Biology subjects

Geluk, A.

Publications and source records attributed to Geluk, A..

3 recordsLinked to original sources

bioRxiv2024

Proteomic And Transcriptomic Host Biomarkers For Detection Of Pleural Tuberculosis

Current diagnosis of pleural tuberculosis (PLTB) is based on highly invasive procedures. Therefore, blood-based host biomarkers could represent a low-invasive diagnostic alternative. Plasma and pleural effusion, as well as blood-and pleural fluid mononuclear cells (PBMCs and PFMCs), were sampled from patients with PLTB and other pleural diseases (OPLDs). In pleural effusion, ApoA1, C1q, CRP, IL-6, IFN-{gamma}, IP-10, MIG, S100A12, SAA1/A2, and serpin-A3 were significantly higher in PLTB compared to OPLD, whereas only SAA1/A2 showed discriminatory potential in plasma. Increased mRNA levels were observed in PFMCs of PLTB for CD8A, GBP5, SLAMF7, CXCL10, IL2, GNLY, IL23A, PDCD1 and BCMA, whereas HMOX1, CD163, DUSP3, IGF1, GUSB and MARCO were decreased. In PBMCs of PLTB, only CCL22 expression was decreased. GBP5 was significantly higher expressed in PLTB for both cell types. This study shows the potential of transcriptomic and proteomic host biomarkers to differentiate PLTB from OPLDs also when applying low-invasive methods.

microbiology↗

bioRxiv2022

Mycobacterium leprae and host immune transcriptomic signatures for reactional states in leprosy

BackgroundMycobacterium leprae transcriptomic and human host immune gene expression signatures that demonstrate a plausible association with type I (T1R) and type II reactions (T2R) aid in early diagnosis, prevention of nerve damage and consequent demyelinating neuropathy in leprosy. The aim of the study is to identify M. leprae and host-associated gene-expression signatures that are associated with reactional states in leprosy. MethodsThe differentially expressed genes from the whole transcriptome of M. leprae were determined using genome-wide hybridization arrays with RNA extracted from skin biopsies of 20 T1R, 20 T2R and 20 non reactional controls (NR). Additionally, human immune gene-expressions were profiled using RT2-PCR profiler arrays and real-time qPCRs. ResultsThe RNA quality was optimal in 16 NR, 18 T1R and 19 T2R samples. Whole transcriptome expression array of these samples revealed significant overexpression of the genes that encode integral and intrinsic membrane proteins, hydrolases and oxidoreductases. In T1R lesional skin biopsy specimens, the top 10 over significantly upregulated genes are ML2064, ML1271, ML1960, ML122, ML2498, ML1996, ML2388, ML0429, ML2030 and ML0224 in comparison to NR. In T2R, genes ML2498, ML1526, ML0394, ML1960, ML2388, ML0429, ML0281, ML1847, ML1618 and ML1271 were significantly upregulated. We noted ML2664 was significantly upregulated in T1R and repressed in T2R. Conversely, we havent noted any genes upregulated in T2R and repressed in T1R. In both T1R and T2R, ML2388 was significantly overexpressed. This gene encodes a probable membrane protein and epitope prediction using Bepipred -2.0 revealed a distinct B-cell epitope. Overexpression of ML2388 was noted consistently across the reaction samples. From the host immune gene expression profiles, genes for CXCL9, CXCL2, CD40LG, IL17A and CXCL11 were upregulated in T1R when compared to the NR. In T2R, CXCL10, CXCL11, CXCL9, CXCL2 and CD40LG were upregulated. ConclusionA gene set signature involving bacterial genes ML2388, ML2664, and host immune genes CXCL10 and IL-17A can be transcriptomic markers for reactional states in leprosy.

molecular biology↗

bioRxiv2018

Detection of Mycobacterium leprae DNA in soil; Multiple needles in the haystack?

BackgroundLeprosy is an infectious disease caused by Mycobacterium leprae and Mycobacterium lepromatosis affecting the skin and nerves. Despite decades of availability of adequate treatment, transmission is unabated and routes of transmission are not completely understood. Notwithstanding the general assumption that untreated M. leprae infected humans represent the major source of transmission, scarce reports indicate that environmental specimens could play a role as a reservoir as well.\n\nMethodologyIn order to identify patterns of bacterial transmission, this study investigated whether M. leprae DNA is present in soil of regions where leprosy is endemic or areas with possible animal reservoirs (armadillos and red squirrels). Soil samples were collected in Bangladesh, Suriname and the British Isles. The presence of M. leprae DNA was determined by RLEP PCR and M. leprae SNP types were further identified by Sanger sequencing of loci 1-3.\n\nResultsM. leprae DNA was identified in soil samples from environments inhabited by leprosy patients (Bangladesh), armadillos (Suriname) and the lepromatous Eurasian red squirrels (British Isles). In Bangladesh SNP type 1 was detected, Suriname soil contained SNP type 1 or 2, whilst SNP typing was not feasible for the British samples.\n\nConclusionsIt is conceivable that, besides humans and animals, environmental reservoirs may play a role in transmission. Frequent, intense contact with multibacillary leprosy patients poses the highest risk of transmission, and even though the risk of environmental contamination is low, it may offer a possible explanation for the occurrence of leprosy in individuals in areas without any reported human leprosy.

microbiology↗