Article
Cell Biology
Angela Merida-Floriano, Will P. M. Rowe, Josep Casadesus
Summary: A bioinformatic search and transcriptomic analysis revealed 48 members of the SOS regulon in Salmonella enterica serovar Typhimurium genome, with heterogeneous expression forming SOSOFF and SOSON subpopulations. The nature and concentration of DNA damaging agents, as well as exposure time, are major factors influencing population structure during SOS induction. Analogies can be drawn between SOS response and other bacterial stress responses generating phenotypic cell variants.
Article
Microbiology
Kathryn J. Stratton, Matthew J. Bush, Govind Chandra, Clare E. M. Stevenson, Kim C. Findlay, Susan Schlimpert
Summary: DNA damage triggers the SOS response in bacteria, and the number of genes regulated by LexA varies between different organisms. This study demonstrates the importance of RecA and LexA for the survival and normal development of Streptomyces venezuelae during DNA-damaging conditions. Through transcriptional profiling and ChIP-seq analysis, the LexA regulon and core DNA damage repair genes were identified in response to treatment with mitomycin C.
JOURNAL OF BACTERIOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Edwin Chen, Matthew J. Culyba
Summary: Researchers have discovered nanobodies that can inhibit the SOS response of Escherichia coli by targeting the LexA repressor-protease. The high-resolution structures of the LexA-nanobody complexes reveal that they function by stabilizing LexA in its inactive conformation and preventing co-proteolysis by RecA*.
Article
Chemistry, Medicinal
Ana Victoria Cheng Jaramillo, Michael B. Cory, Allen Li, Rahul M. Kohli, William M. Wuest
Summary: Resistant and tolerant bacterial infections have significant impact on healthcare expenses and human lives. Current antibiotic research focuses less on the resistance and tolerance in bacterial populations. This study targeted the bacterial SOS response and developed small molecule inhibitors to prevent the deployment of resistance and tolerance mechanisms such as biofilm formation, horizontal gene transfer, and DNA repair.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Deborah Cook, Jordan Carrington, Kevin Johnson, Janelle Hare
Summary: The multidrug-resistant pathogen Acinetobacter baumannii controls its SOS mutagenesis genes using a unique combination of the UmuDAb repressor and the DdrR protein. While there is evidence of interaction between DdrR hybrid proteins, there is no physical interaction observed between UmuDAb and DdrR, suggesting a different mechanism of coregulation. The homodimerization of UmuDAb provides insight into a LexA-independent, coregulatory process in controlling mutagenic DNA damage response.
CANADIAN JOURNAL OF MICROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Duo-hong Sheng, Ye Wang, Shu-ge Wu, Rui-qin Duan, Yue-zhong Li
Summary: UV radiation induces the upregulation of 651 genes in M. xanthus, including typical SOS genes, mostly enriched in pathways of DNA replication and repair, secondary metabolism, and signal transduction. Deletion of lexA delays growth in M. xanthus, but UV-induced expression of SOS genes in the lexA mutant is similar to that in the wild-type strain.
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Microbiology
Wei-Lin Su, Marie-Florence Bredeche, Sara Dion, Julie Dauverd, Benedicte Condamine, Arnaud Gutierrez, Erick Denamur, Ivan Matic
Summary: Toxin-antitoxin systems play a crucial role in the survival and maintenance of bacteria, particularly when they face genotoxic stress and chemical competition. TisB, through inducing a drop in the proton motive force, has complex effects in the regulation of cytotoxicity by different antibiotics.
Article
Biotechnology & Applied Microbiology
Yongzhong Lu, Linyue Cheng
Summary: LexA-binding sites and LexA regulons were predicted in 23 Proteus genomes, showing a wide distribution of the SOS system in this genus; proteomic and RT-qPCR analyses revealed that under iron deficiency, the members of LexA regulon were regulated in different ways, suggesting a precise regulation mechanism of SOS response.
Article
Microbiology
Anja Pavlin, Gregor Bajc, Nadine Fornelos, Douglas F. Browning, Matej Butala
Summary: We previously identified a 50-residue bacteriophage protein, gp7, which interacts with and modulates the function of the LexA transcription factor from Bacillus thuringiensis. Our data indicates that the small DdrR protein from A. baumannii likely coordinates the SOS response and prophage processes by also interacting with LexA superfamily members. The discovery of DdrR's role in DNA damage response and prophage induction in A. baumannii could have significant implications for understanding and combating the threat posed by this bacterium in healthcare settings.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Biology
Cody E. FitzGerald, James P. Keener
Summary: Mycobacteria possess a complex DNA damage repair system governed by two major DNA damage responses, the LexA/RecA-dependent response and the PafBC-mediated response. The PafBC-mediated response sensitizes the overall DNA damage response and lowers the DNA damage rate threshold for activation. The mathematical characterization of the interaction between the LexA/RecA-dependent response and the PafBC-mediated response is still pending.
JOURNAL OF THEORETICAL BIOLOGY
(2021)
Article
Biochemical Research Methods
Fernanda Piorino, Mark P. Styczynski
Summary: This study investigates the impact of sonication energy inputs on the protein production capacity of cell extracts and finds that the optimal sonication energy input depends on various factors. Strategies for improving protein yields and better protocols for characterizing cell extracts are proposed.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Riyao Yang, Su Huang, Cai Huang, Nathan S. S. Fay, Yanan Wang, Saroja Putrevu, Kimberly Wright, Mohd Saif Zaman, Wenyan Cai, Betty Huang, Bo Wang, Meredith Wright, Matthew R. R. Hoag, Allison Titong, Yue Liu
Summary: Current cancer immunotherapy is mainly achieved by targeting PD-1/PD-L1 and CTLA-4 with antibodies, but their effectiveness is limited by primary and acquired resistance. Additional immune checkpoints, especially TIGIT and LAG-3, have been explored, but only a LAG-3 antibody has been approved for combination therapy for melanoma. This study reveals the potential of a new generation of multispecific checkpoint inhibitors to overcome resistance to current monospecific checkpoint antibodies or their combinations for the treatment of human cancers.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Masayuki Murata, Keiko Nakamura, Tomoyuki Kosaka, Natsuko Ota, Ayumi Osawa, Ryunosuke Muro, Kazuya Fujiyama, Taku Oshima, Hirotada Mori, Barry L. Wanner, Mamoru Yamada
Summary: The SOS response is induced upon DNA damage, and overexpression of sulA leads to cell lysis, with SoxS and LpxC playing key roles in this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Hiroshi Kagamu, Satoshi Yamasaki, Shigehisa Kitano, Ou Yamaguchi, Atsuto Mouri, Ayako Shiono, Fuyumi Nishihara, Yu Miura, Kosuke Hashimoto, Hisao Imai, Kyoichi Kaira, Kunihiko Kobayashi, Yae Kanai, Tatsuhiro Shibata, Katsuhisa Horimoto
Summary: CD4(+) T-cell immunity is essential in antitumor immune responses. A new CD4(+) T-cell metacluster associated with the efficacy of PD-1 blockade therapy has been identified, which can predict the progression-free survival and overall survival of lung cancer patients after PD-1 blockade therapy.
Article
Oncology
Lisa A. King, Elisa C. Toffoli, Myrthe Veth, Victoria Iglesias-Guimarais, Manon C. Slot, Derk Amsen, Rieneke van de Ven, Sarah Derks, Marieke F. Fransen, Jurriaan B. Tuynman, Thilo Riedl, Rob C. Roovers, Anton E. P. Adang, Jurjen M. Ruben, Paul W. H. I. Parren, Tanja D. de Gruijl, Hans J. van der Vliet
Summary: This study assessed the antitumor activity and safety of a bispecific antibody that activates Vy9V82 T cells. In vitro, in vivo, and ex vivo experiments were conducted, and safety was evaluated in nonhuman primates. The findings demonstrated the potential of the antibody to activate Vy9V82 T cells for antitumor activity and its acceptable safety profile, providing a solid basis for further testing in patients with EGFR-positive malignancies.
CANCER IMMUNOLOGY RESEARCH
(2023)