Review
Infectious Diseases
Marin Kollef, Herve Dupont, David E. Greenberg, Pierluigi Viale, Roger Echols, Yoshinori Yamano, David P. Nicolau
Summary: Carbapenem-resistant Acinetobacter baumannii (CRAB) has been classified as a critical pathogen requiring urgent new antibiotic treatment options. Cefiderocol, the first approved siderophore cephalosporin, shows stable activity against carbapenem-resistant pathogens and has demonstrated clinical efficacy in treating CRAB infections. Combination therapy with other active antibiotics and monitoring for resistance development are recommended.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Microbiology
Patricia Koenig, Alexander Wilhelm, Christoph Schaudinn, Anja Poehlein, Rolf Daniel, Marek Widera, Beate Averhoff, Volker Mueller
Summary: In this study, a new survival strategy of Acinetobacter baumannii, called viable but non-culturable (VBNC) state, was identified. This state allows the bacteria to survive under unfavorable conditions and evade classical detection methods, thereby impacting the detection and recurring infections of A. baumannii.
Article
Genetics & Heredity
Irene Artuso, Harsh Poddar, Benjamin A. Evans, Paolo Visca
Summary: Acinetobacter baumannii uses multiple iron acquisition strategies to obtain iron in low iron environments, which may contribute to its proliferation in human and animal infections. Among more than 1000 genotypically diverse A. baumannii isolates, the iron uptake gene clusters feo, hemT, bfn, and bas/bau are highly prevalent, while the hemO and fbs gene clusters are rare.
MICROBIAL GENOMICS
(2023)
Article
Chemistry, Medicinal
Keith D. Green, Nishad Thamban Chandrika, Loan Y. Vu, Allan H. Pang, Oleg V. Tsodikov, Sylvie Garneau-Tsodikova
Summary: The emergence of multidrug-resistant bacteria and the poor efficacy of available antibiotics have led to the urgent need for novel antibiotics. In this study, we synthesized a series of 46 aromatic hydrazides as potential treatments for A. baumannii infections. 34 compounds showed low-to sub-mu M inhibitory effects on A. baumannii growth and demonstrated high potency against multidrug-resistant clinical isolates, while being non-toxic to mammalian cells. These compounds have the potential to be developed into a selective anti-A. baumannii antibiotic.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jinping Yang, Timothy A. Wencewicz
Summary: The in vitro reconstitution of Fimsbactin A biosynthesis using purified enzymes has provided valuable insights into the mechanism of synthesis, including the sequential actions of enzymes and substrate selectivity. This study sheds light on the development of inhibitors, vaccines, and therapeutic strategies.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Tabbetha J. Bohac, Luting Fang, Victoria S. Banas, Daryl E. Giblin, Timothy A. Wencewicz
Summary: The synthetic siderophores can act as versatile structural and biomimetic analogues of native siderophores in targeting the pathogenic Gram-negative human pathogen Acinetobacter baumannii, with potential therapeutic applications as chemical probes or drugs. The metal-free and ferric iron complexes of the synthetic siderophores promote growth of A. baumannii, while the Ga(III)-complexes inhibit its growth effectively with low MIC values. Additionally, the synthetic siderophores compete with native siderophores for uptake in A. baumannii and maintain comparable binding affinities for ferric iron and siderophore-binding protein BauB, offering new insights for the development of siderophore-based therapeutics targeting pathogenic strains of A. baumannii.
ACS INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
Yoshinori Yamano, Naoki Ishibashi, Miho Kuroiwa, Miki Takemura, Wang-Huei Sheng, Po-Ren Hsueh
Summary: This study conducted in Taiwan demonstrated that the addition of avibactam could significantly decrease the minimum inhibitory concentration of CFDC-non-susceptible CRAB isolates, indicating the involvement of beta-lactamases in resistance.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2022)
Article
Microbiology
Irina Buchovec, Laurita Klimkaite, Edita Suziedeliene, Saulius Bagdonas
Summary: Antimicrobial photodynamic therapy (aPDT) based on riboflavin and chlorophyllin can effectively inactivate Acinetobacter baumannii and Stenotrophomonas maltophilia, especially for biofilm bacteria.
Article
Microbiology
Hing Jian Mea, Phelim Voon Chen Yong, Eng Hwa Wong
Summary: Acinetobacter baumannii, a Gram-negative opportunistic pathogen, has gained notoriety in recent years for causing nosocomial infections in critically ill patients. Its global spread, multidrug resistance, and numerous virulence factors pose a serious threat to public health worldwide. Despite efforts to understand its successes, researchers are still confounded by its highly adaptive nature.
MICROBIOLOGICAL RESEARCH
(2021)
Article
Microbiology
Stefano Stracquadanio, Carmelo Bonomo, Andrea Marino, Dafne Bongiorno, Grete Francesca Privitera, Dalida Angela Bivona, Alessia Mirabile, Paolo Giuseppe Bonacci, Stefania Stefani
Summary: This study investigates the interactions between a novel cephalosporin called cefiderocol (FDC) and different strains of Acinetobacter baumannii with varying susceptibilities to the drug. The results show diverse susceptibility profiles and the possibility of non-susceptible phenotypes at high drug concentrations. Combination therapy could potentially eliminate drug-adapted subpopulations and restore full activity of FDC.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Patricia Koenig, Beate Averhoff, Volker Mueller
Summary: Acinetobacter baumannii is a global threat to healthcare institutions due to its multiple antibiotic resistances and ability to persist in low water activity environments. Deletion of K+ transporter genes in A. baumannii results in growth defects and metabolic dysfunction, affecting its pathogenicity in the host. The mutants also show reduced resistance to reactive oxygen species and impaired virulence, providing insights into the importance of K+ uptake in pathogenicity.
INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY
(2021)
Article
Infectious Diseases
Davide Carcione, Claudia Siracusa, Adela Sulejmani, Roberta Migliavacca, Alessandra Mercato, Aurora Piazza, Luigi Principe, Nicola Clementi, Nicasio Mancini, Valerio Leoni, Jari Intra
Summary: The study demonstrates that cefiderocol exhibits in vitro antimicrobial activity against both carbapenem-susceptible and non-susceptible Acinetobacter baumannii strains, although resistance was observed in some OXA-23-like producers. Further clinical studies are needed to further evaluate the efficacy of cefiderocol against multidrug-resistant A. baumannii strains.
Article
Biochemistry & Molecular Biology
Xue-Min Jia, Cheng Cheng, Ting Liu, Yong-Long Zhao, Bing Guo, Lei Tang, Yuan-Yong Yang
Summary: This study synthesized 39 N-acyl-2-aminopyrimidine derivatives and tested their inhibition efficacy on A. baumannii biofilm. Some of the analogues showed potential clinical significance and were demonstrated to be quorum sensing inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Kelly Conde-Perez, Juan C. Vazquez-Ucha, Laura Alvarez-Fraga, Lucia Ageitos, Soraya Rumbo-Feal, Marta Martinez-Guitian, Noelia Trigo-Tasende, Jaime Rodriguez, German Bou, Carlos Jimenez, Alejandro Beceiro, Margarita Poza
Summary: This study revealed the critical role of acinetobactin and its receptor bauA in the pathogenicity of A. baumannii, and identified key genes in the acinetobactin cluster that are essential for bacterial virulence. The findings suggest potential targets for developing new antivirulence agents against this microorganism.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Somshukla Chaudhuri, Iraj Rasooli, Ramin Hatefi Oskouei, Mahdi Pishgahi, Abolfazl Jahangir, Vahid Farshchi Andisi, Anthony B. Schryvers
Summary: This study aimed to develop a novel vaccine antigen against Acinetobacter baumannii, a bacterium that is of increasing concern due to its antibiotic resistance and lack of effective therapeutics. The researchers utilized a hybrid antigen approach to display exposed loops of the outer membrane receptor BauA, which plays a crucial role in nutrient acquisition, in order to induce an immune response. The results showed that immunization with hybrid antigens displaying specific loops provided protection, with the hybrid antigen displaying loop 7 being particularly effective in completely preventing infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lisa S. Mydy, Daniel C. Bailey, Ketan D. Patel, Matthew R. Rice, Andrew M. Gulick
Article
Biochemistry & Molecular Biology
Ce Shi, Bradley R. Miller, Evan M. Alexander, Andrew M. Gulick, Courtney C. Aldrich
ACS CHEMICAL BIOLOGY
(2020)
Article
Chemistry, Medicinal
Evan M. Alexander, Dale F. Kreitler, Valeria Guidolin, Alexander K. Hurben, Eric Drake, Peter W. Villalta, Silvia Balbo, Andrew M. Gulick, Courtney C. Aldrich
ACS INFECTIOUS DISEASES
(2020)
Article
Immunology
Shunsuke Sakai, Keith D. Kauffman, Sangmi Oh, Christine E. Nelson, Clifton E. Barry, Daniel L. Barber
Summary: The study found that MAIT cells mount minimal responses following Mtb infection, but MAIT cell expansion during chronic infection can reduce bacterial loads. The 5-OP-RU vaccination failed to protect against Mtb challenge, but MAIT cells play a role in delaying T cell priming.
MUCOSAL IMMUNOLOGY
(2021)
Review
Parasitology
Carolina M. Koeller, Terry K. Smith, Andrew M. Gulick, James D. Bangs
Summary: p67 is a type I transmembrane glycoprotein located in the terminal lysosome of African trypanosomes. Knockdown of p67 is lethal, resulting in an enlarged lysosome. Orthologues of p67 have been identified in Dictyostelium and mammals, and are believed to possess phospholipase B-like activity.
Article
Chemistry, Physical
Anil R. Mhashal, Adrian Romero-Rivera, Lisa S. Mydy, Judith R. Cristobal, Andrew M. Gulick, John P. Richard, Shina C. L. Kamerlin
Review
Biochemical Research Methods
Girish Swayambhu, Michael Bruno, Andrew M. Gulick, Blaine A. Pfeifer
Summary: Siderophore natural products are characterized by their ability to tightly chelate metals, with origins often found in pathogenic microbes. Despite the traditional association with pathogenicity, the evolutionarily-optimized binding abilities of siderophores suggest potential for redirection towards alternative beneficial applications.
CURRENT OPINION IN BIOTECHNOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Ketan D. Patel, Andrew M. Gulick
Summary: The study of natural products presents opportunities for discovering novel biologically active molecules and biosynthetic pathways. For example, research on cyclic depsipeptides biosynthesized by marine fungi can lead to insights into their synthesis and antiviral properties, such as inhibiting Zika virus replication.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Bree B. Aldridge, David Barros-Aguirre, Clifton E. Barry, Robert H. Bates, Steven J. Berthel, Helena I. Boshoff, Kelly Chibale, Xin-Jie Chu, Christopher B. Cooper, Veronique Dartois, Ken Duncan, Nader Fotouhi, Fabian Gusovsky, Philip A. Hipskind, Dale J. Kempf, Joel Lelievre, Anne J. Lenaerts, Case W. McNamara, Valerie Mizrahi, Carl Nathan, David B. Olsen, Tanya Parish, H. Michael Petrassi, Alexander Pym, Kyu Y. Rhee, Gregory T. Robertson, Jeremy Michael Rock, Eric J. Rubin, Betsy Russell, David G. Russell, James C. Sacchettini, Dirk Schnappinger, Michael Schrimpf, Anna M. Upton, Peter Warner, Paul Graham Wyatt, Ying Yuan
Summary: The Tuberculosis Drug Accelerator has successfully facilitated collaboration in tuberculosis drug discovery, breaking down barriers among competing labs and institutions. The achievements, advantages, and limitations of the consortium suggest that similar models could be applied to research on other diseases.
Editorial Material
Immunology
Clifton E. Barry, Katrin D. Mayer-Barber
Summary: Despite the majority of humans infected with Mycobacterium tuberculosis not showing clinical symptoms, predicting those who will remains challenging. Recent studies have revealed patterns and pathways that determine who is at highest risk for progression.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Editorial Material
Critical Care Medicine
Christoph Lange, Clifton E. Barry, C. Robert Horsburgh
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Biology
Kira S. Makarova, Brittney Blackburne, Yuri Wolf, Anastasia Nikolskaya, Svetlana Karamycheva, Marlene Espinoza, Clifton E. Barry, Carole A. Bewley, Eugene Koonin
Summary: This study comprehensively analyzed BGCs encoding graspetides and reported several novel graspetide groups and associated proteins involved in their biosynthesis and expression. The results revealed previously unsuspected diversity in graspetide sequences and expanded the known diversity of RiPPs. The findings of this study are important for advancing approaches to identify RiPPs.
Article
Biochemistry & Molecular Biology
Jinping Yang, Victoria S. Banas, Ketan D. Patel, Gerry S. M. Rivera, Lisa S. Mydy, Andrew M. Gulick, Timothy A. Wencewicz
Summary: Siderophores are metabolites used by microbes to sequester environmental iron. Streptomyces strains produce desferrioxamine (DFO) siderophores, which consist of repeating units of hydroxamate-based desferrioxamine and succinate. In this study, we characterized four DesD orthologs from Streptomyces strains that produce unique DFO siderophores. We synthesized a structural mimic of N-1-hydroxy-N-1-succinyl-cadaverine and obtained crystal structures of DesD in different forms. Our findings suggest that acyl-AMS derivatives can be useful tools to study the mechanism and structure of this family of enzymes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Neurosciences
Ute Haeussler, Joao Neres, Catherine Vandenplas, Caroline Eykens, Irena Kadiu, Carolin Schramm, Renaud Fleurance, Phil Stanley, Patrice Godard, Laurane de Mot, Jonathan van Eyll, Klaus-Peter Knobeloch, Carola A. Haas, Stefanie Dedeurwaerdere
Summary: Structural epilepsies display complex immune activation signatures, but the specific neuroinflammatory pathways driving the pathology are unclear. Transcriptome studies in patients with mesial temporal lobe epilepsy (mTLE) identified dysregulation of transforming growth factor beta, interferon alpha/beta, and nuclear factor erythroid 2-related factor 2 pathways. However, in a mouse model, lack of Usp15 did not significantly affect severity of status epilepticus or the expression of inflammatory pathways.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ketan D. Patel, Monica R. MacDonald, Syed Fardin Ahmed, Jitendra Singh, Andrew M. Gulick
Summary: Nonribosomal peptide synthetases (NRPSs) are enzymes that catalyze the biosynthesis of important peptide natural products. The NRPS architecture involves an assembly line strategy that tethers amino acid building blocks and growing peptides. While conserved conformational states have been identified within a single module, interactions between modules are more dynamic. This article describes the structures of NRPS protein domains and modules and discusses their implications for future natural product discovery.
NATURAL PRODUCT REPORTS
(2023)