Article
Pharmacology & Pharmacy
Danijela D. Nikodijevic, Jovana V. Jovankic, Danijela M. Cvetkovic, Marko Z. Andelkovic, Aleksandra G. Nikezic, Milena G. Milutinovic
Summary: The study evaluated the potential antitumor activity of snake venom and L-amino acid oxidase on colorectal cancer cells, showing that snake venom primarily led to necrosis while L-amino acid oxidase induced apoptosis correlated with oxidative imbalances in cancer cells. Additionally, the gene expression profiles and levels of membrane transporters also impacted the sensitivity of treatment across different cell lines. The findings suggest that L-amino acid oxidase could be a promising substance for further research on its antitumor effects, potentially with lower risk of drug resistance in vitro.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jianyi Li, Yuntong Lv, Kunpeng Yan, Fengting Yang, Xuewei Chen, Xiwu Gao, Shuyuan Wen, Hongfei Xu, Yiou Pan, Qingli Shang
Summary: The study revealed that ATP-binding cassette transporters (ABCs) play important roles in cyantraniliprole resistance. Inhibition of ABCs increased the toxicity of cyantraniliprole, while overexpression of ABCs in fruit flies enhanced their tolerance to cyantraniliprole. Suppression of specific ABC transporters increased the sensitivity of cyantraniliprole-resistant strains. These findings provide valuable insights for resistance management strategies.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2022)
Article
Microbiology
Magali Van den Kerkhof, Philippe Leprohon, Dorien Mabille, Sarah Hendrickx, Lindsay B. Tulloch, Richard J. Wall, Susan Wyllie, Eric Chatelain, Charles E. Mowbray, Stephanie Braillard, Marc Ouellette, Louis Maes, Guy Caljon
Summary: Oxaboroles, a novel class of antileishmanial drugs, have not shown readily emergent resistance and hold promise for future treatment. The combination of a genome-wide cosmid library and next-generation sequencing can identify resistance determinants and potential targets.
Article
Agriculture, Multidisciplinary
Yuntong Lv, Kunpeng Yan, Xiwu Gao, Xuewei Chen, Jianyi Li, Yaping Ding, Hang Zhang, Yiou Pan, Qingli Shang
Summary: This study explores the involvement of ATP-binding cassette (ABC) transporters in spirotetramat resistance in cotton aphids. The results show that several ABC transporter genes, including ABCB4, ABCB5, ABCF2, MRP11, and MRP12, are upregulated in the spirotetramat-resistant strains. Functional analysis confirms the contribution of these genes to spirotetramat tolerance.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Analytical
Yanyan Ma, Zhanchen Guo, Chuanwen Fan, Jingran Chen, Shuxin Xu, Zhen Liu
Summary: This study developed aptamers that can target ABCG2 and reverse multidrug resistance, showing great potential in cancer diagnosis and treatment. The aptamers can specifically bind to human colorectal cancer stem cells and effectively reverse drug resistance in liver cancer cells.
ANALYTICAL CHEMISTRY
(2022)
Article
Microbiology
Jan Viglas, Petra Olejnikova
Summary: The ABC transporter superfamily plays a crucial role in transporting various molecules across biological membranes, including antifungal compounds in filamentous fungi. Understanding the physiological substrates and roles of individual subfamilies of ABC transporters in fungi is important for clarifying their significance in clinical and agricultural settings.
MICROBIOLOGICAL RESEARCH
(2021)
Article
Medicine, Research & Experimental
Lara Garcia-Varela, Manuel Rodriguez-Perez, Antia Custodia, Rodrigo Moraga-Amaro, Nicola A. Colabufo, Pablo Aguiar, Tomas Sobrino, Rudi A. J. O. Dierckx, Aren van Waarde, Philip H. Elsinga, Gert Luurtsema
Summary: P-glycoprotein (P-gp) inducer MC111 increases P-gp functionality in the whole brain of rats, potentially offering a treatment option for neurodegenerative diseases.
MOLECULAR PHARMACEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Yuntong Lv, Yiou Pan, Jianyi Li, Yaping Ding, Zihan Yu, Kunpeng Yan, Qingli Shang
Summary: Clarifying the molecular mechanisms of cotton aphid resistance to various insecticides is crucial for safe insecticide application. This study reveals that ABCB5, ABCF2, and MRP12 are negatively regulated by the transcription factor CF2-II, leading to increased resistance to certain insecticides. These findings contribute to a better understanding of the adaptation mechanism of ABC transporters in the context of multi-insecticide resistance.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Plant Sciences
Georgios Sofianos, Anastasios Samaras, Georgios Karaoglanidis
Summary: Botrytis cinerea is a high-risk pathogen for fungicide resistance development. The study found that MLR/MDR strains are present in Greek populations of strawberries, rootstocks, and tomatoes, with notably high frequencies of resistance. The combination of MLR and MDR mutations leads to even higher levels of fungicide resistance.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Pharmacology & Pharmacy
Lena Radtke, Aleksandra Majchrzak-Celinska, Charles Awortwe, Inga Vater, Inga Nagel, Susanne Sebens, Ingolf Cascorbi, Meike Kaehler
Summary: This study demonstrates the significance of ABCB1 in GBM cells, affecting the response to temozolomide and carmustine treatment, while ABCG2 plays a marginal role.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Agronomy
Jinqiong Shan, Xi Sun, Ran Li, Bin Zhu, Pei Liang, Xiwu Gao
Summary: Overexpression of certain genes in the ABCG subfamily is implicated in the resistance of Plutella xylostella to chlorantraniliprole. These findings could provide a foundation for further exploration of the role of ABC transporters in chlorantraniliprole resistance in Plutella xylostella and other insect pests.
PEST MANAGEMENT SCIENCE
(2021)
Review
Pharmacology & Pharmacy
Ragini Amarnani, Amey Revdekar, Bhagyashree Salvi, Pravin Shende
Summary: Some existing therapies are not effective in treating drug-resistant infections due to low drug efficacy, increasing dosage regimes, bacteria mutations, and poor drug properties. Overuse of antibiotics leads to the emergence and spread of resistant microorganisms. Nanocarriers with ABC transporter efflux mechanism can overcome multidrug resistance by interfering with normal cell activity. This review focuses on the novel applications of nanocarriers using the ABC transporter pump to overcome resistance in various organs.
DRUG DISCOVERY TODAY
(2023)
Review
Pharmacology & Pharmacy
Lenka Hruba, Viswanath Das, Marian Hajduch, Petr Dzubak
Summary: Nucleoside-based drugs, widely used in the treatment of various diseases, have been hindered by drug resistance. This review explores the mechanisms of resistance, including changes in membrane transporters, activating kinases, drug elimination strategies, and DNA damage repair mechanisms. The critical analysis in this review points towards novel therapeutic strategies such as targeted therapies, new nucleoside analogs, and synergistic drug combinations to overcome resistance and improve patient outcomes.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dandan Zhang, Minghui Jin, Yanchao Yang, Jianfeng Zhang, Yongbo Yang, Kaiyu Liu, Mario Soberon, Alejandra Bravo, Yutao Xiao, Kongming Wu
Summary: The evolution of resistance in target pests reduces the efficacy of Bacillus thuringiensis Cry toxins in insect-pest control. Mutations in Cadherin (CAD) or ATP-binding cassette (ABC) transporter genes have been linked to Cry resistance in different pests, and there is a synergistic interaction between ABCC2 and CAD in Cry toxicity. Studies on isogenic lines of Helicoverpa armigera showed significantly enhanced Cry1Ac resistance when both HaABCC2 and HaCAD mutations were present, suggesting a synergistic effect between CAD and ABCC2.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Immunology
Armaan A. Akhtar, David P. J. Turner
Summary: Bacterial ABC transporters play a crucial role in virulence and pathogenesis by importing essential molecules and exporting virulent determinants and toxic substances. They also have potential applications in treatments and vaccines.
MICROBIAL PATHOGENESIS
(2022)
Article
Infectious Diseases
Elena Carrara, Alessia Savoldi, Laura J. Piddock, Francois Franceschi, Sally Ellis, Mike Sharland, Adrian John Brink, Patrick N. A. Harris, Gabriel Levy-Hara, Anusha Rohit, Constantinos Tsioutis, Hiba Zayyad, Christian Giske, Margherita Chiamenti, Damiano Bragantini, Elda Righi, Anna Gorska, Evelina Tacconelli
Summary: The optimal treatment for carbapenem-resistant Gram-negative bacteria infections varies globally, with dual combination therapy being the preferred treatment scheme. However, there is disagreement among clinicians regarding the definition of 'combination therapy.'
CLINICAL MICROBIOLOGY AND INFECTION
(2022)
Article
Immunology
Laura J. Piddock, Jean-Pierre Paccaud, Seamus O'Brien, Michelle Childs, Rohit Malpani, Manica Balasegaram
Summary: Antibiotics are crucial for modern medicine, but commercial developers do not see sufficient profitability to address public need. Nonprofit research and development organizations have the potential to collaborate and provide new antibiotics.
CLINICAL INFECTIOUS DISEASES
(2022)
Editorial Material
Infectious Diseases
Laura J. Piddock
Summary: The discovery of antibiotics revolutionized medicine, but now antimicrobial resistance is becoming a greater problem than the development of new antimicrobials. New political and economic models are needed to address this escalating crisis. This article examines the challenges and proposes strategies to overcome them.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Maria Laura Ciusa, Robert L. Marshall, Vito Ricci, Jack W. Stone, Laura J. Piddock
Summary: The study found that inhibiting the AcrB efflux pump in Escherichia coli did not significantly increase the expression of other efflux pump genes, indicating that there is no compensatory mechanism to overcome efflux inhibition.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Chemistry, Medicinal
Gang Wang, Jean-Michel Brunel, Hector Rodriguez-Villalobos, Jean-Michel Bolla, Francoise Van Bambeke
Summary: NV716 can enhance the activity of antibiotics against difficult-to-treat Gram-negative bacteria by interacting with the bacterial outer membrane, resulting in increased accumulation of antibiotics inside bacteria. It can also increase the activity of antibiotics against intracellular infection and biofilms, without toxicity to eukaryotic cells at sub-MIC concentrations.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Infectious Diseases
Angele Modupe Dohou, Valentina Oana Buda, Loconon Achille Yemoa, Severin Anagonou, Francoise Van Bambeke, Thierry Van Hees, Francis Moise Dossou, Olivia Dalleur
Summary: The excessive use and misuse of antibiotics have a significant impact on the global numbers of antibiotic-resistant pathogens and commensal bacteria. In Benin, there are various problems with antibiotic use during caesarean sections, highlighting the need for a national policy to improve antibiotic usage.
Article
Infectious Diseases
Angele Modupe Dohou, Valentina Oana Buda, Severin Anagonou, Francoise Van Bambeke, Thierry Van Hees, Francis Moise Dossou, Olivia Dalleur
Summary: A low adherence to recommendations on antibiotic prophylaxis has been reported worldwide. In Benin, despite the provision of free kits containing necessary supplies and antibiotics for prophylaxis during cesarean sections, the level of antibiotic prophylaxis achievement remains low. A study in three hospitals found that healthcare professionals had limited knowledge and various determinants, such as suboptimal patient health status, low confidence in antibiotics, disagreement with the policy, inappropriate infrastructures and limited financial resources, poor management of the policy at the central level, and patient refusal to buy antibiotics, explain the poor practices. Policymakers must consider these determinants to improve antibiotic prophylaxis and reduce antimicrobial resistance.
Article
Infectious Diseases
Perrin Ngougni Pokem, Xavier Wittebole, Christine Collienne, Hector Rodriguez-Villalobos, Paul M. Tulkens, Laure Elens, Francoise Van Bambeke, Pierre-Francois Laterre
Summary: This study investigated the pharmacokinetics of temocillin in plasma and ascitic fluid, and performed dosing simulations. The current dosing regimen achieved the target concentration in plasma, but not in ascitic fluid. Adjusting the dosing regimen might allow for target concentration attainment in ascitic fluid, but further evaluation is needed for safety and efficacy.
Article
Infectious Diseases
Jessica M. A. Blair, Pauline Siasat, Helen E. McNeil, Abigail Colclough, Vito Ricci, Amelia J. Lawler, Hind Abdalaal, Michelle M. C. Buckner, Alison Baylay, Stephen J. Busby, Laura J. Piddock
Summary: In this study, it was found that EnvR is a potent repressor of acrAB transcription in Salmonella, and can override binding by RamA, thus preventing multidrug resistance to clinically useful drugs. Finding novel tools to increase EnvR expression may form the basis of a new way to prevent or treat multidrug-resistant infections.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Editorial Material
Infectious Diseases
Laura Piddock
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2023)
Correction
Microbiology
Albert Ruiz-Sorribas, Herve Poilvache, Nur Hidayatul Nazirah Kamarudin, Annabel Braem, Francoise Van Bambeke
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Alistair D. Middlemiss, James R. J. Haycocks, Anne M. Stringer, Laura J. V. Piddock, Joseph T. Wade, David C. Grainger
Summary: The transcription factors MarA, SoxS, Rob and RamA control overlapping stress responses in enteric bacteria and their constitutive expression is linked to antibiotic resistance. The study mapped the binding sites of these factors across the Salmonella Typhimurium genome and identified changes in transcription start sites. This information helps disentangle direct and indirect gene regulation effects and deduce promoter architecture within the regulon. The control of csgD, which is involved in biofilm formation, is particularly sensitive to SoxS repression in Salmonella Typhimurium unlike in Escherichia coli where MarA indirectly regulates csgD expression.
Editorial Material
Infectious Diseases
Francoise Van Bambeke, Sebastian Wicha, Paul M. Tulkens, Markus Zeitlinger
Article
Infectious Diseases
Alasdair P. Macgowan, M. L. G. Attwood, Alan R. Noel, R. Barber, Zachary Aron, Timothy J. Opperman, Elizabeth Grimsey, Jack Stone, Vito Ricci, L. J. Piddock
Summary: This study investigated the pharmacodynamic characteristics of efflux pump inhibitors (EPIs) in Escherichia coli through in vitro experiments and gene sequencing. The results showed that the AUC of chlorpromazine and PA beta N was most closely related to the reduction in bacterial load, while the T > threshold of MBX-4191 was the driver for bacterial load reduction. No changes in population profiles were observed with the combination of ciprofloxacin + EPIs, but mutations were detected in gyrA, gyrB, and marR.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Review
Biotechnology & Applied Microbiology
Ursula Theuretzbacher, Benjamin Blasco, Maelle Duffey, Laura J. V. Piddock
Summary: Advances in genomics, systems biology, protein structure determination, and artificial intelligence provide new opportunities for target-based antibacterial drug discovery. Multiple criteria, including target essentiality, conservation, homology with human genes, and drug-like binding potential, need to be considered in selecting a suitable target. Subcellular location and the risk of drug resistance also play important roles in the process. This review highlights promising targets and inhibitors for Gram-negative bacteria and lessons learned from past drug discovery programs.
NATURE REVIEWS DRUG DISCOVERY
(2023)