Amy Nava
Research Scientist, Molecular and Cellular Physiology
Contingent OTP 1, Pathology Sponsored Projects #2
All Publications
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Molecular mechanism of exchange coupling in CLC chloride/proton antiporters.
Nature communications
2026
Abstract
The ubiquitous CLC membrane transporters are unique in their ability to exchange anions for cations. Despite extensive study, there is no mechanistic model that fully explains their 2:1 Cl‒/H+ stoichiometric exchange mechanism. Here, we provide such a model. Using differential hydrogen-deuterium exchange mass spectrometry, cryo-EM structure determination, and molecular dynamics simulations, we uncovered conformational dynamics in CLC-ec1, a bacterial CLC homolog that has served as a paradigm for this family of transporters. Simulations based on a cryo-EM structure at pH 3 revealed critical steps in the transport mechanism, including release of Cl‒ ions to the extracellular side, opening of the inner gate, and water wires that facilitate H+ transport. Surprisingly, these water wires occurred independently of Cl‒ binding, prompting us to reassess the relationship between Cl‒ binding and Cl‒/H+ coupling. Using isothermal titration calorimetry and quantitative flux assays on mutants with reduced Cl‒ binding affinity, we conclude that, while Cl‒ binding is necessary for coupling, even weak binding can support Cl‒/H+ coupling. By integrating our findings with existing literature, we establish a complete and efficient CLC 2:1 Cl‒/H+ exchange mechanism.
View details for DOI 10.1038/s41467-025-68098-1
View details for PubMedID 41507156
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Micro, Nano, and Biodegradable Plastics: Hidden Threats to Plant Health and Soil Function
REVIEWS OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY
2025; 264 (1)
View details for DOI 10.1007/s44169-025-00105-4
View details for Web of Science ID 001649797300001
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Molecular mechanism of exchange coupling in CLC chloride/proton antiporters.
bioRxiv : the preprint server for biology
2025
Abstract
The ubiquitous CLC membrane transporters are unique in their ability to exchange anions for cations. Despite extensive study, there is no mechanistic model that fully explains their 2:1 Cl‒/H+ stoichiometric exchange mechanism. Here, we provide such a model. Using differential hydrogen-deuterium exchange mass spectrometry, cryo-EM structure determination, and molecular dynamics simulations, we uncovered new conformational dynamics in CLC-ec1, a bacterial CLC homolog that has served as a paradigm for this family of transporters. Simulations based on a cryo-EM structure at pH 3 revealed critical steps in the transport mechanism, including release of Cl‒ ions to the extracellular side, opening of the inner gate, and novel water wires that facilitate H+ transport. Surprisingly, these water wires occurred independently of Cl‒ binding, prompting us to reassess the relationship between Cl‒ binding and Cl‒/H+ coupling. Using isothermal titration calorimetry and quantitative flux assays on mutants with reduced Cl‒ binding affinity, we conclude that, while Cl‒ binding is necessary for coupling, even weak binding can support Cl‒/H+ coupling. By integrating our findings with existing literature, we establish a complete and efficient CLC 2:1 Cl‒/H+ exchange mechanism.
View details for DOI 10.1101/2025.05.08.652968
View details for PubMedID 40655029
View details for PubMedCentralID PMC12248016
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Dynamics and Impacts of Microplastics (MPs) and Nanoplastics (NPs) on Ecosystems and Biogeochemical Processes: The Need for Robust Regulatory Frameworks.
ACS omega
2025; 10 (17): 17051-17069
Abstract
Microplastics (MPs) and nanoplastics (NPs) pose significant threats to aquatic and terrestrial ecosystems, disrupting nutrient cycling, altering soil properties, and affecting microbial communities. MPs and NPs bioaccumulate and contribute to global nutrient and water cycle disruptions, intensifying the impact of climate change. Despite the widespread use of plastics, inadequate plastic waste management leads to persistent environmental pollution. Toxic compounds are transported by MPs and NPs, affecting food chains, nutrient cycles, and overall ecosystem health. MPs impact soil biogeochemistry, microbial activity, and greenhouse gas emissions by altering the nitrogen and carbon cycles. One of the largest gaps in microplastic (MP) research today is the lack of standardized sampling and analytical methods. This lack of standardization significantly complicates the comparison of results across different studies. Multidisciplinary research and strict regulatory measures are needed to address MP pollution. This review highlights the critical need for mitigation methods to maintain ecosystem integrity and suggests standardization of sampling and data analysis. It offers insights into MP distribution, best practices for data analysis, and the impacts and interactions of MPs with biogeochemical processes. The Environmental Protection Agency has identified a critical need to improve the identification of nanoplastics. Particles smaller than 10 μm become increasingly difficult to quantify using standard MP detection practices.
View details for DOI 10.1021/acsomega.5c01175
View details for PubMedID 40352536
View details for PubMedCentralID PMC12060063
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Dynamics and Impacts of Microplastics (MPs) and Nanoplastics (NPs) on Ecosystems and Biogeochemical Processes: The Need for Robust Regulatory Frameworks
ACS OMEGA
2025
View details for DOI 10.1021/acsomega.5c01175
View details for Web of Science ID 001474032300001
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Revolutionizing Postdoctoral Training Using the Social Ecological Model: Insights and Experiences from the Propel Scholars
GEN BIOTECHNOLOGY
2024
View details for DOI 10.1089/genbio.2024.0014
View details for Web of Science ID 001283346900001
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Revolutionizing Postdoctoral Training Using the Social Ecological Model: Insights and Experiences from the Propel Scholars.
GEN biotechnology
2024; 3 (4): 196-206
Abstract
The dissatisfaction within the postdoctoral training phase has led to the drastic reduction in the number of U.S. citizens pursuing postdoctoral positions within the biological and biomedical sciences fields. Even more so, there is an obvious disparity in not only the recruitment but the retention among underrepresented groups to pursue careers as academic scientists. The proposed social-ecological model and National Institute of Health advisory committee suggests reforming the postdoctoral training phase to overcome these downward trends and disparities. Importantly, some programs like the Stanford Propel Postdoctoral Program were integrating this framework and recommendations without knowledge that they would be released 2 years later. The goal of the Propel Program is to provide social, cohort, financial, and institutional support to diverse cohorts of postdoctoral trainee to diversify the professoriate. Within this piece, several of the Propel scholars come together to provide their perspectives on how the Propel Program has benefited their postdoctoral training experience.
View details for DOI 10.1089/genbio.2024.0014
View details for PubMedID 40709103
View details for PubMedCentralID PMC12288851
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New insights into the molecular mechanisms of the coupling of proton and chloride in ClC antiporters
CELL PRESS. 2024: 400A
View details for Web of Science ID 001194120702348
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Potential microbes for environment and agriculture: Bioengineering strategies for a sustainable future
Biotechnology of Emerging Microbes
2024
View details for DOI 10.1016/b978-0-443-15397-6.00001-2
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Persistence, Toxicity, and Strategies for Remediation of Brominated Flame Retardants in Soil and Sedimentation in Aquatic Matrices Under Aerobic and Anaerobic Conditions
Land Remediation and Management: Bioengineering Strategies
2023
View details for DOI 10.1007/978-981-99-4221-3_5
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Antibiotic resistant genes in the environment-exploring surveillance methods and sustainable remediation strategies of antibiotics and ARGs.
Environmental research
2022: 114212
Abstract
Antibiotic Resistant Genes (ARGs) are an emerging environmental health threat due to the potential change in the human microbiome and selection for the emergence of antibiotic resistant bacteria. The rise of antibiotic resistant bacteria has caused a global health burden. The WHO (world health organization) predicts a rise in deaths due to antibiotic resistant infections. Since bacteria can acquire ARGs through horizontal transmission, it is important to assess the dissemination of antibiotic resistant genes from anthropogenic sources. There are several sources of antibiotic resistant bacteria and genes in the environment. These include wastewater treatment plants, landfill leachate, agricultural, animal industrial sources and estuaries. The use of antibiotics is a worldwide practice resulting in the evolution of resistance to antibiotics. Our review provides a more comprehensive look into multiple sources of ARG's and antibiotics rather than one. Moreover, we focus on effective surveillance methods of ARGs and antibiotics and sustainable abiotic and biotic remediation strategies for removal and reduction of antibiotics and ARGs from both terrestrial and aquatic environments. Further, we consider the impact on public health as this problem cannot be addressed without a global transdisciplinary effort.
View details for DOI 10.1016/j.envres.2022.114212
View details for PubMedID 36037921
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Biosurfactant-assisted phytoremediation of potentially toxic elements in soil: Green technology for meeting the United Nations Sustainable Development Goals
PEDOSPHERE
2022; 32 (1): 198-210
View details for DOI 10.1016/S1002-0160(21)60067-X
View details for Web of Science ID 000736927500004
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Ectopic growth of the Chaetothyriales fungal symbiont on <i>Ipomoea carnea</i>
BOTANY
2021; 99 (10): 619-627
View details for DOI 10.1139/cjb-2021-0037
View details for Web of Science ID 000708448400004
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Biosurfactant-Inspired Control of Methicillin-Resistant Staphylococcus aureus (MRSA)
Biosurfactants for a Sustainable Future: Production and Applications in the Environment and Biomedicine
Wiley. 2021
View details for DOI 10.1002/9781119671022.ch14
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Evidence of Calcium Signaling and Modulation of the LmrS Multidrug Resistant Efflux Pump Activity by Ca2 + Ions in S. aureus.
Frontiers in microbiology
2020; 11: 573388
Abstract
Calcium ions (Ca2+) play a pivotal role in eukaryote cell signaling and regulate many physiological functions. Although a similar role for Ca2+ in prokaryotes has been difficult to demonstrate, there is increasing evidence for Ca2+ as a cell regulator in bacteria. The purpose of this study was to investigate Ca2+ signaling and the effect of Ca2+ on the Staphylococcus aureus multidrug resistant efflux pump LmrS. We hypothesized that antibiotics act by increasing Ca2+ concentrations, which in turn enhance the efflux activity of LmrS. These Ca2+ transients were measured by luminometry in response to various antibiotics by using the photoprotein aequorin reconstituted within live bacterial cells. Efflux associated with LmrS was measured by the increase in fluorescence due to the loss of ethidium bromide (EtBr) from both S. aureus cells and from E. coli cells in which the lmrs gene of S. aureus was expressed. We found that addition of antibiotics to cells generated unique cytosolic Ca2+ transients and that addition of CaCl2 to cells enhanced EtBr efflux whereas addition of Ca2+ chelators or efflux pump inhibitors significantly decreased EtBr efflux from cells. We conclude that antibiotics induce a Ca2+ mediated response through transients in cytosolic Ca2+, which then stimulates LmrS efflux pump.
View details for DOI 10.3389/fmicb.2020.573388
View details for PubMedID 33193178
View details for PubMedCentralID PMC7642317
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Biodegradation of bisphenol A by bacterial consortia isolated directly from river sediments
ENVIRONMENTAL TECHNOLOGY & INNOVATION
2019; 14
View details for DOI 10.1016/j.eti.2019.01.008
View details for Web of Science ID 000477670000004
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Mechanistic understanding and future prospect of microbe-enhanced phytoremediation of polycyclic aromatic hydrocarbons in soil
ENVIRONMENTAL TECHNOLOGY & INNOVATION
2019; 13: 318-330
View details for DOI 10.1016/j.eti.2018.12.004
View details for Web of Science ID 000457796000028
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Evidence for nonpathogenic relationships of <i>Alternaria</i> section <i>Undifilum</i> endophytes within three host locoweed plant species
BOTANY
2018; 96 (3): 187-200
View details for DOI 10.1139/cjb-2017-0117
View details for Web of Science ID 000426971600004
https://orcid.org/0000-0003-2516-7432