Pathogens, Virulence and Resistance Genes Surveillance with Metagenomics Can Pre-empt Dissemination and Escalation of Untreatable Infections: A Systematic Review and Meta-analyses

Abstract

AbstractBackgroundThe dissemination of pathogens carrying genetic elements such as antimicrobial resistance genes (ARGs), mobile-genetic elements (MGEs), virulome and methylome have a negative impact on food and environment safety, water quality and animal and human health. The applications of metagenomics to monitor and identify the prevalence/endemicity and emergence of these pathogenic agents from different sources were examined.MethodsArticles published in English language up to October 2020 were searched for on PubMed. Qualitative and quantitative data extracted from the included articles were translated into charts and maps. GraphPad Prism 9.0.2 was used to undertake statistical analysis using descriptive and column statistics, Chi-square, ANOVA, Wilcoxon’s signed-rank, and one-sample t-test.ResultsIn all, 143 articles from 39 countries from Europe, America, Asia, and Africa were quantitatively analysed. Metagenomes from sewage/wastewater, surface water samples (ocean, sea, river lake, stream and tap water), WWTP, effluents and sludge samples contained pathogenic bacteria (Aeromonas, Acinetobacter, Pseudomonas, Streptococcus, Bacteroides, Escherichia coli, Salmonella enterica, Klebsiella pneumoniae and Acinetobacter baumannii), viruses (Adenovirus, Enterovirus, Hepatovirus, Mamastrovirus and Rotavirus) and parasites (Acanthamoeba, Giardia, Entamoeba, Blastocystis and Naegleria). Integrons, plasmids, transposons, insertion sequences, prophages and integrative and conjugative elements were identified. ARGs mediating resistance to important antibiotics, including β-lactams, aminoglycosides, fluoroquinolones, and tetracycline, and virulence factors such as secretion system, adherence, antiphagocytosis, capsule, invasion, iron uptake, hemolysin, and flagella.ConclusionClinically important pathogens, ARGs, and MGEs were identified in diverse clinical, environmental, and animal sources through metagenomics, which can be used to determine the prevalence and emergence of known and unknown pathogens and ARGs.Importance/significanceGlobal metagenomic analyses of drinking water, effluents, influents, un/-treated sewage, WWTPs, sludge, rivers, lakes, soil, sediments, biosolid, air and plants. showed the global distribution of diverse clinically important ARGs on mobile genetic elements, antimicrobial-resistant bacteria (ARB) and pathogens, metal resistance genes, and virulence genes in almost all environments. These depict the importance of shot-gun metagenomics as a surveillance tool for AMR and infectious disease control to safeguard water & food quality as well as public health from water- and food-borne outbreaks of pathogenic and ARB infections. More concerning was the identification of ARGs to last-resort antibiotics i.e., carbapenems, colistin, & tigecycline.