Mechanisms of Chromium and Uranium Toxicity in Pseudomonas stutzeri RCH2 Grown under Anaerobic Nitrate-Reducing Conditions

Thorgersen, Michael P.; Lancaster, W. Andrew; Ge, Xiaoxuan; Zane, Grant M.; Wetmore, Kelly M.; Vaccaro, Brian J.; Poole, Farris L.; Younkin, Adam D.; Deutschbauer, Adam M.; Arkin, Adam P.; Wall, Judy D.; Adams, Michael W. W.

doi:10.3389/fmicb.2017.01529

Cited by 43 publications

(26 citation statements)

References 58 publications

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“…Macrolides, such as clarithromycin, are key drugs for treatment of MAC infections. The development of clarithromycin resistance, that makes the therapy prone to fail [ 56 ], has been mainly attributed to mutational alterations of the 23S rRNA gene and to overexpression of EPs [ 15 ]. In particular, the upregulation of EP activity, induced upon drug exposure, can significantly decrease the intracellular concentration of clarithromycin, reducing its clinical efficacy.…”

Section: Mycobacterium Avium Complex (Mac)mentioning

confidence: 99%

“…Infections caused by NTM are often difficult to treat since therapy, that needs the use of a combination drug regimen, is long, expensive, and more toxic and more likely to fail than tuberculosis therapy [ 13 , 14 ]. The highly hydrophobic lipid-rich cell wall constitutes a strong barrier to the penetration of various drugs, representing a major contributor for intrinsic resistance of NTM to many antimicrobial compounds currently available [ 15 ], thus encouraging an urgent need for the development of new drugs for the treatment of mycobacterial infections [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Efflux Pump Inhibitors against Nontuberculous Mycobacteria

Rindi

2020

IJMS

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Over the last years, nontuberculous mycobacteria (NTM) have emerged as important human pathogens. Infections caused by NTM are often difficult to treat due to an intrinsic multidrug resistance for the presence of a lipid-rich outer membrane, thus encouraging an urgent need for the development of new drugs for the treatment of mycobacterial infections. Efflux pumps (EPs) are important elements that are involved in drug resistance by preventing intracellular accumulation of antibiotics. A promising strategy to decrease drug resistance is the inhibition of EP activity by EP inhibitors (EPIs), compounds that are able to increase the intracellular concentration of antimicrobials. Recently, attention has been focused on identifying EPIs in mycobacteria that could be used in combination with drugs. The aim of the present review is to provide an overview of the current knowledge on EPs and EPIs in NTM and also, the effect of potential EPIs as well as their combined use with antimycobacterial drugs in various NTM species are described.

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Section: Mycobacterium Avium Complex (Mac)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efflux Pump Inhibitors against Nontuberculous Mycobacteria

Rindi

2020

IJMS

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“…For example, in a study of denitrification rates in saltmarsh sediments, it was reported that initial denitrification rates were inhibited by several metals at 1 g/liter, including Pb, Ni, Cr, Zn, Cu, Fe, and Cd (24). Similarly, whole-genome fitness assays conducted on a model denitrifying organism, Pseudomonas stutzeri RCH2, grown under denitrifying conditions, revealed that disruptions to nitrate reductase and denitrification-related genes resulted in decreased fitness of the organism when grown in the presence of elevated concentrations of several different metals, including Cu, Zn, Cr, and U (39,40). The ORR organisms that we isolated must therefore have molecular and physical mechanisms of metal resistance that allow them to survive in the extreme ORR environment, and the nature of those mechanisms is currently under study.…”

Section: Discussionmentioning

confidence: 98%

Nitrate-Utilizing Microorganisms Resistant to Multiple Metals from the Heavily Contaminated Oak Ridge Reservation

Thorgersen

Poole

et al. 2019

Appl Environ Microbiol

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Contamination of environments with nitrate generated by industrial processes and the use of nitrogen-containing fertilizers is a growing problem worldwide. While nitrate can be removed from contaminated areas by microbial denitrification, nitrate frequently occurs with other contaminants, such as heavy metals, that have the potential to impede the process. Here, nitrate-reducing microorganisms were enriched and isolated from both groundwater and sediments at the Oak Ridge Reservation (ORR) using concentrations of nitrate and metals (Al, Mn, Fe, Co, Ni, Cu, Cd, and U) similar to those observed in a contaminated environment at ORR. Seven new metal-resistant, nitrate-reducing strains were characterized, and their distribution across both noncontaminated and contaminated areas at ORR was examined. While the seven strains have various pH ranges for growth, carbon source preferences, and degrees of resistance to individual and combinations of metals, all were able to reduce nitrate at similar rates both in the presence and absence of the mixture of metals found in the contaminated ORR environment. Four strains were identified in groundwater samples at different ORR locations by exact 16S RNA sequence variant analysis, and all four were found in both noncontaminated and contaminated areas. By using environmentally relevant metal concentrations, we successfully isolated multiple organisms from both ORR noncontaminated and contaminated environments that are capable of reducing nitrate in the presence of extreme mixed-metal contamination. IMPORTANCE Nitrate contamination is a global issue that affects groundwater quality. In some cases, cocontamination of groundwater with nitrate and mixtures of heavy metals could decrease microbially mediated nitrate removal, thereby increasing the duration of nitrate contamination. Here, we used metal and nitrate concentrations that are present in a contaminated site at the Oak Ridge Reservation to isolate seven metal-resistant strains. All were able to reduce nitrate in the presence of high concentrations of a mixture of heavy metals. Four of seven strains were located in pristine as well as contaminated sites at the Oak Ridge Reservation. Further study of these nitrate-reducing strains will uncover mechanisms of resistance to multiple metals that will increase our understanding of the effect of nitrate and metal contamination on groundwater microbial communities.

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“…Data from various studies with model denitrifiers (Giannopoulos et al, ; Olaya‐Abril et al, ; Gaimster et al, ; Gaimster et al, ; Kohlmann et al, ; Thorgersen et al, ) and nitrifiers (Qin et al, ; Cho et al, ; Wei et al, ; Mellbye et al, ; Pérez et al, ; Lu et al, ; Carini et al, ) is available for integration into models. However, soil and aquatic environments host complex microbial communities that could differ substantially in terms of the regulation and activity with respect to their nitrogen‐cycling pathways (Lycus et al, ).…”

Section: Current and Future Methods For Assessing Sources And Sinks Omentioning

confidence: 99%

Systems biology approaches towards predictive microbial ecology

Otwell

Lomana

Gibbons

et al. 2018

Environmental Microbiology

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Through complex interspecies interactions, microbial processes drive nutrient cycling and biogeochemistry. However, we still struggle to predict specifically which organisms, communities and biotic and abiotic processes are determining ecosystem function and how environmental changes will alter their roles and stability. While the tools to create such a predictive microbial ecology capability exist, cross-disciplinary integration of high-resolution field measurements, detailed laboratory studies and computation is essential. In this perspective, we emphasize the importance of pursuing a multiscale, systems approach to iteratively link ecological processes measured in the field to testable hypotheses that drive high-throughput laboratory experimentation. Mechanistic understanding of microbial processes gained in controlled lab systems will lead to the development of theory that can be tested back in the field. Using N O production as an example, we review the current status of field and laboratory research and layout a plausible path to the kind of integration that is needed to enable prediction of how N-cycling microbial communities will respond to environmental changes. We advocate for the development of realistic and predictive gene regulatory network models for environmental responses that extend from single-cell resolution to ecosystems, which is essential to understand how microbial communities involved in N O production and consumption will respond to future environmental conditions.

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Mechanisms of Chromium and Uranium Toxicity in Pseudomonas stutzeri RCH2 Grown under Anaerobic Nitrate-Reducing Conditions

Cited by 43 publications

References 58 publications

Efflux Pump Inhibitors against Nontuberculous Mycobacteria

Efflux Pump Inhibitors against Nontuberculous Mycobacteria

Nitrate-Utilizing Microorganisms Resistant to Multiple Metals from the Heavily Contaminated Oak Ridge Reservation

Systems biology approaches towards predictive microbial ecology

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