Abstract:Resistance to antibiotics is an important and timely problem of contemporary medicine. Rapid evolution of resistant bacteria calls for new preventive measures to slow down this process, and a longer-term progress cannot be achieved without a good understanding of the mechanisms through which drug resistance is acquired and spreads in microbial populations. Here, we discuss recent experimental and theoretical advances in our knowledge how the dynamics of microbial populations affects the evolution of antibiotic… Show more
“… A proposed scheme of workflow illustrating the use of (A) live imaging technologies to visualize and track the growth and evolution of probiotic bacteria in real-time (Baym et al, 2016), (B,C) advanced molecular tools for the broad coverage and high resolution system level detection and gene expression analysis (Marondedze et al, 2014) and (D) powerful computational approaches for the formation of predictive models simulating the behavior of probiotic bacteria based on laboratory data (Waclaw, 2016), for the assessment of the risk of antibiotic resistance contributed by commercial probiotic strains and their long-term consumption to human health. This integrative approach should be applied in studies that consider the different compositions of the gut microflora such as the presence of a consortia of probiotic strains and pathogens as well as a gradient of antibiotic pressures, and their growth and colonization dynamics in response to various spatial and temporal factors.…”
Section: Assessing the Risk Of Antibiotic Resistance In Probiotics Ofmentioning
confidence: 99%
“…For instance, computational models revealed that bacteria may switch to an alternative phenotype [e.g., consuming a different food source (Solopova et al, 2014)] that is less sensitive to a new and unfavorable environmental condition, can afford bacteria time to develop compensatory mutations that offset the effect of the deleterious mutation and regain fitness (Greulich et al, 2012; Waclaw, 2016). The use of mathematical models to simulate how phenotypic switching can provide a larger pool of bacteria to evolve genetic resistance to antibiotics has been previously reviewed (Levin and Rozen, 2006).…”
Section: Assessing the Risk Of Antibiotic Resistance In Probiotics Ofmentioning
Probiotic bacteria are known to harbor intrinsic and mobile genetic elements that confer resistance to a wide variety of antibiotics. Their high amounts in dietary supplements can establish a reservoir of antibiotic resistant genes in the human gut. These resistant genes can be transferred to pathogens that share the same intestinal habitat thus resulting in serious clinical ramifications. While antibiotic resistance of probiotic bacteria from food, human and animal sources have been well-documented, the resistant profiles of probiotics from dietary supplements have only been recently studied. These products are consumed with increasing regularity due to their health claims that include the improvement of intestinal health and immune response as well as prevention of acute and antibiotic-associated diarrhea and cancer; but, a comprehensive risk assessment on the spread of resistant genes to human health is lacking. Here, we highlight recent reports of antibiotic resistance of probiotic bacteria isolated from dietary supplements, and propose complementary strategies that can shed light on the risks of consuming such products in the context of a global widespread of antibiotic resistance. In concomitant with a broader screening of antibiotic resistance in probiotic supplements is the use of computational simulations, live imaging and functional genomics to harvest knowledge on the evolutionary behavior, adaptations and dynamics of probiotics studied in conditions that best represent the human gut including in the presence of antibiotics. The underlying goal is to enable the health benefits of probiotics to be exploited in a responsible manner and with minimal risk to human health.
“… A proposed scheme of workflow illustrating the use of (A) live imaging technologies to visualize and track the growth and evolution of probiotic bacteria in real-time (Baym et al, 2016), (B,C) advanced molecular tools for the broad coverage and high resolution system level detection and gene expression analysis (Marondedze et al, 2014) and (D) powerful computational approaches for the formation of predictive models simulating the behavior of probiotic bacteria based on laboratory data (Waclaw, 2016), for the assessment of the risk of antibiotic resistance contributed by commercial probiotic strains and their long-term consumption to human health. This integrative approach should be applied in studies that consider the different compositions of the gut microflora such as the presence of a consortia of probiotic strains and pathogens as well as a gradient of antibiotic pressures, and their growth and colonization dynamics in response to various spatial and temporal factors.…”
Section: Assessing the Risk Of Antibiotic Resistance In Probiotics Ofmentioning
confidence: 99%
“…For instance, computational models revealed that bacteria may switch to an alternative phenotype [e.g., consuming a different food source (Solopova et al, 2014)] that is less sensitive to a new and unfavorable environmental condition, can afford bacteria time to develop compensatory mutations that offset the effect of the deleterious mutation and regain fitness (Greulich et al, 2012; Waclaw, 2016). The use of mathematical models to simulate how phenotypic switching can provide a larger pool of bacteria to evolve genetic resistance to antibiotics has been previously reviewed (Levin and Rozen, 2006).…”
Section: Assessing the Risk Of Antibiotic Resistance In Probiotics Ofmentioning
Probiotic bacteria are known to harbor intrinsic and mobile genetic elements that confer resistance to a wide variety of antibiotics. Their high amounts in dietary supplements can establish a reservoir of antibiotic resistant genes in the human gut. These resistant genes can be transferred to pathogens that share the same intestinal habitat thus resulting in serious clinical ramifications. While antibiotic resistance of probiotic bacteria from food, human and animal sources have been well-documented, the resistant profiles of probiotics from dietary supplements have only been recently studied. These products are consumed with increasing regularity due to their health claims that include the improvement of intestinal health and immune response as well as prevention of acute and antibiotic-associated diarrhea and cancer; but, a comprehensive risk assessment on the spread of resistant genes to human health is lacking. Here, we highlight recent reports of antibiotic resistance of probiotic bacteria isolated from dietary supplements, and propose complementary strategies that can shed light on the risks of consuming such products in the context of a global widespread of antibiotic resistance. In concomitant with a broader screening of antibiotic resistance in probiotic supplements is the use of computational simulations, live imaging and functional genomics to harvest knowledge on the evolutionary behavior, adaptations and dynamics of probiotics studied in conditions that best represent the human gut including in the presence of antibiotics. The underlying goal is to enable the health benefits of probiotics to be exploited in a responsible manner and with minimal risk to human health.
“…We further use the model to recommend future strategies for prevention of this process. 15 One recent study has further looked at the effect of diffusion-based drug gradients on the effective outcome of population diversity and heterogeneity [8]. This heterogeneity is evident in the biological literature but is yet to be explained by existing mathematical models.…”
Although novel targeted therapies have significantly improved the overall survival of patients with advanced melanoma, understanding and combatting drug resistance remains a major clinical challenge. Using partial differential equations, we describe the evolution of a cellular population through time, space, and phenotype dimensions, in the presence of various drug species. We then use this framework to explore models in which resistance is attained by either mutations (irreversible) or plasticity (reversible). Numerical results suggest that punctuated evolutionary assumptions are more consistent with results obtained from murine melanoma models than gradual evolution. Furthermore, in the context of an evolving tumour cell population, sequencing the treatment, for instance applying immunotherapy before BRAF inhibitors, can increase treatment effectiveness. However, drug strategies which showed success within a spatially homogeneous tumour environment were unsuccessful under heterogeneous conditions, suggesting that spatio-environmental heterogeneity may be the greatest challenge to tumour therapies. Plastic metabolic models are additionally capable of reproducing the characteristic resistant tumour volume curves and predicting re-sensitisation to secondary waves of treatment observed in patient derived xenograft (PDX) melanomas treated with MEK and BRAF inhibitors. Nevertheless, secondary relapse due to a pre-adapted subpopulation, remaining after the first wave of treatment, results in a more rapid development of resistance. Our model provides a framework through which tumour resistance can be understood and would suggest that carefully phased treatments may be able to overcome the development of long-term resistance in melanoma.
“…For half a century, antibiotics derived from microorganisms have become the leading drugs in different clinical fields due to their distinct structures and excellent activities [2,3]. However, the emerging of drug-resistant bacteria and drug-resistant tumors has prompted people to search for new drugs and novel mechanisms of action [4,5]. More recently, the marine environment is considered as an abundant microbial resource due to its complex ecological environment and relatively harsh living conditions [6,7], which implies there are enormous unexplored secondary metabolites and their biosynthetic gene clusters to be discovered and characterized.…”
Four novel bioactive tetrahydroanthra-γ-pyrone compounds, shellmycin A–D (1–4), were isolated from the marine Streptomyces sp. shell-016 derived from a shell sediment sample collected from Binzhou Shell Dike Island and Wetland National Nature Reserve, China. The structures of these four compounds were established by interpretation of 1D and 2D NMR and HR-MS data, in which the absolute configuration of 1 was confirmed by single crystal X-ray diffraction, and compound 3 and 4 are a pair of stereoisomers. Compound 1–4 exhibited cytotoxic activity against five cancer cell lines with the IC50 value from 0.69 μM to 26.3 μM. Based on their structure–activity relationship, the putative biosynthetic pathways of these four compounds were also discussed.
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