Department of Microbiology and Immunology
http://hdl.handle.net/20.500.12283/331
2024-03-28T12:40:23ZWhole genome sequences of multi-drug resistant Escherichia coli isolated in a Pastoralist Community of Western Uganda :
http://hdl.handle.net/20.500.12283/764
Whole genome sequences of multi-drug resistant Escherichia coli isolated in a Pastoralist Community of Western Uganda :
Iramiot, Jacob Stanley; Kajumbula, Henry; Bazira, Joel; Villiers, Etienne P. de; Asiimwe, Benon B.
Background
The crisis of antimicrobial resistance is already here with us, affecting both humans and animals alike and very soon, small cuts and surgeries will become life threatening. This study aimed at determine the whole genome sequences of multi-drug resistant Escherichia coli isolated in a Pastoralist Community of Western Uganda: phylogenomic changes, virulence and resistant genes.
Methods
This was a laboratory based cross sectional study. Bacterial isolates analyzed in this study were 42 multidrug resistant E. coli isolated from stool samples from both humans (n = 30) and cattle (n = 12) in pastoralist communities collected between January 2018-March 2019. Most of the isolates (41/42) were resistant to three or more antibiotics (multi-drug resistant) and 21/42 isolates were ESBL producers; 13/30 from human and 8/12 from cattle. Whole Genome Sequencing (WGS) was carried out at the facilities of Kenya Medical Research Institute-Wellcome trust, Kilifi, to determine the phylogenomic changes, virulence and resistant genes.
At household level, the genomes from both human and animals clustered away from one another except for one instance where two human isolates from the same household clustered together. However, 67% of the E. coli isolated from cattle were closely related to those phylogroup B1. The carriage of multiple AMR genes was higher from the E. coli population from humans than those from cattle. Among these were Beta-lactamase; blaOXA-1: Class D beta-lactamases; blaTEM-1, blaTEM-235: Beta-lactamase; catA1: chloramphenicol acetyl transferase; cmlA1: chloramphenicol efflux transporter; dfrA1, dfrA12, dfrA14, dfrA15, dfrA17, dfrA5, dfrA7, dfrA8: macrolide phosphotransferase; oqxB11: RND efflux pump conferring resistance to fluoroquinolone; qacL, qacEdelta1: quinolone efflux pump; qnrS1: quinolone resistance gene; sul1, sul2, sul3: sulfonamide resistant; tet(A), tet(B): tetracycline efflux pump. A high variation of virulence genes was registered among the E. coli genomes from humans than those of cattle origin.
Conclusion
From the analysis of the core genome and phenotypic resistance, this study has demonstrated that the E. coli of human origin and those of cattle origin may have a common ancestry. Limited sharing of virulence genes presents a challenge to the notion that AMR in humans is as a result of antibiotic use in the farm and distorts the picture of the directionality of transmission of AMR at a human-animal interface and presents a task of exploring alternative routes of transmission of AMR.
Article
2020-05-29T00:00:00ZAnnona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through regulation of CASP9 and the CXCL1/CXCR2 genes axis.
http://hdl.handle.net/20.500.12283/760
Annona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through regulation of CASP9 and the CXCL1/CXCR2 genes axis.
Gavamukulya, Yahaya; Maina, Esther N.; El-Shemy, Hany A.; Merokac, Amos M.; Kangogo, Geoffrey K.; Magoma, Gabriel; Wamunyokoli, Fred
BACKGROUND: Green synthesized nanoparticles have been earmarked for use in nanomedicine including for the development of better anticancer drugs.
OBJECTIVE: The aim of this study was to undertake biochemical evaluation of anticancer activities of green synthesized silver nanoparticles (AgNPs) from ethanolic extracts of fruits (AgNPs-F) and leaves (AgNPs-L) of Annona muricata. METHODS: Previously synthesized silver nanoparticles were used for the study. The effects of the AgNPs and 5-Fluorouracil were studied on PC3, HeLa and PNT1A cells. The resazurin, migration and colonogenic assays as well as qRT-PCR were employed.
RESULTS: The AgNPs-F displayed significant antiproliferative effects against HeLa cells with an IC50 of 38.58 g/ml and PC3 cells with an IC50 of 48.17 g/ml but selectively spared normal PNT1A cells (selectivity index of 7.8), in comparison with first line drug 5FU and AgNPs-L whose selectivity index were 3.56 and 2.26 respectively. The migration assay revealed potential inhibition of the metastatic activity of the cells by the AgNPs-F while the colonogenic assay indicated the permanent effect of the AgNPs-F on the cancer cells yet being reversible on the normal cells in contrast with 5FU and AgNPs-L. CASP9 was significantly over expressed in all HeLa cells treated with the AgNPs-F (1.53-fold), AgNPs-L (1.52-fold) and 5FU (4.30-fold). CXCL1 was under expressed in HeLa cells treated with AgNPs-F (0.69-fold) and AgNPs-L (0.58-fold) and over expressed in cells treated with 5FU (4.95-fold), but the difference was not statistically significant. CXCR2 was significantly over expressed in HeLa cells treated with 5FU (8.66-fold) and AgNPs-F (1.12-fold) but under expressed in cells treated with AgNPs-L (0.76-fold).
CONCLUSIONS: Here we show that biosynthesized AgNPs especially AgNPs-F can be used in the development of novel and better anticancer drugs. The mechanism of action of the AgNPs involves activation of the intrinsic apoptosis pathway through upregulation of CASP9 and concerted down regulation of the CXCL1/ CXCR2 gene axis.
Keywords: Silver nanoparticles, HeLa, PC3, PNT1A, CASP9, CXCL1/CXCR2
Article
2021-02-06T00:00:00ZPrevalence and dynamics of clinically significant bacterial contaminants in herbal medicines sold in East Africa from 2000 to 2020: a systematic review and meta-analysis.
http://hdl.handle.net/20.500.12283/734
Prevalence and dynamics of clinically significant bacterial contaminants in herbal medicines sold in East Africa from 2000 to 2020: a systematic review and meta-analysis.
Walusansa, Abdul; Asiimwe, Savina; Kafeero, Hussein. M.; Iramiot, J. Stanley; Ssenku, Jamilu. E.; Nakavuma, Jesca. L.; Kakudidi, Esezah. K.
Background: Infectious diseases remain a leading cause of mortality and morbidity around the world, and those caused by bacteria are common in the East African region. In this region, trade and consumption of herbal medicine has been expanding in the recent decades. Herbal medicines may be contaminated with pathogenic bacteria; however, there is limited information due to fragmented studies in East Africa. In this meta-analysis, we critically analyzed original research related to the incidence of pathogenic bacterial contaminants of HM in the East African region since 2000. The aim was to create a comprehensive understanding of the extent and dynamics of bacterial contamination in HM, to guide future research and concerted public health protection in the region.
Methodology: The study was conducted according to the standards of the Preferred Reporting Items for Systematic Reviews and Meta-analyses. We searched and evaluated published articles from eleven electronic databases (Google Scholar, PubMed, HerbMed, MEDLINE, Science Direct, Scifinder Scholar, Cochrane Library, International Pharmaceutical Abstracts, EMBASE, Biological Abstracts and Commonwealth Agricultural Bureau
Abstracts). Prevalences of different bacterial species, Cochran’s Q test, and the I2 statistic for heterogeneity were evaluated using a software called MedCalcs. Random and fixed effects models were used to determine the pooled prevalence of clinically significant bacteria from studies which were included in this meta-analysis. The potential sources of heterogeneity were examined through sensitivity analysis, sub-group analysis, and meta-regression at 95% level of significance.
Results: Fourteen studies met our inclusion criteria. Overall, the studies were highly heterogeneous (I2 = 98.48%) and there was no evidence of publication bias. Escherichia coli was the most prevalent contaminant. Salmonella spp. and Shigella spp. were the most frequently reported primary pathogens with pooled prevalence of 10.4% and 6.3%, respectively. Our findings are in tandem with recent systematic reviews conducted in Europe and Asia, but are in discrepancy with the reviews recently conducted in southern Africa.
Conclusion and recommendations: The East African herbal medicine industry poses considerable health risks to communities through dissemination of clinically significant bacteria. Presence of enteric bacterial contaminants indicates possible fecal pollution of herbal medicine region-wide. Adequate research pertaining to microbial safety of herbal medicine in the East African countries remains highly desired. The latter will enable establishment of strong, region-wide herbal safety mechanisms in order to support comprehensive public health protection in East Africa.
Keywords: Bacterial contamination, Herbal medicine, East Africa, Systematic review
Article
2021-01-01T00:00:00ZAntimicrobial resistance at the human–animal interface in the pastoralist communities of Kasese District, South Western Uganda.
http://hdl.handle.net/20.500.12283/684
Antimicrobial resistance at the human–animal interface in the pastoralist communities of Kasese District, South Western Uganda.
Iramiot, Jacob Stanley; Kajumbula, Henry; Bazira, Joel; Kansiime, Catherine; Asiimwe, Benon B.
Intensive usage of antimicrobials in the management of animal diseases leads to selection for resistance among microorganisms. this study aimed to assess antimicrobial use and to describe factors associated with the transmission of antimicrobial resistance between humans and animals in pastoralist communities of Kasese district. A mixed-methods approach was employed in this study. Rectal swabs were collected from the participants and cattle and transported in carry–Blaire transport medium to the laboratory within 24 h of collection for culture and sensitivity to confirm carriage of multi-drug resistant bacteria. In-depth interviews were conducted among veterinary officers, veterinary drug vendors, human health facility in-charges in both public and private health facilities, and operators of human pharmacies and drug shops. carriage of multi-drug resistant bacteria among humans was 88 (93%) and 76(80%) among cattle. Consumption of lakeshore water and carriage of multi-drug resistant bacteria in cattle were associated with carriage of multi-drug resistant bacteria in the human population. the prevalence of multi-drug resistance among organisms isolated from both humans and animals was high. There is a high likelihood of transmission of multi-drug resistance between humans and animals.
Article
2020-01-01T00:00:00Z