scholarly journals A resistome roadmap: from the human body to pristine environments

2021 ◽  
Author(s):  
Lucia Maestre-Carballa ◽  
Manuel Martínez-García ◽  
Vicente Navarro-López

A comprehensive characterization of the human body resistome (sets of antibiotic resistance genes (ARGs)) is yet to be done and paramount for addressing the antibiotic microbial resistance threat. Here, we study the resistome of 771 samples from five major body parts (skin, nares, vagina, gut and oral cavity) of healthy subjects from the Human Microbiome Project and addressed the potential dispersion of ARGs in pristine environments. A total of 28,731 ARGs belonging to 344 different ARG types were found in the HMP proteome dataset (n=9.1x107 proteins analyzed). Our study reveals a distinct resistome profile (ARG type and abundance) between body sites and high inter-individual variability. Nares had the highest ARG load (≈5.4 genes/genome) followed by the oral cavity, while the gut showed one of the highest ARG richness (shared with nares) but the lowest abundance (≈1.3 genes/genome). Fluroquinolone resistance genes were the most abundant in the human body, followed by macrolide-lincosamide-streptogramin (MLS) or tetracycline. Most of the ARGs belonged to common bacterial commensals and multidrug resistance trait was predominant in the nares and vagina. Our data also provide hope, since the spread of common ARG from the human body to pristine environments (n=271 samples; 77 Gb of sequencing data and 2.1x108 proteins analyzed) thus far remains very unlikely (only one case found in an autochthonous bacterium from a pristine environment). These findings broaden our understanding of ARG in the context of the human microbiome and the One-Health Initiative of WHO uniting human host-microbes and environments as a whole.

2021 ◽  
Vol 22 (13) ◽  
pp. 6891
Author(s):  
João S. Rebelo ◽  
Célia P. F. Domingues ◽  
Francisco Dionisio ◽  
Manuel C. Gomes ◽  
Ana Botelho ◽  
...  

Recently, much attention has been paid to the COVID-19 pandemic. Yet bacterial resistance to antibiotics remains a serious and unresolved public health problem that kills hundreds of thousands of people annually, being an insidious and silent pandemic. To contain the spreading of the SARS-CoV-2 virus, populations confined and tightened hygiene measures. We performed this study with computer simulations and by using mobility data of mobile phones from Google in the region of Lisbon, Portugal, comprising 3.7 million people during two different lockdown periods, scenarios of 40 and 60% mobility reduction. In the simulations, we assumed that the network of physical contact between people is that of a small world and computed the antibiotic resistance in human microbiomes after 180 days in the simulation. Our simulations show that reducing human contacts drives a reduction in the diversity of antibiotic resistance genes in human microbiomes. Kruskal–Wallis and Dunn’s pairwise tests show very strong evidence (p < 0.000, adjusted using the Bonferroni correction) of a difference between the four confinement regimes. The proportion of variability in the ranked dependent variable accounted for by the confinement variable was η2 = 0.148, indicating a large effect of confinement on the diversity of antibiotic resistance. We have shown that confinement and hygienic measures, in addition to reducing the spread of pathogenic bacteria in a human network, also reduce resistance and the need to use antibiotics.


2017 ◽  
Vol 2017 (2) ◽  
Author(s):  
Kwan Tze-wan

AbstractIn the Shuowen, one of the earliest comprehensive character dictionaries of ancient China, when discussing where the Chinese characters derive their structural components, Xu Shen proposed the dual constitutive principle of “adopting proximally from the human body, and distally from things around.” This dual emphasis of “body” and “things around” corresponds largely to the phenomenological issues of body or corporeality on the one hand, and lifeworld on the other. If we borrow Heidegger’s definition of Dasein as Being-in-the world, we can easily arrive at a reformulation of Xu Shen’s constitutive principle of the Chinese script as one that concerns “bodily Dasein.” By looking into various examples of script tokens we can further elaborate on how the Chinese make use not only of the body in general but various body parts, and how they differentiate their life world into material nature, living things, and a multifaceted world of equipment in forming a core basis of Chinese characters/components, upon which further symbolic manipulation such as “indication”, “phonetic borrowing”, semantic combination, and “annotative derivation”, etc. can be based. Finally, examples will be cited to show how in the Chinese scripts the human body (and its parts) might interact with other’s bodies (and their parts) or with “things around” (whether nature, living creatures, or artifacts) in various ways to cover the social, environmental, ritual, technical, economical, and even intellectual aspects of human experience. Bodily Dasein, so to speak, provides us with a new perspective of understanding and appreciating the entire scope of the Chinese script.


mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Benjamin C. Creekmore ◽  
Josh H. Gray ◽  
William G. Walton ◽  
Kristen A. Biernat ◽  
Michael S. Little ◽  
...  

ABSTRACT Gut microbial β-glucuronidase (GUS) enzymes play important roles in drug efficacy and toxicity, intestinal carcinogenesis, and mammalian-microbial symbiosis. Recently, the first catalog of human gut GUS proteins was provided for the Human Microbiome Project stool sample database and revealed 279 unique GUS enzymes organized into six categories based on active-site structural features. Because mice represent a model biomedical research organism, here we provide an analogous catalog of mouse intestinal microbial GUS proteins—a mouse gut GUSome. Using metagenome analysis guided by protein structure, we examined 2.5 million unique proteins from a comprehensive mouse gut metagenome created from several mouse strains, providers, housing conditions, and diets. We identified 444 unique GUS proteins and organized them into six categories based on active-site features, similarly to the human GUSome analysis. GUS enzymes were encoded by the major gut microbial phyla, including Firmicutes (60%) and Bacteroidetes (21%), and there were nearly 20% for which taxonomy could not be assigned. No differences in gut microbial gus gene composition were observed for mice based on sex. However, mice exhibited gus differences based on active-site features associated with provider, location, strain, and diet. Furthermore, diet yielded the largest differences in gus composition. Biochemical analysis of two low-fat-associated GUS enzymes revealed that they are variable with respect to their efficacy of processing both sulfated and nonsulfated heparan nonasaccharides containing terminal glucuronides. IMPORTANCE Mice are commonly employed as model organisms of mammalian disease; as such, our understanding of the compositions of their gut microbiomes is critical to appreciating how the mouse and human gastrointestinal tracts mirror one another. GUS enzymes, with importance in normal physiology and disease, are an attractive set of proteins to use for such analyses. Here we show that while the specific GUS enzymes differ at the sequence level, a core GUSome functionality appears conserved between mouse and human gastrointestinal bacteria. Mouse strain, provider, housing location, and diet exhibit distinct GUSomes and gus gene compositions, but sex seems not to affect the GUSome. These data provide a basis for understanding the gut microbial GUS enzymes present in commonly used laboratory mice. Further, they demonstrate the utility of metagenome analysis guided by protein structure to provide specific sets of functionally related proteins from whole-genome metagenome sequencing data.


2019 ◽  
Vol 36 (4) ◽  
pp. 1289-1290
Author(s):  
Patrick H Bradley ◽  
Katherine S Pollard

Abstract Summary Phylogenetic comparative methods are powerful but presently under-utilized ways to identify microbial genes underlying differences in community composition. These methods help to identify functionally important genes because they test for associations beyond those expected when related microbes occupy similar environments. We present phylogenize, a pipeline with web, QIIME 2 and R interfaces that allows researchers to perform phylogenetic regression on 16S amplicon and shotgun sequencing data and to visualize results. phylogenize applies broadly to both host-associated and environmental microbiomes. Using Human Microbiome Project and Earth Microbiome Project data, we show that phylogenize draws similar conclusions from 16S versus shotgun sequencing and reveals both known and candidate pathways associated with host colonization. Availability and implementation phylogenize is available at https://phylogenize.org and https://bitbucket.org/pbradz/phylogenize. Supplementary information Supplementary data are available at Bioinformatics online.


Virulence ◽  
2010 ◽  
Vol 1 (4) ◽  
pp. 299-303 ◽  
Author(s):  
Morten O.A. Sommer ◽  
George M. Church ◽  
Gautam Dantas

2002 ◽  
Vol 184 (15) ◽  
pp. 4259-4269 ◽  
Author(s):  
John W. Beaber ◽  
Bianca Hochhut ◽  
Matthew K. Waldor

ABSTRACT SXT is representative of a family of conjugative-transposon-like mobile genetic elements that encode multiple antibiotic resistance genes. In recent years, SXT-related conjugative, self-transmissible integrating elements have become widespread in Asian Vibrio cholerae. We have determined the 100-kb DNA sequence of SXT. This element appears to be a chimera composed of transposon-associated antibiotic resistance genes linked to a variety of plasmid- and phage-related genes, as well as to many genes from unknown sources. We constructed a nearly comprehensive set of deletions through the use of the one-step chromosomal gene inactivation technique to identify SXT genes involved in conjugative transfer and chromosomal excision. SXT, unlike other conjugative transposons, utilizes a conjugation system related to that encoded by the F plasmid. More than half of the SXT genome, including the composite transposon-like structure that contains its antibiotic resistance genes, was not required for its mobility. Two SXT loci, designated setC and setD, whose predicted amino acid sequences were similar to those of the flagellar regulators FlhC and FlhD, were found to encode regulators that activate the transcription of genes required for SXT excision and transfer. Another locus, designated setR, whose gene product bears similarity to lambdoid phage CI repressors, also appears to regulate SXT gene expression.


2021 ◽  
Author(s):  
Lucia Maestre-Carballa ◽  
Vicente Navarro ◽  
Manuel Martinez-Garcia

Abstract BackgroundIn response to the global antibiotic resistance crisis, efforts have been focused on gaining a better understanding of resistomes (sets of antibiotic resistance genes (ARGs)) and the dispersion of ARGs in nature. A comprehensive metagenomic characterization of the human body resistome is paramount for laying the foundation to develop a better strategy to address this health concern. Here, we study the resistomes of 771 samples from five major body parts of healthy subjects from the Human Microbiome Project (HMP). In line with the One Health concept (WHO), we also investigated the presence of ARGs from the HMP in 272 pristine environments. ResultsOf all the detected HMP genes/proteins (9.17E+07), 40,816 were ARGs showing high interindividual and inter-body-site abundance variability. Nares had the highest ARG abundance (2.18±2.64 ARGs/Mb; ≈5.5 ARG per bacterial genome), while the gut (0.34±0.34 ARGs/Mb; ≈1.3 ARG per bacterial genome), which also showed the highest richness of different ARG types, had the lowest abundance. Fluroquinolone resistance genes were the most abundant antibiotic resistance gene family, followed by MLS or tetracycline resistance genes, depending on the body site. From all the detected ARGs, we found 366 different ARG types, with parC R (fluoroquinolone resistance) being the most abundant in the oral cavity, mprF (peptide antibiotic resistance) in the skin and nares, and tetQ (tetracycline resistance) in the gut and vagina. Most of the ARGs belonged to common bacterial commensals, and many of them were also multidrug resistance genes and were more abundant in the nares and vagina. The total number of ARGs from the HMP data (n=34) detected in pristine environments (266 samples) was negligible, and most of them (73%) were classified as housekeeping genes in autochthonous bacteria having known mutations conferring antibiotic resistance (natural reservoirs). A significant fraction of ARGs (24%) in pristine environments were actually from exogenous contaminants. The detection of identical HMP ARGs in autochthonous bacteria was extremely infrequent (3%). Conclusions Our results comprehensively reveal the resistomes from all body parts and HMP samples that can serve as a baseline for comparison for long-term survey and monitoring of human resistome variations. Finally, our data provide hope, since the spread of common ARGs from the HMP data to pristine environments thus far remains very unlikely.


2021 ◽  
Author(s):  
Bruna Verônica Azevedo Gois ◽  
Kenny da Costa Pinheiro ◽  
Wylerson Guimarães Nogueira ◽  
Andressa de Oliveira Aragão ◽  
Ana Lídia Cavalcante Queiroz ◽  
...  

Abstract Background: Despite the importance of understanding the ecology of freshwater viruses, there are not many studies on the issue when compared to marine viruses. The microbiological interactions that occur in these environments are still poorly known, especially between bacteriophages and their host bacteria, as well as between cyanophages and cyanobacteria. Lake Bologna, from Belém, capital of the Brazilian State of Pará, is a source of water that supplies the city and its metropolitan region, yet it remains unexplored regarding the contents of its virome and viral diversity composition. Therefore, this work's main aim is to clarify in terms of taxonomic diversity the species of DNA viruses that are present in this lake, especially bacteriophages and cyanophages, since they can act both as transducers of resistance genes and reporters of water quality for human consumption. Results: For this work, we used the metagenomic sequencing data generated by Alves et al. (2020), and we analyzed it at the taxonomic level using the tools Kraken2, Bracken, and Pavian; later, the data was assembled using Genome Detective, which performs assembly of viruses. The results observed in this work suggest the existence of a widely diverse viral community and an established microbial phage regulated dynamics in the Lake Bolonha. Conclusions: This work is the first-ever to describe the virome of Lake Bolonha using a metagenomic approach based on high-throughput sequencing, as it contributes to the understanding of water-related public health concerns regarding the spreading of antibiotic resistance genes and population control of native bacteria and cyanobacteria.


mBio ◽  
2012 ◽  
Vol 3 (6) ◽  
Author(s):  
Geraint B. Rogers ◽  
Kenneth D. Bruce

ABSTRACT Recent studies have greatly extended our understanding of the microbiota present in and on the human body. Here, advanced sequencing strategies have provided unprecedented analytical power. The important implications that the emerging data have for human health emphasize the need to intensify research in this area (D. A. Relman, Nature 486:194-195, 2012). It is already clear from these studies that the microbiotas characterized in different body locations of healthy individuals are both complex and diverse (The Human Microbiome Project Consortium, Nature 486:215-221). These studies also provide a point of contrast for investigations that aim to characterize the microbiota present in disease conditions. In this regard, Madan et al. (mBio 3(4):e00251-12, 2012) monitored the development over time of microbiota in the oropharynges and feces of neonates with cystic fibrosis and explored the potential for interactions between these complex microbial systems.


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