A review of phage mediated antibacterial applications

Background: For over a decade, resistance to newly synthesized antibiotics has been observed worldwide. The challenge of antibiotic resistance has led to several pharmaceutical companies to abandon the synthesis of new drugs in fear of bacteria developing resistance in a short period hence limiting initial investment return. To this effect, alternative approaches such as the use of bacteriophages to treat bacterial infections are being explored. This review explores the recent advances in phage-mediated antibacterial applications and their limitations.Methods: We conducted a comprehensive literature search of PubMed, Lib Hub and Google Scholar databases from January 2019 to November 2019. The search key words used were the application of bacteriophages to inhibit bacterial growth and human phage therapy to extract full-text research articles and proceedings from International Conferences published only in English.Results: The search generated 709 articles of which 95 full-text research articles fulfilled the inclusion guidelines. Transmission Electron Microscopy morphological characterization conducted in 23 studies registered Myoviruses, Siphoviruses, Podoviruses, and Cytoviruses phage families while molecular characterization revealed that some phages were not safe to use as they harbored undesirable genes. All in vivo phage therapy studies in humans and model animals against multidrug-resistant (MDR) bacterial infection provided 100% protection. Ex vivo and in vitro phage therapy experiments exhibited overwhelming results as they registered high efficacies of up to 100% against MDR clinical isolates. Phage-mediated bio-preservation of foods and beverages and bio-sanitization of surfaces were highly successful with bacterial growth suppression of up to 100%. Phage endolysins revealed efficacies statistically comparable to those of phages and restored normal ethanol production by completely eradicating lactic acid bacteria in ethanol fermenters. Furthermore, the average multiplicity of infection was highest in ex vivo phage therapy (557,291.8) followed by in vivo (155,612.4) and in vitro (434.5)

Whole genome analysis of selected human and animal rotaviruses identified in Uganda from 2012 to 2014 reveals complex genome reassortment events between human, bovine, caprine and porcine strains

Rotaviruses of species A (RVA) are a common cause of diarrhoea in children and the young of various other mammals and birds worldwide. To investigate possible interspecies transmission of RVAs, whole genomes of 18 human and 6 domestic animal RVA strains identified in Uganda between 2012 and 2014 were sequenced using the Illumina HiSeq platform. The backbone of the human RVA strains had either a Wa- or a DS-1-like genetic constellation. One human strain was a Wa-like mono-reassortant containing a DS-1-like VP2 gene of possible animal origin. All eleven genes of one bovine RVA strain were closely related to those of human RVAs. One caprine strain had a mixed genotype backbone, suggesting that it emerged from multiple reassortment events involving different host species. The porcine RVA strains had mixed genotype backbones with possible multiple reassortant events with strains of human and bovine origin.Overall, whole genome characterisation of rotaviruses found in domestic animals in Uganda strongly suggested the presence of human-to animal RVA transmission, with concomitant circulation of multi-reassortant strains potentially derived from complex interspecies transmission events. However, whole genome data from the human RVA strains causing moderate and severe diarrhoea in under-fives in Uganda indicated that they were primarily transmitted from person-to-person

Genotypic characterisation of Avian paramyxovirus type-1 viruses isolated from aquatic birds in Uganda

Avian paramyxovirus type-1 (APMV-1) viruses of the lentogenic pathotypes are often isolated from wild aquatic birds and may mutate to high pathogenicity when they cross into poultry and cause debilitating Newcastle disease. This study characterised AMPV-1 isolated from fresh faecal droppings from wild aquatic birds roosting sites in Uganda. Fresh faecal samples from wild aquatic birds at several waterbodies in Uganda were collected and inoculated into 9–10-day-old embryonated chicken eggs. After isolation, the viruses were confirmed as APMV-1 by APMV-1-specific polymerase chain reaction (PCR). The cleavage site of the fusion protein gene for 24 representative isolates was sequenced and phylogenetically analysed and compared with representative isolates of the different APMV-1 genotypes in the GenBank database. In total, 711 samples were collected from different regions in the country from which 72 isolates were recovered, giving a prevalence of 10.1%. Sequence analysis of 24 isolates revealed that the isolates were all lentogenic, with the typical 111GGRQGR’L117 avirulent motif. Twenty-two isolates had similar amino acid sequences at the cleavage site, which were different from the LaSota vaccine strain by a silent nucleotide substitution T357C. Two isolates, NDV/waterfowl/Uganda/MU150/2011 and NDV/waterfowl/Uganda/MU186/2011, were different from the rest of the isolates in a single amino acid, with aspartate and alanine at positions 124 and 129, respectively. The results of this study revealed that Ugandan aquatic birds indeed harbour APMV-1 that clustered with class II genotype II strains and had limited genetic diversity

Growing Problem of Multidrug-Resistant Enteric Pathogens in Africa

A disproportionate number of low-income persons are affected

Co-Surveillance of Rotaviruses in Humans and Domestic Animals in Central Uganda Reveals Circulation of Wide Genotype Diversity in the Animals

Rotavirus genotypes are species specific. However, interspecies transmission is reported to result in the emergence of new genotypes. A cross-sectional study of 242 households with 281 cattle, 418 goats, 438 pigs, and 258 humans in Uganda was undertaken between 2013 and 2014. The study aimed to determine the prevalence and genotypes of rotaviruses across co-habiting host species, as well as potential cross-species transmission. Rotavirus infection in humans and animals was determined using NSP3 targeted RT-PCR and ProSpecT Rotavirus ELISA tests, respectively. Genotyping of rotavirus-positive samples was by G- and P-genotype specific primers in nested RT-PCR assays while genotyping of VP4 and VP7 proteins for the non-typeable human positive sample was done by Sanger sequencing. Mixed effect logistic regression was used to determine the factors associated with rotavirus infection in animals. The prevalence of rotavirus was 4.1% (95% CI: 3.0-5.5%) among the domestic animals and 0.8% (95% CI: 0.4-1.5%) in humans. The genotypes in human samples were G9P[8] and P[4]. In animals, six G-genotypes, G3(2.5%), G8(10%), G9(10%), G11(26.8%), G10(35%), and G12(42.5%), and nine P-genotypes, P[1](2.4%), P[4](4.9%), P[5](7.3%), P[6](14.6%), P[7](7.3%), P[8](9.8%), P[9](9.8%), P[10](12.2%), and P[11](17.1%), were identified. Animals aged 2 to 18 months were less likely to have rotavirus infection in comparison with animals below 2 months of age. No inter-host species transmission was identified

Current Advances on Virus Discovery and Diagnostic Role of Viral Metagenomics in Aquatic Organisms

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Occurrence and antibiotic susceptibility of fish bacteria isolated from Oreochromis niloticus (Nile tilapia) and Clarias gariepinus (African catfish) in Uganda.

The intention of this study was to identify the bacterial pathogens infecting Oreochromis niloticus (Nile tilapia) and Clarias gariepinus (African catfish), and to establish the antibiotic susceptibility of fish bacteria in Uganda. A total of 288 fish samples from 40 fish farms (ponds, cages, and tanks) and 8 wild water sites were aseptically collected and bacteria isolated from the head kidney, liver, brain and spleen. The isolates were identified by their morphological characteristics, conventOccurrence and antibiotic susceptibility of fish bacteria isolated from Oreochromis niloticus (Nile tilapia) and Clarias gariepinus (African catfish) in Uganda.publishedVersio