphylococcus spp. The peptide sequences of PLNC8 α and β were modified, either through truncation or replacement of all L-amino acids with D-amino acids. Both L- and D-PLNC8 αβ caused rapid disruption of lipid membrane integrity and were effective against both susceptible and antibiotic resistant strains. The D-enantiomer was stable against proteolytic degradation by trypsin compared to the L-enantiomer. Of the truncated peptides, β1-22, β7-34 and β1-20 retained an inhibitory activity. The peptides diffused rapidly (2 min) through the bacterial cell wall and permeabilized the cell membrane, causing swelling with a disorganized peptidoglycan layer. Interestingly, sub-MIC concentrations of PLNC8 αβ substantially enhanced the effects of different antibiotics in an additive or synergistic manner. This study shows that PLNC8 αβ is active against Staphylococcus spp. and may be developed as adjuvant in combination therapy to potentiate the effects of antibiotics and reduce their overall use.
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| 6. |
- Sagerfors, Susanna, 1977-, et al.
(författare)
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Clinical and genomic features of Corynebacterium macginleyi-associated infectious keratitis
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Infectious keratitis is a potentially sight threatening ophthalmological emergency. Contact lens wear is a common risk factor. Diagnostic advances such as MALDI-TOF MS provides new insights into the spectrum of corneal pathogens and on microbes previously considered as commensals. Corynebacterium macginleyi was described in 1995, and in 2018, the genomic features of three isolates were reported after whole-genome sequencing. Here we describe the clinical characteristics of patients with infectious keratitis (n = 29) presumably caused by Corynebacterium macginleyi, and analyze the genomic features of C. macginleyi (n = 22) isolated from the corneal ulcers of these patients. The disease course was uneventful apart from minor interventions such as corneal cross-linking and amniotic membrane transplant. Genome sequencing and comparison revealed a highly conserved core genome of C. macginleyi. Based on the analyses of single nucleotide polymorphisms, the population could be divided into two main clades that also differed in a few clade-specific genomic islands. Patients infected with an isolate belonging to the minor clade (n = 7) presented a more severe disease. Comparisons with other corynebacterial species clearly separated C. macginleyi. C. macginleyi may be considered a corneal pathogen; genomic analysis provided insights into its population structure and disease-causing potential.
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| 7. |
- Sagerfors, Susanna, 1977-, et al.
(författare)
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Corneal Culture in Infectious Keratitis : Effect of the Inoculation Method and Media on the Corneal Culture Outcome
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To compare two different methods of corneal culture in infectious keratitis: multiple sampling for direct inoculation and enrichment (standard method) and a single sample via transport medium for indirect inoculation (indirect inoculation method).METHODS: Prospective inclusion of patients fulfilling predefined criteria of infectious keratitis undergoing corneal culture according to both studied methods in a randomized order.RESULTS: = 0.002) and a significantly higher proportion of microorganisms than the indirect inoculation method, with a Cohen's kappa of 0.38 (95% CI: 0.28-0.49) for agreement between the methods. Subanalysis of culture results showed that direct inoculation on gonococcal agar only combined with the indirect inoculation method resulted in a similar rate of culture positive patients and proportion of detected microorganisms to the standard method.CONCLUSION: Indirect inoculation of one corneal sample cannot replace direct inoculation of multiple corneal samples without loss of information. A combination of directly and indirectly inoculated samples can reduce the number of corneal samples by four without statistically significant differences in culture outcome or in the proportion of detected microorganisms.
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| 8. |
- Sagerfors, Susanna, 1977-, et al.
(författare)
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Does the sampling instrument influence corneal culture outcome in patients with infectious keratitis? A retrospective study comparing cotton tipped applicator with knife blade
- 2020
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Ingår i: BMJ Open Ophthalmology. - : BMJ Publishing Group Ltd. - 2397-3269. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to compare the efficacy of a cotton tipped applicator and a knife blade in obtaining corneal samples in patients with infectious keratitis.Methods and analysis: This is a retrospective cohort study of patients with suspected infectious keratitis during 2004-2014. Samples for corneal culture were obtained by a cotton tipped applicator and a knife blade, and directly inoculated on GC agar, blood agar and Sabouraud agar.Results: In all, 355 patients were included. Corneal sampling by cotton tipped applicator yielded a significantly higher rate of patients with positive corneal culture, 156/355 (43.9%), compared with knife blade, 111/355 (31.3%) (p<0.001). On a patient level, the culture results obtained by the cotton tipped applicator and the knife blade were identical in 269/355 (76%) of the patients. The overall agreement between the two instruments on microbial level was 0.66 (Cohen's kappa 95% CI 0.60 to 0.72).Conclusion: Corneal sampling by cotton tipped applicator generated a higher rate of positive corneal cultures and a higher proportion of isolated microbes than by knife blade. Future studies with randomised sampling order are needed to establish which instrument, cotton tipped applicator or knife blade, is the most effective in sampling microbes for direct inoculation in patients with infectious keratitis.
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| 9. |
- Sagerfors, Susanna, et al.
(författare)
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In the eye of the ophthalmologist : the corneal microbiome in microbial keratitis
- 2024
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Ingår i: Graefe's Archives for Clinical and Experimental Ophthalmology. - : Springer. - 0721-832X .- 1435-702X. ; 262:5, s. 1579-1589
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To describe the bacterial findings by a targeted sequencing approach from corneal samples of patients with microbial keratitis and factors influencing culture outcome of indirectly inoculated corneal specimen.METHODS: Prospective inclusion of patients fulfilling predefined criteria of microbial keratitis. Samples from the corneal lesion were collected and dispensed in liquid transport medium, from which both culture and targeted amplification and sequencing of the V3-V4 region of the 16S rRNA gene were carried out. Additional standard corneal culture from the corneal lesions was also performed. Factors influencing culture outcome of indirectly inoculated corneal samples were identified by a multivariate regression model incorporating quantitative data from sequencing.RESULTS: Among the 94 included patients with microbial keratitis, contact lens wear (n = 69; 73%) was the most common risk factor. Contact lens wearers displayed significant differences in the bacterial community composition of the corneal lesion compared to no lens wearers, with higher abundance of Staphylococcus spp., Corynebacterium spp., and Stenotrophomonas maltophilia. Targeted sequencing detected a potential corneal pathogen in the highest proportional abundance among 9 of the 24 (38%) culture-negative patients with microbial keratitis. Age, bacterial density in the sample, and prior antibiotic treatment significantly influenced culture outcome of indirectly inoculated corneal samples.CONCLUSION: Targeted sequencing may provide insights on pathogens in both culture negative episodes of microbial keratitis and among subgroups of patients with microbial keratitis as well as factors influencing culture outcome of indirectly inoculated corneal samples.
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