Review
Biochemistry & Molecular Biology
Narakorn Khunweeraphong, Karl Kuchler
Summary: Multidrug resistance can be a major issue in cancer treatment and microbial infections, with dysregulated overexpression of ATP-binding cassette transporter members being linked to this phenomenon. High-resolution atomic structures from X-ray crystallography or cryo-EM are helping to improve understanding of the mechanisms and dynamics driving these transporters, offering new perspectives for therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Adrian Perez-Ramos, Rabia Ladjouzi, Marius Mihasan, Radja Teiar, Abdellah Benachour, Djamel Drider
Summary: Enterocin DD14 (EntDD14) is a leaderless bacteriocin with activity against Gram-positive bacteria. The ABC transporter DdGHIJ is involved in EntDD14 export and resistance. The primary transporters DdE and DdF are essential for the externalization of EntDD14.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Microbiology
Oliver Goldbeck, Dominik Weixler, Bernhard J. Eikmanns, Christian U. Riedel
Summary: Post-translationally modified, (methyl-)lanthionine-containing peptides produced by Gram-positive bacteria, known as lantibiotics, show potent activity against various bacterial pathogens, including multidrug-resistant strains. The genus Corynebacterium presents widespread lantibiotic resistance traits, such as cell envelope modifications, ABC-transporters, and peptidases. Identification of conserved lantibiotic resistance operons in Corynebacterium highlights potential targets for further research on lantibiotic resistance mechanisms.
Article
Biochemistry & Molecular Biology
Gao-Jie Ye, Chao-Yun Cai, Zhuo-Xun Wu, Qiu-Xu Teng, Jing-Quan Wang, Zhe-Sheng Chen, Bo Wang
Summary: Three series of phenylurea indole derivatives were synthesized with potent inhibitory activities on ABCG2. Four phenylurea indole derivatives with extended 7C system showed the most potent ABCG2 inhibition and no inhibition on ABCB1. Further investigation on two compounds revealed that they increased the accumulation of mitoxantrone in ABCG2-overexpressing cells and stimulated the ATP hydrolysis of ABCG2 transporter.
BIOORGANIC CHEMISTRY
(2023)
Article
Oncology
Lucia Pavlikova, Mario Seres, Albert Breier, Zdena Sulova
Summary: This paper provides an overview of the possible role of miRNAs in the molecular mechanisms that lead to multidrug resistance (MDR). miRNAs regulate post-transcriptional processes in the proteosynthetic pathway and may serve as specific effectors or interesting targets for cancer therapy.
Article
Biochemistry & Molecular Biology
Chao-Yun Cai, Qiu-Xu Teng, Megumi Murakami, Suresh V. Ambudkar, Zhe-Sheng Chen, Vijaya L. Korlipara
Summary: A series of 22 quinazolinamine derivatives with potent inhibitory activities on BCRP and P-gp were synthesized. Compound 22 was identified as a dual BCRP and P-gp inhibitor, while compound 33 showed BCRP inhibitory activity. These compounds changed the localization of BCRP and P-gp, inhibiting the efflux of anticancer drugs by the two ABC transporters. Compounds 22 and 33 also stimulated ATP hydrolysis, increasing the accumulation of mitoxantrone in BCRP-overexpressing cells.
Article
Oncology
Raul Munoz Velasco, Paula Jimenez Sanchez, Ana Garcia Garcia, Raquel Blanco Martinez-Illescas, Angela Pastor Senovilla, Marian Lozano Yague, Alfonsina Trento, Rosa Maria Garcia-Martin, Diego Navarro, Bruno Sainz Jr, Jose Luis Rodriguez Peralto, Victor Javier Sanchez-Arevalo Lobo
Summary: This study explores the role of the chromatin remodeler BPTF in pancreatic ductal adenocarcinoma (PDA). The findings suggest that reducing BPTF levels can inhibit cell proliferation and migration in PDA, as well as enhance the therapeutic effect of gemcitabine. The study also reveals that BPTF is required for c-MYC recruitment to the promoter of ABC-transporters, which affects gemcitabine accumulation in tumor cells and DNA damage.
Article
Oncology
Maciej Sobczak, Magdalena Strachowska, Karolina Gronkowska, Agnieszka Robaszkiewicz
Summary: In this research, the CoREST complex is identified as a key factor that controls the expression of ABC transporters in cisplatin-treated cancer cells, preventing multidrug resistance. The CoREST complex occupancy at gene promoters suppresses the EP300-dependent increase in ABCC transcription induced by cisplatin and gene overexpression in cisplatin-resistant phenotypes. The EP300-mediated activation of ABCC10 in response to cisplatin is only possible in the presence of p53.
Review
Food Science & Technology
Yanlong Cui, Lingli Luo, Xin Wang, Yingying Lu, Yanglei Yi, Yuanyuan Shan, Bianfang Liu, Yuan Zhou, Xin Lu
Summary: Bacteriocins are low-molecular-weight ribosomal peptides or proteins synthesized by bacteria, known for their antibacterial properties. They can be purified and identified for application in food systems, showing potential for food preservation.
COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY
(2021)
Article
Biology
Qian Li, Ruben Cebrian, Manuel Montalban-Lopez, Huan Ren, Weihui Wu, Oscar P. Kuipers
Summary: Li, Cebrian et al. demonstrate that a combination of peptide D-11 and vancomycin shows potent antimicrobial activity against a panel of Gram-negative pathogens without apparent toxicity. They also find that this combination effectively clears Pseudomonas aeruginosa in mice, providing a potential antimicrobial therapy for humans.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Irina S. Panina, Sergey V. Balandin, Andrey V. Tsarev, Anton O. Chugunov, Andrey A. Tagaev, Ekaterina I. Finkina, Daria V. Antoshina, Elvira V. Sheremeteva, Alexander S. Paramonov, Jasmin Rickmeyer, Gabriele Bierbaum, Roman G. Efremov, Zakhar O. Shenkarev, Tatiana V. Ovchinnikova
Summary: To date, several lantibiotics have been found to target lipid II, a peptidoglycan precursor in bacterial cytoplasmic membrane. The alpha-component of lichenicidin, a two-component lantibiotic, contains potential lipid II binding sites. NMR spectroscopy and MD simulations provided evidence that the C-terminal domain of lichenicidin interacts with lipid II. The contact area of lipid II includes pyrophosphate, disaccharide residues, and bactoprenol's first isoprene units.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Yuchen Zhang, Cheukfai Li, Chenglai Xia, Keneth Kin Wah To, Zhixing Guo, Chongyang Ren, Lingzhu Wen, Fang Wang, Liwu Fu, Ning Liao
Summary: The study showed that MRTX849 can effectively overcome multidrug resistance by attenuating ABCB1 efflux activity in drug-resistant cancer cells, enhancing the anticancer efficacy of drugs in ABC1-overexpressing cells.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Infectious Diseases
Levi A. C. Branco, Pedro F. N. Souza, Nilton A. S. Neto, Tawanny K. B. Aguiar, Ayrles F. B. Silva, Romulo F. Carneiro, Celso S. Nagano, Felipe P. Mesquita, Luina B. Lima, Cleverson D. T. Freitas
Summary: Fluorescence microscopy and proteomic analysis revealed that Mo-CBP3-PepI alters cell membrane permeability, induces ROS overproduction, and affects protein profile of K. pneumoniae cells. The proteomic analysis also highlighted changes in essential metabolic pathways. Mo-CBP3-PepI has potential as an alternative molecule to combat K. pneumoniae infections.
Article
Toxicology
Alicja Zajdel, Joanna Nycz, Adam Wilczok
Summary: Lapatinib can reverse chemoresistance of breast cancer cells to paclitaxel, enhancing its anticancer activity, and thus may have potential benefits in the treatment of HER2-negative breast cancer.
TOXICOLOGY IN VITRO
(2021)
Review
Plant Sciences
Katharina Graefe, Lutz Schmitt
Summary: ABC transporters are widely present in plants and play important roles in various physiological processes, including pathogen response, diffusion barrier formation, and phytohormone transport. While the functions of ABCG transporters are diverse, the specific transported substrates remain largely unknown for most of the proteins.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Review
Chemistry, Multidisciplinary
Tim Kroll, Martin Prescher, Sander H. J. Smits, Lutz Schmitt
Summary: The liver is crucial for metabolism and membrane transport proteins, especially ATP binding cassette (ABC) transporters, play a key role in signal transduction within liver cells. These transporters are essential for various functions in the liver, such as bile formation and xenobiotic export. The study of hepatobiliary ABC transporters has rapidly expanded in recent years and holds potential for new avenues in liver membrane transporter research.
Article
Biochemistry & Molecular Biology
Marcel Lagedroste, Sander H. J. Smits, Lutz Schmitt
Summary: Lanthipeptides are ribosomally synthesized and posttranslationally modified peptides, consisting of a leader peptide and a core peptide. The leader peptide is essential for enzyme recognition and secretion, while the core peptide is the target site for posttranslational modifications. Studying model lanthipeptides like nisin provides insights into their modification and secretion processes.
Review
Biochemistry & Molecular Biology
Christoph G. W. Gertzen, Holger Gohlke, Dieter Haeussinger, Diran Herebian, Verena Keitel, Ralf Kubitz, Ertan Mayatepek, Lutz Schmitt
Summary: Bile acids play a vital role in the liver and are a complex biological component regulated by different levels and receptors. Hereditary disorders of these proteins can lead to various liver diseases. Recent research focuses on the molecular mechanisms of bile acid signaling and transport.
BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Dmitry Ghilarov, Satomi Inaba-Inoue, Piotr Stepien, Feng Qu, Elizabeth Michalczyk, Zuzanna Pakosz, Norimichi Nomura, Satoshi Ogasawara, Graham Charles Walker, Sylvie Rebuffat, So Iwata, Jonathan Gardiner Heddle, Konstantinos Beis
Summary: Antibiotic metabolites and antimicrobial peptides play a key role in bacterial competition by entering cells through hijacking membrane proteins. The newly discovered SbmA-like peptide transporters provide insight into the molecular mechanism of peptide uptake, potentially leading to the development of targeted therapeutics.
Article
Biotechnology & Applied Microbiology
Tobias Beer, Sebastian Haensch, Klaus Pfeffer, Sander H. J. Smits, Stefanie Weidtkamp-Peters, Lutz Schmitt
Summary: Secretion systems play a vital role in Gram-negative bacteria by allowing communication with the outside world. This study focused on the hemolysin A (HlyA) type I secretion system (T1SS) in Escherichia coli and analyzed its localization and clustering. The results showed that the amount of ToIC, a component of the T1SS, was not affected by overexpression of the HlyBD complex. Superresolution microscopy revealed that the HlyA T1SS did not exhibit polarization and the size of T1SS clusters did not correlate with outer membrane islands.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zohreh N. Pourhassan, Haiyang Cui, Sakshi Khosa, Mehdi D. Davari, Karl-Erich Jaeger, Sander H. J. Smits, Ulrich Schwaneberg, Lutz Schmitt
Summary: In this study, the secretion efficiency of the hemolysin T1SS of Escherichia coli was optimized. Mutations in the hemolysin enhancer fragment resulted in increased secretion levels. Additionally, the inclusion of a native terminator region further enhanced secretion levels.
Article
Biochemistry & Molecular Biology
Stefanie L. Raschka, Andrzej Harris, Ben F. Luisi, Lutz Schmitt
Summary: This article introduces the role of ABC transporters in fungal antibiotic resistance and discusses the new mechanisms revealed in Pdr5 transporter studies using electron cryo-microscopy structures and machine learning techniques.
Article
Genetics & Heredity
Senthil-Kumar Devan, Stephan Schott-Verdugo, Kira Muentjes, Lilli Bismar, Jens Reiners, Eymen P. Hachani, Lutz P. Schmitt, Astrid P. Hoeppner, Sander H. J. P. Smits, Holger P. Gohlke, Michael P. Feldbruegge
Summary: The transport and translation of mRNAs at specific subcellular sites can achieve spatiotemporal expression. Recent studies have identified microtubule-dependent co-transport on shuttling endosomes as a novel mechanism mediating mRNA trafficking. However, the mechanistic understanding of how RNA-binding proteins are connected to endosomes is still lacking. In this study, a flexible MLLE domain platform within the RNA-binding protein Rrm4 of Ustilago maydis was found to be crucial for endosomal attachment.
Article
Multidisciplinary Sciences
Joshua L. C. Wong, Sophia David, Julia Sanchez-Garrido, Jia Z. Woo, Wen Wen Low, Fabio Morecchiato, Tommaso Giani, Gian Maria Rossolini, Konstantinos Beis, Stephen J. Brett, Abigail Clements, David M. Aanensen, Silvi Rouskin, Gad Frankel
Summary: This study investigates the impact of mutations in OmpK36 on carbapenem resistance in Klebsiella pneumoniae. The researchers found that a recurrent 25c > t transition in ompK36 increases resistance by reducing the expression of OmpK36 in the outer membrane. This mutation attenuates the bacteria in a mouse pneumonia model but leads to treatment failure in the context of carbapenem therapy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Cedric Orelle, Lutz Schmitt, Jean-Michel Jault
Summary: Microorganisms rely on ATP-binding cassette (ABC) transporters, which are membrane proteins, to exchange with their environment for nutrients and remove toxic compounds. While these transporters play a protective role in organisms by expelling unrelated compounds, they can also contribute to resistance to therapeutic treatments. Interestingly, some multidrug ABC transporters exhibit high levels of ATPase activity even without substrates. This inherent activity allows them to efficiently transport drugs before they penetrate into the cell.
TRENDS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Athanasios Papadopoulos, Max Busch, Jens Reiners, Eymen Hachani, Miriam Baeumers, Julia Berger, Lutz Schmitt, Karl-Erich Jaeger, Filip Kovacic, Sander H. J. Smits, Alexej Kedrov
Summary: The periplasmic chaperone Skp of P. aeruginosa plays a crucial role in the maturation and secretion pathway of lipase, preventing misfolding and stabilizing the enzyme. It binds to the lipase via two different modes, maintaining stability through hydrophobic interactions.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Feby M. Chacko, Lutz Schmitt
Summary: The RTX protein family is a group of exoproteins secreted by the Type 1 secretion system (T1SS) of certain Gram-negative bacteria. It is characterized by a nonapeptide sequence (GGxGxDxUx) at the C-terminus. The RTX domain binds to calcium ions in the extracellular medium, leading to proper protein folding. The secreted protein then interacts with the host cell membrane, forming pores and causing cell lysis. This review summarizes the different pathways of RTX toxins' interaction with host cell membrane and discusses the reasons for their specific or nonspecific activity towards different host cell types.
BIOLOGICAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Zohreh N. Pourhassan, Haiyang Cui, Neele Muckhoff, Mehdi D. Davari, Sander H. J. Smits, Ulrich Schwaneberg, Lutz Schmitt
Summary: Protein secretion is advantageous for recombinant protein production. Type 1 secretion systems (T1SS) have a simple architecture and are attractive for biotechnological applications. The hemolysin A type 1 secretion system (HlyA T1SS) from Escherichia coli has been used for secretion of heterologous proteins, but its commercial utility is limited by low secretion titers. To improve this, we engineered the inner membrane complex of the system using KnowVolution strategy, resulting in a novel HlyB variant with improved secretion for two hydrolases.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maryna Loewe, Sebastian Haensch, Eymen Hachani, Lutz Schmitt, Stefanie Weidtkamp-Peters, Alexej Kedrov
Summary: Biochemical processes in crowded cellular environments, such as membranes, are affected by macromolecular crowding. Researchers developed a fluorescence-based sensor to quantify macromolecular crowding at membrane interfaces, and validated its dynamics in Escherichia coli inner membrane vesicles.
