Antibiotic resistance is ancient: implications for drug discovery

doi:10.1016/j.tim.2012.01.002

Trends in Microbiology

Volume 20, Issue 4, April 2012, Pages 157-159

https://doi.org/10.1016/j.tim.2012.01.002 Get rights and content

An unfailing observation over the past 70 years is that resistance to all antibiotics emerges eventually after use in the clinic. Where does this resistance come from? Recent work has shown that antibiotic resistance genes are common in metagenomes of ancient sediments. This prevalence of resistance, well before the use of antibiotics, denotes the importance of taking microbial chemical ecology and deep metagenomic profiling into account in the development and use of antibiotics.

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Metagenomic insights into the antibiotic resistome in freshwater and seawater from an Antarctic ice-free area
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The comprehensive profiles of antibiotic resistance genes (ARGs) in the Antarctic water environments and their potential health risks are not well understood. The present study characterized the bacterial community compositions and ARG profiles of freshwater (11 samples) and seawater (28 samples) around the Fildes Region (an ice-free area in Antarctica) using a shotgun metagenomic sequencing approach for the first time. There were significant differences in the compositions of the bacterial community and ARG profiles between freshwater and seawater. In the 39 water samples, 114 ARG subtypes belonging to 15 ARG types were detectable. In freshwater, the dominant ARGs were related to multidrug and rifamycin resistance. In seawater, the dominant ARGs were related to peptide, multidrug, and beta-lactam resistance. Both the bacterial community compositions and ARG profiles were significantly related to certain physicochemical properties (e.g., pH, salinity, NO₃⁻). Procrustes analysis revealed a significant correlation between the bacterial community compositions and ARG profiles of freshwater and seawater samples. A total of 31 metagenome-assembled genomes (MAGs) carrying 35 ARG subtypes were obtained and identified. The results will contribute to a better evaluation of the ARG contamination in relation to human health in the Antarctic aquatic environments.
The formation of specific bacterial communities contributes to the enrichment of antibiotic resistance genes in the soil plastisphere
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Soil serves as a major reservoir of both antibiotic resistance genes (ARGs) and microplastics. However, the characteristics of the antibiotic resistome in the soil plastisphere remain largely unknown. In this study, we used metagenomic approaches to reveal the changing patterns of ARGs and the bacterial community and their associations in response to three types of microplastics (light density polyethylene, LDPE; polypropylene, PP; polystyrene, PS) using particles 550 µm or 75 µm in diameter. The total ARG abundances significantly increased in the plastisphere and varied across plastic types. The LDPE plastisphere had the highest ARG total abundance and lowest Shannon diversity index, indicating that this plastic had the most severe negative impact on soil bacterial diversity. The PP plastisphere contained higher relative abundances of the pathogenic bacteria Acinetobacter johnsonii and Escherichia coli, demonstrating the higher pathogenic risk of the microbial communities enriched in the plastisphere. Specifically, multidrug resistance genes (ceoB and MuxB) co-existed with more than four microbial taxa, increasing the potential risk of ARG spread in pathogenic bacteria. These findings implied that the plastisphere acts as a hotspot for acquiring and spreading antibiotic resistance and may have long-term negative effects on the soil ecosystem and human health.
Impacts of farmland application of antibiotic-contaminated manures on the occurrence of antibiotic residues and antibiotic resistance genes in soil: A meta-analysis study
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A meta-analysis of 94 published studies was conducted to explore the impacts of farmland application of antibiotic-contaminated manures on antibiotic concentrations and ARG abundances in manure-amended soil. Forty-nine antibiotics were reported, in which chlortetracycline, oxytetracycline, doxycycline, tetracycline, enrofloxacin, ciprofloxacin and norfloxacin were the most prevalent and had relatively high concentrations. The responses of ARG and mobile genetic element (MGE) abundances to farmland application of antibiotic-contaminated manures varied considerably under different management strategies and environmental settings. On average, compared to unamended treatments, farmland application of antibiotic-contaminated manures significantly increased the total ARG and MGE abundances by 591% and 351%, respectively (P < 0.05). Of all the included ARG classes, the largest increase was found for sulfonamide resistance genes (1121%), followed by aminoglycoside (852%) and tetracycline (763%) resistance genes. Correlation analysis suggested that soil organic carbon (SOC) was significantly negatively correlated with antibiotic concentrations in manured soil (P < 0.05) due to the formation of covalent bonds and nonextractable residues. Soil silt content was significantly positively correlated with antibiotic concentration (P < 0.05), which was attributed to greater sorption capacities. The ARG abundances were significantly positively correlated with soil silt content, antibiotic concentrations, mean annual temperature, SOC, MGEs and soil pH (P < 0.05), suggesting that changes in these factors may shape the ARG profiles. Collectively, these findings advanced our understanding of the occurrence of antibiotics and ARGs in manure-amended soil and potential factors affecting them and will contribute to better management of these contaminants in future agricultural production.
The enhanced catalytic degradation of sulfamethoxazole over Fe@nitrogen-doped carbon-supported nanocomposite: Insight into the mechanism
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Citation Excerpt :
Antibiotics are widely used in aquatic environments and are highly persistent, which carries a high toxic potential to aquatic organisms [1]. Moreover, the overuse of antibiotics has also contributed to the rapid proliferation of antibiotic-resistant bacteria (ARB) and antibiotics resistance genes (ARGs), which will lead to more serious public health risks [2,3]. Sulfamethoxazole (SMX), one of the sulfonamides (SAs) antibiotics, is widely used in veterinary practice due to its advantages in terms of cost, stability and antibiotic activity, and is the most frequently detected antibiotic in the aqueous environment in China [4–6].
An environmentally friendly Fe@nitrogen-doped carbon nanocomposite catalyst (Fe@N-CNs) was prepared via a facile and economical process using carboxymethyl chitosan (CMCs) hydrogel as a template to achieve Fe-anchoring and N-doping simultaneously for peroxymonosulfate (PMS) activation to efficiently degrade sulfamethoxazole (SMX). The “core–shell” structure of Fe@N-CNs displayed that Fe nanoparticles identified as Fe₃C and Fe₃N were encapsulated in nitrogen-doped carbon nanosheets. The formation of Fe_xN_y sites and the high content of graphitic N obtained from CMCs facilitated the catalytic reaction. With excellent catalytic activity to achieve complete degradation of SMX in less than 10 min, Fe@N-CNs/PMS system also exhibited stable catalytic degradation efficiency over a wide pH range (3.0–9.0) and under high-salinity conditions. Singlet oxygen was identified as the dominant reactive species in catalytic oxidation and played a vital role in the non-radical pathway. The potential SMX degradation pathway and mechanism in the Fe@N-CNs/PMS reaction system were proposed according to DFT calculations and product detection results. Quantitative structure–activity relationship (QSAR) prediction verified the efficient elimination of SMX degradation products toxicity. Moreover, the Fe@N-CNs/PMS system was also confirmed to be effective towards the inactivation of antibiotic-resistant bacteria (ARB) and antibiotics resistance genes (ARGs).
Animal corpse degradation enriches antibiotic resistance genes but remains recalcitrant in drinking water microcosm
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Serious concerns have been raised regarding resistomes caused by corpse decomposition in the aquatic environment, which has posed threats to the water environment and human health. However, antibiotic resistance genes (ARGs) in large-volume tap water and their temporal stability during corpse decay are poorly explored. Here, high-throughput quantitative polymerase chain reaction (HT-qPCR) and amplicon sequencing were applied to profile ARGs and bacterial communities in experimental and control groups containing 50 L of tap water at 7th, 15th and 100th day during corpse decomposition. Our results suggested that most of the ARGs in experimental group had higher abundance compared with the control group independent of time. Some ARGs’ absolute abundance like tetracycline and beta-lactamase was even enriched by 259 – 413,640-folds during corpse decay. Twelve opportunistic pathogens, especially Burkholderia, Legionella and Halomonas, remarkably increased as decomposition proceeded. Furthermore, network analysis showed that opportunistic pathogens were significantly associated with ARGs. Our results emphasize that corpse decay increases the abundance and diversity of ARGs in large-volume drinking water independent of time while exhibiting temporal persistence of ARGs, thereby uncovering the harmful effects of animal cadavers. Our study also provides valuable suggestions for the risk assessment and management of source water caused by corpse decay.

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Trends in Microbiology

Forum: Science & SocietyAntibiotic resistance is ancient: implications for drug discovery

Fix the antibiotics pipeline

Nature

Origins and evolution of antibiotic resistance

Microbiol. Mol. Biol. Rev.

Kinship and diversification of bacterial penicillin-binding proteins and beta-lactamases

Antimicrob. Agents Chemother.

Structure-based phylogenies of the serine beta-lactamases

J. Mol. Evol.

Antibiotic resistance is ancient

Nature

Antibiotic discovery from actinomycetes: Will a renaissance follow the decline and fall?

SIM News

Sampling the antibiotic resistome

Science

Forum: Science & Society
Antibiotic resistance is ancient: implications for drug discovery