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131. Targeting the Divergent Roles of STK3 Inhibits Breast Cancer Cell Growth and Opposes Doxorubicin-Induced Cardiotoxicity In Vitro

Title Tesim:
Targeting the Divergent Roles of STK3 Inhibits Breast Cancer Cell Growth and Opposes Doxorubicin-Induced Cardiotoxicity In Vitro
Creator:
Drewry, David H., Nam, Jiung, Macias, Everardo, Loh, Chelsea, and Schirmer, Amelia U.
Date of publication:
2023
Abstract Tesim:
Breast cancer (BCa) is the most prevalent type of cancer in women. Several therapies used in the treatment of breast cancer are associated with clinically important rates of cardiovascular toxicity during or after treatment exposure, including anthracyclines. There is a need for new BCa therapeutics and treatments that mitigate chemotherapy-induced cardiotoxicity in BCa. In this study, we examine the effects of Serine/Threonine Kinase 3 (STK3) inhibition in the context of BCa therapy and cardioprotection from doxorubicin. STK3 (also known as MST2) is a key member of the Hippo Tumor-Suppressor Pathway, which regulates cell growth and proliferation by inhibiting YAP/TAZ co-transcription factors. Canonically, STK3 should restrict BCa growth; however, we observed that STK3 is amplified in BCa and associated with worse patient outcomes, suggesting a noncanonical pro-tumorigenic role. We found BCa cell lines have varying dependence on STK3. SUM52PE cells had the highest expression and dependence on STK3 in genetic and pharmacological assays. MCF-7 and MDA-MB-231 were less sensitive to STK3 targeting in standard proliferation assays, but were STK3 dependent in colony formation and matrigel invasion assays. In contrast, STK3 inhibition mitigated the toxic effects of doxorubicin in H9C2 rat cardiomyocytes by increasing YAP expression. Importantly, STK3 inhibition in BCa cells did not interfere with the therapeutic effects of doxorubicin. Our studies highlight STK3 is a potential molecular target for BCa with dual therapeutic effects: suppression of BCa growth and progression, and chemoprotection in cardiomyocytes.
Resource type:
Article
Affiliation Label Tesim:
Eshelman School of Pharmacy
DOI:
https://doi.org/10.17615/78dv-b312
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/cancers15102817
ISSN:
2072-6694
Journal Issue:
10
Journal Title:
Cancers
Journal Volume:
15
Keyword:
STK3, cardio-oncology, yap, cardiotoxicity, breast cancer, and hippo kinase
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
and Duke University School of Medicine
Page Start:
2817
Person:
Drewry, David H., Nam, Jiung, Macias, Everardo, Loh, Chelsea, and Schirmer, Amelia U.
Rights Statement Label:
In Copyright
Source:
939c353c-79b5-43fe-a925-62da5b36124d

132. Targeting Mitochondrial DNA Transcription by POLRMT Inhibition or Depletion as a Potential Strategy for Cancer Treatment

Title Tesim:
Targeting Mitochondrial DNA Transcription by POLRMT Inhibition or Depletion as a Potential Strategy for Cancer Treatment
Creator:
Graves, Lee M., Fennell, Emily M. J., and Daglish, Sabrina C. D.
Date of publication:
2023
Abstract Tesim:
Transcription of the mitochondrial genome is essential for the maintenance of oxidative phosphorylation (OXPHOS) and other functions directly related to this unique genome. Considerable evidence suggests that mitochondrial transcription is dysregulated in cancer and cancer metastasis and contributes significantly to cancer cell metabolism. Recently, inhibitors of the mitochondrial DNA-dependent RNA polymerase (POLRMT) were identified as potentially attractive new anti-cancer compounds. These molecules (IMT1, IMT1B) inactivate cancer cell metabolism through reduced transcription of mitochondrially-encoded OXPHOS subunits such as ND1-5 (Complex I) and COI-IV (Complex IV). Studies from our lab have discovered small molecule regulators of the mitochondrial matrix caseinolytic protease (ClpP) as probable inhibitors of mitochondrial transcription. These compounds activate ClpP proteolysis and lead to the rapid depletion of POLRMT and other matrix proteins, resulting in inhibition of mitochondrial transcription and growth arrest. Herein we present a comparison of POLRMT inhibition and ClpP activation, both conceptually and experimentally, and evaluate the results of these treatments on mitochondrial transcription, inhibition of OXPHOS, and ultimately cancer cell growth. We discuss the potential for targeting mitochondrial transcription as a cancer cell vulnerability.
Resource type:
Article
Affiliation Label Tesim:
Department of Pharmacology
DOI:
https://doi.org/10.17615/wjtv-6567
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/biomedicines11061598
ISSN:
2227-9059
Journal Issue:
6
Journal Title:
Biomedicines
Journal Volume:
11
Keyword:
ClpP, mitochondrial DNA, mitochondria, oxidative phosphorylation, mitochondrial transcription, mechanism of action, and POLRMT
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
Page Start:
1598
Person:
Graves, Lee M., Fennell, Emily M. J., and Daglish, Sabrina C. D.
Rights Statement Label:
In Copyright
Source:
9db7f2df-b5cb-45c9-93e0-89c191b9fc56

133. Spatiotemporal Evolution of Urban Agglomeration and Its Impact on Landscape Patterns in the Pearl River Delta, China

Title Tesim:
Spatiotemporal Evolution of Urban Agglomeration and Its Impact on Landscape Patterns in the Pearl River Delta, China
Creator:
Meng, Chen, Xiao, Huirong, Haase, Dagmar, Liu, Yuhan, Ouyang, Linke, Zhuang, Minghao, Zhang, Qi, Wu, Hui, Wu, Caiyan, Wu, Jiong, Song, Conghe, and Li, Junxiang
Date of publication:
2023
Abstract Tesim:
An urban agglomeration is the engine of regional and national economic growth, but also causes many ecological and environmental issues that emerge from massive land changes. In this study, the spatiotemporal evolution of an urban agglomeration was quantified and its impacts on the urban and regional landscape patterns were evaluated. It showed that the urbanized land area of the Pearl River Delta Urban Agglomeration (PRDUA) in China nearly quadrupled, having linearly increased from 1819.8 km2 to 7092.2 km2 between 1985 and 2015. The average annual growth rate presented a bimodal wave-like pattern through time, indicating that the PRDUA has witnessed two rounds of the urbanization process. The growth modes (e.g., leapfrog, edge-expansion, infilling) were detected and they exhibited co-existing but alternating dominating patterns during urbanization, demonstrating that the spatiotemporal evolution of the urban development of the PRDUA follows the “spiral diffusion-coalescence” hypothesis. The morphology of the PRDUA presented an alternating dispersal-compact pattern over time. The city-level and regional-level landscape patterns changed synchronously with the spatiotemporal evolution of the PRDUA over time. The urbanization of the PRDUA increased both the complexity and aggregation of the landscape, but also resulted in an increasing fragmentation and decreasing connectivity of the natural landscape in the Pearl River Delta region. These findings are helpful for better understanding how urban agglomerations evolve and in providing insights for regional urban planning and sustainable land management.
Resource type:
Article
Affiliation Label Tesim:
Department of Geography
DOI:
https://doi.org/10.17615/qf4v-jx07
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/rs15102520
ISSN:
2072-4292
Journal Issue:
10
Journal Title:
Remote Sensing
Journal Volume:
15
Keyword:
urban agglomeration, spatiotemporal evolution, PRDUA, urban growth, Pearl River Delta, landscape expansion index, and diffusion and coalescence hypothesis
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
East China Normal University, Shanghai Jiao Tong University, Humboldt-Universität zu Berlin, Shanghai Artificial Intelligence Laboratory, , and Shanghai Investment Consulting Group Ltd.
Page Start:
2520
Person:
Meng, Chen, Xiao, Huirong, Haase, Dagmar, Liu, Yuhan, Ouyang, Linke, Zhuang, Minghao, Zhang, Qi, Wu, Hui, Wu, Caiyan, Wu, Jiong, Song, Conghe, and Li, Junxiang
Publisher:
MDPI
Rights Statement Label:
In Copyright
Source:
517705f6-1549-4126-aceb-00a1f468ee12

134. Should Government Play a Strict or Lenient Role? An Evolutionary Game Analysis of Implementing the Forest Ecological Bank Policy

Title Tesim:
Should Government Play a Strict or Lenient Role? An Evolutionary Game Analysis of Implementing the Forest Ecological Bank Policy
Creator:
Nie, Xin, Li, Weijuan, Yang, Mengshi, Wang, Han, Zang, Ran, and Chen, Zhoupeng
Date of publication:
2023
Abstract Tesim:
As one of the specific practices of natural resource index trading, the forest ecological bank policy (FEB) is essentially a market-based tool. With the deepening of ecological governance, the FEB policy has also become the main method chosen to solve the economic development problems in ecologically rich “low-lying” areas. However, in the process of implementing the FEB policy, the differences in the demands of various stakeholders were found to have led to a complex game phenomenon, resulting in deviations in policy implementation. This study constructs a multiplayer evolutionary game model between local governments and enterprises of different scales and analyzes the evolutionary stabilization strategy (ESS) in the implementation of the FEB policy. The results show that, under different conditions, there are three stabilization strategies in the evolutionary game system, these correspond to F1 (0, 0, 0), F4 (0, 1, 1), and F5 (1, 0, 0), respectively, the implications are that the strict government role with an active regulatory strategy leads to companies of different sizes refusing to participate (i.e., F5) and the lax government role with a negative regulatory strategy leads to companies of different sizes refusing to participate (i.e., F1) or choosing to participate (i.e., F4). Among them, the strict government role stimulates the companies to participate in the FEB policy through the high intensity of government regulation. In addition, as the policy continues to be implemented, the influence of the strict regulation on the “participation” behavior of the companies decreases. Conversely, the lax government role allows the companies to give full play to their autonomy and obtain higher ecological and environmental benefits.
Resource type:
Article
Affiliation Label Tesim:
Department of City and Regional Planning
DOI:
https://doi.org/10.17615/9g9d-ah46
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/f14051002
ISSN:
1999-4907
Journal Issue:
5
Journal Title:
Forests
Journal Volume:
14
Keyword:
natural resource indicator trading, forest ecological bank policy, evolutionary game, and evolutionary stabilization strategy
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
and Guangxi University
Page Start:
1002
Person:
Nie, Xin, Li, Weijuan, Yang, Mengshi, Wang, Han, Zang, Ran, and Chen, Zhoupeng
Publisher:
MDPI
Rights Statement Label:
In Copyright
Source:
c86b7532-3d25-435b-9cb9-56315426efa4

135. RYK Gene Expression Associated with Drug Response Variation of Temozolomide and Clinical Outcomes in Glioma Patients

Title Tesim:
RYK Gene Expression Associated with Drug Response Variation of Temozolomide and Clinical Outcomes in Glioma Patients
Creator:
Havener, Tammy M., Akhtari, Farida S., McLeod, Howard L., Small, George W., Quintanilha, Julia C. F., Wiltshire, Tim, Cipriani, Amber B., Motsinger-Reif, Alison A., Green, Adrian J., Reif, David M., and Gonzalez, Ricardo D.
Date of publication:
2023
Abstract Tesim:
Temozolomide (TMZ) chemotherapy is an important tool in the treatment of glioma brain tumors. However, variable patient response and chemo-resistance remain exceptionally challenging. Our previous genome-wide association study (GWAS) identified a suggestively significant association of SNP rs4470517 in the RYK (receptor-like kinase) gene with TMZ drug response. Functional validation of RYK using lymphocytes and glioma cell lines resulted in gene expression analysis indicating differences in expression status between genotypes of the cell lines and TMZ dose response. We conducted univariate and multivariate Cox regression analyses using publicly available TCGA and GEO datasets to investigate the impact of RYK gene expression status on glioma patient overall (OS) and progression-free survival (PFS). Our results indicated that in IDH mutant gliomas, RYK expression and tumor grade were significant predictors of survival. In IDH wildtype glioblastomas (GBM), MGMT status was the only significant predictor. Despite this result, we revealed a potential benefit of RYK expression in IDH wildtype GBM patients. We found that a combination of RYK expression and MGMT status could serve as an additional biomarker for improved survival. Overall, our findings suggest that RYK expression may serve as an important prognostic or predictor of TMZ response and survival for glioma patients.
Resource type:
Article
Affiliation Label Tesim:
Division of Chemical Biology and Medicinal Chemistry and Division of Pharmacotherapy and Experimental Therapeutics
DOI:
https://doi.org/10.17615/0f02-sf66
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/ph16050726
ISSN:
1424-8247
Journal Issue:
5
Journal Title:
Pharmaceuticals
Journal Volume:
16
Keyword:
gene expression, chemotherapy, temozolomide, <i>RYK</i>, GWAS, glioma, pharmacogenomics, sensitivity, drug response, overexpression, knockdown, and resistance
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
, National Institute of Environmental Health Sciences, Utah Tech University, Foundation Medicine, and North Carolina State University
Page Start:
726
Person:
Havener, Tammy M., Akhtari, Farida S., McLeod, Howard L., Small, George W., Quintanilha, Julia C. F., Wiltshire, Tim, Cipriani, Amber B., Motsinger-Reif, Alison A., Green, Adrian J., Reif, David M., and Gonzalez, Ricardo D.
Publisher:
MDPI
Rights Statement Label:
In Copyright
Source:
3f4c62a3-be3f-4556-80cc-df6b833d7b17

136. Reuse of Treated Wastewater: Drivers, Regulations, Technologies, Case Studies, and Greater Chicago Area Experiences

Title Tesim:
Reuse of Treated Wastewater: Drivers, Regulations, Technologies, Case Studies, and Greater Chicago Area Experiences
Creator:
Reddy, K.R., Wilson, M.D., Kandou, V., Nelson, B., Havrelock, R., Trujillo, C., El-Khattabi, A.R., and Cordova, T.
Date of publication:
2023
Abstract Tesim:
Water reuse is a practical solution to augment water supplies in areas where water resources are increasingly scarce. Water reuse technology is versatile and can be used to alleviate the different causes of water scarcity, such as groundwater depletion or increased availability of brackish water. Treatment technologies can be tailored specifically to the end use of recycled water, focusing on these drivers that are region-specific, for a more cost-effective treatment system. This is called a “Fit-for-Purpose” strategy that is commonly implemented in any water reuse project. However, implementing water reuse can be challenging due to infrastructural requirements, economic issues, and social acceptance. To help navigate these challenges, this article provides a comprehensive review of water reuse cases and presents guidelines that can act as a reference framework for future water reuse projects. This article also makes the case for implementing water reuse in the Greater Chicago area as a means of alleviating pressure on withdrawals from Lake Michigan.
Resource type:
Article
Affiliation Label Tesim:
University of North Carolina at Chapel Hill
DOI:
https://doi.org/10.17615/4k8j-tf90
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/su15097495
ISSN:
2071-1050
Journal Issue:
9
Journal Title:
Sustainability (Switzerland)
Journal Volume:
15
Keyword:
water reuse, regulations, wastewater treatment, sustainability, water infrastructure, and water recycling
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
University of Illinois Chicago and
Person:
Reddy, K.R., Wilson, M.D., Kandou, V., Nelson, B., Havrelock, R., Trujillo, C., El-Khattabi, A.R., and Cordova, T.
Publisher:
MDPI
Rights Statement Label:
In Copyright
Source:
f14767fe-bc34-4bc5-98ea-03e1e2557ba3

137. Results from Two HPV-Based Cervical Cancer Screening-Family Planning Integration Models in Malawi: A Cluster Randomized Trial

Title Tesim:
Results from Two HPV-Based Cervical Cancer Screening-Family Planning Integration Models in Malawi: A Cluster Randomized Trial
Creator:
Mhango, Eneli, Mbendera, Jacqueline, Gadama, Luis, Smith, Jennifer S., Lee, Fan, Gardner, Leah, Mkochi, Tawonga, Magongwa, Irene, Tang, Jennifer H., Mwandira, Eunice, Schouten, Erik, Mhango, Patani, Msowoya, Lizzie, Chagomerana, Maganizo B., Ghambi, Kachengwa, and Chinula, Lameck
Date of publication:
2023
Abstract Tesim:
We conducted a cluster randomized trial of two models for integrating HPV self-collection into family-planning (FP) services at 16 health facilities in Malawi between March 2020–December 2021. Model 1 involved providing only clinic-based HPV self-collection, whereas Model 2 included both clinic-based and community-based HPV self-collection. An endline household survey was performed in sampled villages and households between October-December 2021 in the catchment areas of the health facilities. We analyzed 7664 surveys from 400 villages. Participants from Model 2 areas were more likely to have ever undergone cervical cancer screening (CCS) than participants from Model 1 areas, after adjusting for district, facility location (urban versus rural), and facility size (hospital versus health center) (adjusted odds ratio = 1.73; 95% CI: 1.29, 2.33). Among participants who had ever undergone CCS, participants from Model 2 were more likely to report having undergone HPV self-collection than participants from Model 1 (50.5% versus 22.8%, p = 0.023). Participants from Model 2 were more likely to be using modern FP (adjusted odds ratio = 1.01; 95% CI: 1.41, 1.98) than Model 1 participants. The integration of FP and HPV self-collection in both the clinic and community increases CCS and modern FP uptake more than integration at the clinic-level alone.
Resource type:
Article
Affiliation Label Tesim:
UNC Project-Malawi, Department of Medicine, Department of Epidemiology, and Department of Obstetrics and Gynecology
DOI:
https://doi.org/10.17615/fzr3-fn04
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/cancers15102797
ISSN:
2072-6694
Journal Issue:
10
Journal Title:
Cancers
Journal Volume:
15
Keyword:
family planning, HPV self-collection, and cervical cancer
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
and Kamuzu University of Health Sciences
Page Start:
2797
Person:
Mhango, Eneli, Mbendera, Jacqueline, Gadama, Luis, Smith, Jennifer S., Lee, Fan, Gardner, Leah, Mkochi, Tawonga, Magongwa, Irene, Tang, Jennifer H., Mwandira, Eunice, Schouten, Erik, Mhango, Patani, Msowoya, Lizzie, Chagomerana, Maganizo B., Ghambi, Kachengwa, and Chinula, Lameck
Rights Statement Label:
In Copyright
Source:
804cf4d8-e301-4d7c-a6fa-6b23eb49995c

138. Pleural Fluid Resolution Is Associated with Improved Survival in Patients with Malignant Pleural Effusion

Title Tesim:
Pleural Fluid Resolution Is Associated with Improved Survival in Patients with Malignant Pleural Effusion
Creator:
Ghosh, Sohini, Ceppe, Agathe, Wright, Amber, MacRosty, Christina R., Akulian, Jason A., and Burks, A. Cole
Date of publication:
2023
Abstract Tesim:
Malignant pleural effusion is associated with a poor prognosis and, while risk stratification models exist, prior studies have not evaluated pleural fluid resolution and its association with survival. We performed a retrospective review of patients diagnosed with malignant pleural effusion between 2013 and 2017, evaluating patient demographics, pleural fluid and serum composition, and procedural and treatment data using Cox regression analysis to evaluate associations with survival. In total, 123 patients were included in the study, with median survival from diagnosis being 4.8 months. Resolution of malignant pleural fluid was associated with a significant survival benefit, even when accounting for factors such as placement of an indwelling pleural catheter, anti-cancer therapy, pleural fluid cytology, cancer pheno/genotypes, and pleural fluid characteristics. Elevated fluid protein, placement of an indwelling pleural catheter, and treatment with targeted or hormone therapies were associated with pleural fluid resolution. We conclude that the resolution of pleural fluid accumulation in patients with malignant pleural effusion is associated with a survival benefit possibility representing a surrogate marker for treatment of the underlying metastatic cancer. These findings support the need to better understand the mechanism of fluid resolution in patients with malignant pleural effusion as well as the tumor–immune interplay occurring with the malignant pleural space.
Resource type:
Article
Affiliation Label Tesim:
Department of Medicine and Division of Pulmonary Diseases and Critical Care Medicine
DOI:
https://doi.org/10.17615/anja-cv33
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/life13051163
ISSN:
2075-1729
Journal Issue:
5
Journal Title:
Life
Journal Volume:
13
Keyword:
lymphoma, malignant pleural effusion, indwelling pleural catheter, spontaneous pleurodesis, pleural disease, resolution of pleural effusion, breast cancer, and lung cancer
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
Allegheny Health Network and
Page Start:
1163
Person:
Ghosh, Sohini, Ceppe, Agathe, Wright, Amber, MacRosty, Christina R., Akulian, Jason A., and Burks, A. Cole
Publisher:
MDPI
Rights Statement Label:
In Copyright
Source:
b99d7378-ba10-4da3-b384-d95addf6e33a

139. MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients

Title Tesim:
MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients
Creator:
Small, George W., Akhtari, Farida S., Gonzalez, Ricardo D., Reif, David M., Havener, Tammy M., Quintanilha, Julia C. F., Motsinger-Reif, Alison A., Green, Adrian J., Wiltshire, Tim, and McLeod, Howard L.
Date of publication:
2023
Abstract Tesim:
Oxaliplatin (OXAL) is a commonly used chemotherapy for treating colorectal cancer (CRC). A recent genome wide association study (GWAS) showed that a genetic variant (rs11006706) in the lncRNA gene MKX-AS1 and partnered sense gene MKX could impact the response of genetically varied cell lines to OXAL treatment. This study found that the expression levels of MKX-AS1 and MKX in lymphocytes (LCLs) and CRC cell lines differed between the rs11006706 genotypes, indicating that this gene pair could play a role in OXAL response. Further analysis of patient survival data from the Cancer Genome Atlas (TCGA) and other sources showed that patients with high MKX-AS1 expression status had significantly worse overall survival (HR = 3.2; 95%CI = (1.17–9); p = 0.024) compared to cases with low MKX-AS1 expression status. Alternatively, high MKX expression status had significantly better overall survival (HR = 0.22; 95%CI = (0.07–0.7); p = 0.01) compared to cases with low MKX expression status. These results suggest an association between MKX-AS1 and MKX expression status that could be useful as a prognostic marker of response to OXAL and potential patient outcomes in CRC.
Resource type:
Article
Affiliation Label Tesim:
Division of Pharmacotherapy and Experimental Therapeutics and Division of Chemical Biology and Medicinal Chemistry
DOI:
https://doi.org/10.17615/26n5-qr83
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/ph16050757
ISSN:
1424-8247
Journal Issue:
5
Journal Title:
Pharmaceuticals
Journal Volume:
16
Keyword:
antisense, oxaliplatin, lncRNA’s, pharmacogenomics, precision medicine, and colorectal cancer
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
, National Institute of Environmental Health Sciences, Foundation Medicine, North Carolina State University, and Utah Tech University
Page Start:
757
Person:
Small, George W., Akhtari, Farida S., Gonzalez, Ricardo D., Reif, David M., Havener, Tammy M., Quintanilha, Julia C. F., Motsinger-Reif, Alison A., Green, Adrian J., Wiltshire, Tim, and McLeod, Howard L.
Publisher:
MDPI
Rights Statement Label:
In Copyright
Source:
bd4fef73-a48d-475b-9a5c-a65b0c7fa681

140. Hydrogen Peroxide, Povidone-Iodine and Chlorhexidine Fail to Eradicate Staphylococcus aureus Biofilm from Infected Implant Materials

Title Tesim:
Hydrogen Peroxide, Povidone-Iodine and Chlorhexidine Fail to Eradicate Staphylococcus aureus Biofilm from Infected Implant Materials
Creator:
Koch, John A., Conlon, Brian P., Brothers, Kimberly M., Gilbertie, Jessica, Urish, Kenneth L., Gish, Charles G., Byrapogu, Venkata K. C., Parker, Dana M., Li, William, and Rowe, Sarah E.
Date of publication:
2023
Abstract Tesim:
Hydrogen peroxide, povidone-iodine, and chlorhexidine are antiseptics that are commonly added to irrigants to either prevent or treat infection. There are little clinical data available that demonstrate efficacy of adding antiseptics to irrigants in the treatment of periprosthetic joint infection after biofilm establishment. The objective of the study was to assess the bactericidal activity of the antiseptics on S. aureus planktonic and biofilm. For planktonic irrigation, S. aureus was exposed to different concentrations of antiseptics. S. aureus biofilm was developed by submerging a Kirschner wire into normalized bacteria and allowing it to grow for forty-eight hours. The Kirschner wire was then treated with irrigation solutions and plated for CFU analysis. Hydrogen peroxide, povidone-iodine, and chlorhexidine were bactericidal against planktonic bacteria with over a 3 log reduction (p < 0.0001). Unlike cefazolin, the antiseptics were not bactericidal (less than 3 log reduction) against biofilm bacteria but did have a statistical reduction in biofilm as compared to the initial time point (p < 0.0001). As compared to cefazolin treatment alone, the addition of hydrogen peroxide or povidone-iodine to cefazolin treatment only additionally reduced the biofilm burden by less than 1 log. The antiseptics demonstrated bactericidal properties with planktonic S. aureus; however, when used to irrigate S. aureus biofilms, these antiseptics were unable to decrease biofilm mass below a 3 log reduction, suggesting that S. aureus biofilm has a tolerance to antiseptics. This information should be considered when considering antibiotic tolerance in established S. aureus biofilm treatment.
Resource type:
Article
Affiliation Label Tesim:
Department of Microbiology and Immunology
DOI:
https://doi.org/10.17615/wy7m-gn18
Edition:
Publisher
Identifier:
https://dx.doi.org/10.3390/life13061230
ISSN:
2075-1729
Journal Issue:
6
Journal Title:
Life
Journal Volume:
13
Keyword:
periprosthetic joint infection, biofilm, surgical infection, oxidative stress, and antibiotic tolerance
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
University of Pittsburgh, , and Edward Via College of Osteopathic Medicine
Page Start:
1230
Person:
Koch, John A., Conlon, Brian P., Brothers, Kimberly M., Gilbertie, Jessica, Urish, Kenneth L., Gish, Charles G., Byrapogu, Venkata K. C., Parker, Dana M., Li, William, and Rowe, Sarah E.
Publisher:
MDPI
Rights Statement Label:
In Copyright
Source:
3afcac57-ec54-41d9-a694-f3bfcc621a81