Abstract
The worldwide dispersion and sudden emergence of new antibiotic resistance genes (ARGs) determined the need in uncovering which environment participate most as their source and reservoir. ARGs closely related to those currently found in human pathogens occur in the resistome of anthropogenic impacted environments. However, the role of pristine environment as the origin and source of ARGs remains underexplored and controversy, particularly, the marine environments represented by the oceans. Here, due to the ocean nature, we hypothesized that the resistome of this pristine/low-impacted marine environment is represented by distant ARG homologs. To test this hypothesis we performed an in silico analysis on the Global Ocean Sampling (GOS) metagenomic project dataset focusing on the metallo-β-lactamases (MβLs) as the ARG model. MβLs have been a challenge to public health, since they hydrolyze the carbapenems, one of the last therapeutic choice in clinics. Using Hidden Markov Model (HMM) profiles, we were successful in identifying a high diversity of distant MβL homologs, related to the B1, B2, and B3 subclasses. The majority of them were distributed across the Atlantic, Indian, and Pacific Oceans being related to the chromosomally encoded MβL GOB present in Elizabethkingia genus. It was observed only a reduced number of metagenomic sequence homologs related to the acquired MβL enzymes (VIM, SPM-1, and AIM-1) that currently have impact in clinics. Therefore, low antibiotic impacted marine environment, as the ocean, are unlikely the source of ARGs that have been causing enormous threat to the public health.
Highlights
Antibiotic resistance genes (ARGs) represent a significant burden to public health and economies, since it directly affects the treatment and management of infectious diseases
Many of the antimicrobial compounds have been isolated from soil microorganisms and, in such niche, antibiotic producers and non-producers have developed self-protection mechanisms in response to the presence of these naturally produced antibiotics. These mechanisms have been evolving and fixing in such environmental microbiota, favoring the presence and maintenance of antibiotic resistance in soil environments (Nesme and Simonet, 2015). Aquatic environments, those under the influence of anthropogenic interventions, such as wastewater plants, hospital sewage and aquaculture farms, present a resistome mainly composed by ARGs identical or very similar to those found in clinics (Baquero et al, 2008; Figueira et al, 2011; Pruden et al, 2012; Tacão et al, 2012; Fróes et al, 2016)
Studies have demonstrated that the resistome of minimally impacted environments was composed by a higher proportion of distant homologs related to intrinsic and constitutive resistance determinants instead of horizontally acquired ARGs currently circulating in clinical pathogens (Storteboom et al, 2010; Chen et al, 2013; Hatosy and Martiny, 2015)
Summary
Antibiotic resistance genes (ARGs) represent a significant burden to public health and economies, since it directly affects the treatment and management of infectious diseases. We identified a high diversity of distant MβL homologs related to the three subclasses across 16/84 GOS marine sites, corresponding to superficial water (0.1–12 m) from coastal areas, open oceans, coral reef, coastal upwelling, abyssopelagic zone, mangrove and lake (Figure 1 and Table 1).
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