Article
Biochemistry & Molecular Biology
Nidhi Singh, Thales Kronenberger, Andrea Eipper, Felix Weichel, Mirita Franz-Wachtel, Boris Macek, Samuel Wagner
Summary: The study found that the salt bridges in the assembly of virulence-associated T3SS are not critical, but facilitate the incorporation of the next subunit. The conserved charged residues are crucial for type III-dependent secretion and play a key role in the function of T3SS.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Julia Sanchez-Garrido, David Ruano-Gallego, Jyoti S. Choudhary, Gad Frankel
Summary: Recent studies have shown that T3SS effectors interact with each other in the host, revealing their interdependency and context-dependent essentiality, which is of great significance for understanding the pathogenesis of the pathogens.
TRENDS IN MICROBIOLOGY
(2022)
Article
Veterinary Sciences
Yaodong Zhang, Yao Wang, Hong Zhu, Zhengfei Yi, Dosseh Jean Apotre Afayibo, Chenglin Tao, Tao Li, Mingxing Tian, Jingjing Qi, Chan Ding, Shengqing Yu, Shaohui Wang
Summary: The inactivation of the DctR gene in APEC resulted in decreased biofilm formation, reduced adherence capacity, and other negative effects, which were restored through genetic complementation. Additionally, DctR positively regulates the expression of ETT2 in APEC, influencing the virulence of the pathogen.
VETERINARY RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Julie Ming Liang, Lisa Ann Burdette, Han Teng Wong, Danielle Tullman-Ercek
Summary: Protein production using bacteria is costly and inefficient. Researchers have engineered a bacterial secretion system to improve the production process by directly secreting soluble proteins into the culture media. They explored different activation methods and created strains capable of efficiently producing heterologous proteins. They also discovered a genetic relationship between T3SS regulators, hilE and hilD, further enhancing the industrial competitiveness of protein production strains.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Stephan Wimmi, Alexander Balinovic, Hannah Jeckel, Lisa Selinger, Dimitrios Lampaki, Emma Eisemann, Ina Meuskens, Dirk Linke, Knut Drescher, Ulrike Endesfelder, Andreas Diepold
Summary: Current research shows that in gastrointestinal pathogens, the external pH plays a crucial role in regulating the assembly of T3SS cytosolic components, preventing T3SS activity in the stomach and facilitating its reactivation in the intestine.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Marc-Andre Leblanc, Morgan R. Fink, Thomas T. Perkins, Marcelo C. Sousa
Summary: The study shows that effector proteins from certain bacteria can be injected into host cells through a type III secretion system. These proteins need to be partially unfolded to pass through the narrow channel. Mechanical unfolding of the proteins revealed that they exhibit low force and high mechanical compliance, facilitating efficient secretion.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Xiu-Zhen Shi, Ming-Chong Yang, Xin-Le Kang, Yan-Xue Li, Pan-Pan Hong, Xiao-Fan Zhao, Gerardo R. Vasta, Jin-Xing Wang
Summary: The activation of the IMD pathway, critical for host immunity, is mediated by the receptor SRB2 in crustaceans. Depletion of SRB2 leads to increased bacterial proliferation, shrimp mortality, and decreased expression of antimicrobial peptides. This previously unrecognized SRB2-IMD axis provides insight into the innate immune response in crustaceans and has implications for prevention and treatment strategies against shrimp diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Kevin Munoz Navarrete, Ladislav Bumba, Tatyana Prudnikova, Ivana Malcova, Tania Romero Allsop, Peter Sebo, Jana Kamanova
Summary: The study reveals that BopN is a gatekeeper of the Bordetella T3SS, responsible for regulating the secretion and translocation of the BteA effector into host cells. It is similar to gatekeepers that control access to the T3SS channel from the bacterial cytoplasm. Deletion of the bopN gene in B. bronchiseptica increased secretion of BteA, but decreased the translocation of BteA into host cell cytoplasm.
MICROBIOLOGY SPECTRUM
(2023)
Review
Microbiology
Elizabeth A. Rucks
Summary: Type III secretion systems (T3SS) are utilized by Gram-negative pathogens to deliver effector proteins into target eukaryotic cells for manipulating cell functions and enhancing pathogenesis. This review will discuss the history, biochemical characterization, and function of chlamydial T3SS, as well as the use of heterologous/surrogate models for studying it. The review will also cover the history of chlamydial effectors and recent advances in the field.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2023)
Article
Multidisciplinary Sciences
Eduardo Soto, Jorge E. Galan, Marfa Lara-Tejero
Summary: In this study, an extensive in vivo cross-linking strategy aided by structure modeling was used to investigate the sorting platform complex of type III secretion systems. The assembly process of this bacterial structure was mapped using identified cross-links as signatures for pairwise intersubunit interactions and systematic genetic deletions. Insights generated by this study could be used for the rational development of antivirulence strategies against medically important bacterial pathogens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Emily Z. Guo, Jorge E. Galan
Summary: Type III secretion systems are multiprotein molecular machines essential for the virulence of bacterial pathogens. The injectisome mediates the delivery of bacterially encoded proteins into eukaryotic target cells. The structure of the needle tip complex and its interaction with the needle filament are crucial for the translocation of effector proteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Gastroenterology & Hepatology
Ce Zhang, Min Liu, Ying Wu, Xixi Li, Chen Zhang, Douglas R. Call, Ming Liu, Zhe Zhao
Summary: In Vibrio parahaemolyticus, the expression of T3SS1 is regulated by a complex quorum sensing phosphorelay circuit involving the hybrid histidine kinase ArcB, sensor kinase LuxQ, and response regulator LuxO. The study shows that LuxQ can directly interact with ArcB under high oxygen conditions, leading to phosphorylation of LuxO and activation of T3SS1 expression. Under hypoxic conditions, ArcB autophosphorylates and phosphorylates ArcA, but ArcA does not participate in regulating T3SS1 expression.
Article
Endocrinology & Metabolism
Rong Huang, Xinxiu Bai, Xueyan Li, Xiaohui Wang, Lina Zhao
Summary: Pancreatic beta-cell dysfunction in type 2 diabetes is influenced by elevated levels of retinol-binding protein 4 (RBP4), which directly suppresses insulin synthesis through the STRA6 pathway. Lowering circulating RBP4 levels could potentially restore beta-cell function and improve hyperglycemia in diabetic mice.
Review
Immunology
Albane Jouault, Alessandra Mattos Saliba, Lhousseine Touqui
Summary: This mini-review discusses how the type III secretion system (T3SS) of Pseudomonas aeruginosa and the bacterial effectors secreted through this system can activate and manipulate the host immune response, promoting the survival and establishment of the pathogen.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Umran Ay, Martin Lenicek, Arno Classen, Steven W. M. Olde Damink, Carsten Bolm, Frank G. Schaap
Summary: The conversion of host bile salts by gut microbes generates secondary bile salt species with distinct biological and physicochemical properties. Recent research has identified a new class of microbial bile salt metabolites that can influence the composition of human gut bacteria and disease states. These microbial bile salt conjugates (MBSCs) are diverse, with almost 50 different species identified.
Article
Biochemistry & Molecular Biology
Arne Strand, San-Tai Shen, Diana R. Tomchick, Junmei Wang, Chyung-Ru Wang, Johann Deisenhofer
Summary: The presentation of antigenic peptides to T-cell receptors is crucial for the adaptive immune response. Through crystal structure determination and molecular dynamics simulations, researchers found that conformational differences within one microsecond during molecular dynamics simulations of peptide complexes with H2-M3 could be crucial to T-cell discrimination. Specifically, peptide ligands with alanine or threonine at position 6 partially exiting the binding groove could play a key role in the immune response initiation by T cells.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Yasmin Dar, Biswanath Jana, Eran Bosis, Dor Salomon
Summary: A new bacterial secretion mechanism, termed a binary effector module, has been identified where an effector and co-effector are secreted together. This mechanism is widely distributed in marine bacteria and involves direct interaction between the effector and co-effector.
Article
Multidisciplinary Sciences
Lisa N. Kinch, Qian Cong, Jananee Jaishankar, Kim Orth
Summary: Bacterial signal transduction systems are mechanisms that detect environmental changes and transmit signals to control cellular responses. This study identified a rapidly evolving superfamily of co-component systems in enteric bacteria, which are the simplest signal transduction systems consisting of input sensor and output response domains encoded in a single protein chain.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Andrea Carobbi, Simone Di Nepi, Chaya M. Fridman, Yasmin Dar, Rotem Ben-Yaakov, Isaac Barash, Dor Salomon, Guido Sessa
Summary: This study reveals that the T6SS1 gene cluster in Pab phytopathogenic bacteria is a functional antibacterial system, enabling the pathogen to outcompete rival bacteria in its natural environment. The analysis indicates that the cluster encodes antibacterial effectors and immunity proteins that eliminate competitors, and also identifies additional novel T6SS effectors.
ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Microbiology
Alexander E. Lafrance, Suneeta Chimalapati, Nalleli Garcia Rodriguez, Lisa N. Kinch, Karan Gautam Kaval, Kim Orth
Summary: Maintaining high activity of CNF1 enhances the invasion of V. parahaemolyticus, but leaves many bacteria unable to escape the endosome and complete the infection cycle, highlighting the importance of enzymatic specificity during infection.
Article
Biochemistry & Molecular Biology
Burak Gulen, Amanda Casey, Kim Orth
Summary: Small GTPases play crucial roles in cellular pathways and are targeted by pathogens during infection. AMPylation, a common post-translational modification, is utilized by pathogens to hijack GTPase signaling. Understanding the AMPylation of small GTPases by pathogens contributes to the understanding of cellular infection mechanisms.
Article
Multidisciplinary Sciences
Thomas A. Russo, Timothy C. Umland, Xiaoyi Deng, Farah El Mazouni, Sreekanth Kokkonda, Ruth Olson, Ulrike Carlino-MacDonald, Janet Beanan, Cassandra L. Alvarado, Diana R. Tomchick, Alan Hutson, Hong Chen, Bruce Posner, Pradipsinh K. Rathod, Susan A. Charman, Margaret A. Phillips
Summary: New antimicrobials are necessary for treating extensively drug-resistant Acinetobacter baumannii. The results of genetic and chemical studies suggest that the de novo pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) is essential for the survival of this bacterium. By repurposing a library of analogs developed for malaria DHODH program, researchers have identified 21 compounds with potent activity against Acinetobacter baumannii DHODH. One of these compounds, DSM186, has shown promise with minimal inhibitory concentrations against various strains of A. baumannii. These findings highlight the potential of DHODH as a target for the development of new antimicrobials for the treatment of high-risk bacterial infections.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Angela J. Zou, Lisa Kinch, Suneeta Chimalapati, Nalleli Garcia, Diana R. Tomchick, Kim Orth
Summary: This study reveals the mechanism by which pathogenic Vibrio parahaemolyticus senses and responds to bile acids. It was found that the bile acid taurodeoxycholate (TDC) activates the master regulator VtrB, leading to the induction of pathogenesis. Other bile acids, such as chenodeoxycholate (CDC), do not have this activation capability. The study also shows that CDC and TDC compete for binding to the VtrA-VtrC complex, providing insights into the selective pathogenic signaling of V.parahaemolyticus.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Karan Gautam Kaval, Suneeta Chimalapati, Sara D. Siegel, Nalleli Garcia, Jananee Jaishankar, Ankur B. Dalia, Kim Orth
Summary: It has been proposed that bacteria use a process called transertion to synthesize and insert membrane proteins. This study provides evidence that Vibrio parahaemolyticus uses transertion to assemble its type III secretion system and inject virulence factors into host cells.
NATURE COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Daniel Tchelet, Kinga Keppel, Eran Bosis, Dor Salomon
Summary: In this study, proteomics was used to identify antibacterial effectors in the secretome of Vibrio parahaemolyticus strains. The results revealed two conserved effectors and other effectors that are only present in subsets of strains, suggesting a core and accessory effector repertoire of the T6SS2 system. A conserved Rhs effector was also discovered to be required for T6SS2 activity.
Article
Microbiology
Hadar Cohen, Chaya M. Fridman, Motti Gerlic, Dor Salomon
Summary: The rise in sea surface temperature has led to the spread of Vibrio bacteria and associated human illnesses. Understanding the virulence potential and determinants of these bacteria can prepare us for emerging pathogens. In this study, we found that a toxin delivery system shared among various vibrios mediates lethality in an aquatic animal, suggesting that it may contribute to the emergence of pathogenic strains.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Tridib Mahata, Shahar Molshanski-Mor, Moran G. Goren, Miriam Kohen-Manor, Ido Yosef, Oren Avram, Dor Salomon, Udi Qimron
Summary: We have identified a novel phage-encoded inhibitor of the major cytoskeletal protein in bacterial division, FtsZ. The inhibition is shown to confer T5 bacteriophage with a growth advantage in dividing hosts. Our studies demonstrate a strategy in bacteriophages to maximize their progeny number by inhibiting escape of one of the daughter cells of an infected bacterium. They further emphasize that FtsZ is a natural target for bacterial growth inhibition.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biology
Yun-Zu Pan, Qiren Liang, Diana R. Tomchick, Jef K. De Brabander, Josep Rizo
Summary: Stimulation of autophagy through targeting Bcl-2 binding could be a potential therapy for various diseases. This study describes the NMR structure of Bcl-2 bound to a compound that inhibits Beclin 1/Bcl-2 binding more effectively than Bax/Bcl-2 binding. The structure suggests the possibility of designing compounds that disrupt Beclin 1/Bcl-2 binding and stimulate autophagy without inducing apoptosis.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Thu P. Nguyen, Min Fang, Jiwoong Kim, Baiyun Wang, Elisa Lin, Vishal Khivansara, Neha Barrows, Giomar Rivera-Cancel, Maria Goralski, Christopher L. Cervantes, Shanhai Xie, Johann M. Peterson, Juan Manuel Povedano, Monika I. Antczak, Bruce A. Posner, Colin J. B. Harvey, Brian T. Naughton, David G. Mcfadden, Joseph M. Ready, Jef K. De Brabander, Deepak Nijhawan
Summary: Orphan cytotoxins are small molecules with unknown or unclear mechanisms of action. Discovering the mechanisms of these compounds is crucial for biological research and new therapeutic drugs. By engineering cancer cell lines with inducible mismatch repair deficits, the accuracy and sensitivity of identifying resistance mutations have been improved.
CELL CHEMICAL BIOLOGY
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
Ngoc U. Nguyen, Mahmoud S. Ahmed, Yuji Nakada, Ching-Cheng Hsu, Ayman Farag, Ping Wang, Ivan Menendez-Montes, Suwannee Thet, Nicholas T. Lam, Diana R. Tomchick, Gregory Walcott, Nick V. Grishin, Jianyi J. Zhang, Hesham A. Sadek
CIRCULATION RESEARCH
(2022)
