环境微生物的抗生素抗性和抗性组

环境和医疗实践中广泛存在的细菌抗生素抗性已经成为食品安全和人类健康领域的主要威胁。近年来的研究表明,病原菌主要通过水平基因转移而不是基因突变获得抗性,大量的研究支持病原微生物抗生素抗性基因的环境来源。系统论述了环境微生物抗生素抗性起源、进化及病原菌抗性基因与环境抗生素抗性组相互之间的交叉传播和水平转移机制,介绍了近年来环境微生物抗生素抗性组生态和进化生物学研究的最新进展和方法学应用。     

Protein–protein interaction networks suggest different targets have different propensities for triggering drug resistance

Emergence of drug resistance is a major problem in the treatment of many diseases including tuberculosis. To tackle the problem from a wholistic perspective, it is essential to understand the molecular mechanisms by which bacteria acquire drug resistance using a systems approach. Availability of genome-scale data of expression profiles under different drug exposed conditions and protein–protein interactions, makes it feasible to reconstruct and analyze systems-level models. A number of proteins involved in different resistance mechanisms, referred to as the resistome are identified from literature. The interaction of the drug directly with the resistome is unable to explain most resistance processes adequately, including that of increased mutations in the target’s binding site. We recently hypothesized that some communication might exist from the drug environment to the resistome to trigger emergence of drug resistance. We report here a network based approach to identify most plausible paths of such communication in Mycobacterium tuberculosis. Networks capturing both structural and functional linkages among various proteins were weighted based on gene expression profiles upon exposure to specific drugs and betweenness centrality of the interactions. Our analysis suggests that different drug targets and hence different drugs could trigger the resistome to different extents and through different routes. The identified paths correlate well with the mechanisms known through experiment. Some examples of the top ranked hubs in multiple drug specific networks are PolA, FadD1, CydA, a monoxygenase and GltS, which could serve as co-targets, that could be inhibited in order to retard resistance related communication in the cell.     

Wastewater pollution differently affects the antibiotic resistance gene pool and biofilm bacterial communities across streambed compartments

Wastewater discharges introduce antibiotic residues and antibiotic‐resistant bacteria (ARB) into surface waters. Both inputs directly affect the streambed resistome, either by exerting a selective pressure that favour the proliferation of resistant phenotypes or by enriching the resident communities with wastewater‐associated ARB. Here, we investigated the impact of raw and treated urban wastewater discharges on epilithic (growing on rocks) and epipsammic (growing on sandy substrata) streambed biofilms. The effects were assessed by comparing control and impact sites (i) on the composition of bacterial communities; (ii) on the abundance of twelve antibiotic resistance genes (ARGs) encoding resistance to β‐lactams, fluoroquinolones, sulphonamides, tetracyclines, macrolides and vancomycin, as well as the class 1 integron‐integrase gene (intI1); (iii) on the occurrence of wastewater‐associated bacteria, including putative pathogens, and their potential linkage to target ARGs. We measured more pronounced effects of raw sewage than treated wastewater at the three studied levels. This effect was especially noticeable in epilithic biofilms, which showed a higher contribution of wastewater‐associated bacteria and ARB than in epipsammic biofilms. Comparison of correlation coefficients obtained between the relative abundance of both target ARGs and operational taxonomic units classified as either potential pathogens or nonpathogens yielded significant higher correlations between the former category and genes intI1, sul1, sul2 and ermB. Altogether, these results indicate that wastewater‐associated micro‐organisms, including potential pathogens, contribute to maintain the streambed resistome and that epilithic biofilms appear as sensitive biosensors of the effect of wastewater pollution in surface waters.     

Antibiotic Treatment Drives the Diversification of the Human Gut Resistome

Despite the documented antibiotic-induced disruption of the gut microbiota, the impact of antibiotic intake on strain-level dynamics, evolution of resistance genes, and factors influencing resistance dissemination potential remains poorly understood. To address this gap we analyzed public metagenomic datasets from 24 antibiotic treated subjects and controls, combined with an in-depth prospective functional study with two subjects investigating the bacterial community dynamics based on cultivation-dependent and independent methods. We observed that shortterm antibiotic treatment shifted and diversified the resistome composition, increased the average copy number of antibiotic resistance genes, and altered the dominant strain genotypes in an individual-specific manner. More than 30% of the resistance genes underwent strong differentiation at the single nucleotide level during antibiotic treatment. We found that the increased potential for horizontal gene transfer, due to antibiotic administration, was ～3-fold stronger in the differentiated resistance genes than the non-differentiated ones. This study highlights how antibiotic treatment has individualized impacts on the resistome and strain level composition, and drives the adaptive evolution of the gut microbiota.