Article
Microbiology
Philip Hinchliffe, Catherine L. Tooke, Christopher R. Bethel, Benlian Wang, Christopher Arthur, Kate J. Heesom, Stuart Shapiro, Daniela M. Schlatzer, Krisztina M. Papp-Wallace, Robert A. Bonomo, James Spencer
Summary: This study reveals the mechanism of action of two β-lactamase inhibitors, enmetazobactam and tazobactam, on CTX-M-15 β-lactamase in Escherichia coli, including the formation of protein cross-link and epimerization of amino acids.
Review
Pharmacology & Pharmacy
Xinqian Ma, Wen Xi, Deqing Yang, Lili Zhao, Wenyi Yu, Yukun He, Wentao Ni, Zhancheng Gao
Summary: Bacteria can develop increased sensitivity to certain antibiotics after acquiring resistance to another antibiotic, known as collateral sensitivity. Exploiting collateral sensitivity in treatment design could effectively suppress or reverse resistance evolution.
DRUG RESISTANCE UPDATES
(2023)
Article
Immunology
Dariusz A. Hareza, Sara E. Cosgrove, Patricia J. Simner, Anthony D. Harris, Yehudit Bergman, Rick Conzemius, Emily Jacobs, Stephan Beisken, Pranita D. Tamma
Summary: This study investigated the clinical outcomes and optimal treatment methods for patients with ESBL-E bloodstream infections that do not produce CTX-M. The findings suggest that non-CTX-M and CTX-M ESBL-E infections are equally concerning and associated with similar clinical outcomes. Meropenem may be associated with improved survival in patients with non-CTX-M ESBL-E infections, highlighting the potential benefit of comprehensive molecular diagnostics for early antibiotic optimization in ESBL-E infections.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Christopher Frohlich, Vidar Sorum, Nobuhiko Tokuriki, Pal Jarle Johnsen, Orjan Samuelsen
Summary: This study investigated the impact of cefiderocol on resistance development and the evolution of beta-lactamases from different Ambler classes. The expression of bla(KPC-2), bla(CMY-2), bla(CTX-M-15), and bla(NDM-1) significantly reduced cefiderocol susceptibility, while mutations in these enzymes further increased cefiderocol resistance. Resistance development also led to collateral changes in sensitivity to other beta-lactam drugs and functional trade-offs.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Hasan Ejaz, Sonia Younas, Khalid O. A. Abosalif, Kashaf Junaid, Badr Alzahrani, Abdullah Alsrhani, Abualgasim Elgaili Abdalla, Muhammad Ikram Ullah, Muhammad Usman Qamar, Sanaa S. M. Hamam
Summary: The colonization of ESBL-producing Enterobacteriaceae in animal gut microbiota poses a significant global threat, with a high prevalence of bla(CTX-M), bla(TEM), and bla(SHV) variants among enterobacteria. These genes, along with integrons, contribute to extensive drug resistance in human strains, highlighting the limited therapeutic options available.
Article
Multidisciplinary Sciences
Tek Narsingh Malla, Kara Zielinski, Luis Aldama, Sasa Bajt, Denisse Feliz, Brendon Hayes, Mark Hunter, Christopher Kupitz, Stella Lisova, Juraj Knoska, Jose Manuel Martin-Garcia, Valerio Mariani, Suraj Pandey, Ishwor Poudyal, Raymond G. Sierra, Alexandra Tolstikova, Oleksandr Yefanov, Chung Hong Yoon, Abbas Ourmazd, Petra Fromme, Peter Schwander, Anton Barty, Henry N. Chapman, Emina A. Stojkovic, Alexander Batyuk, Sebastien Boutet, George N. Phillips, Lois Pollack, Marius Schmidt
Summary: This study used mix-and-inject serial crystallography to trace atomic positions and elucidate essential enzymatic functions at the atomic level. The results reveal detailed information about ligand binding heterogeneity, ligand gating, cooperativity, induced fit, and conformational selection from the same set of data, providing insights into the inhibition of Mycobacterium tuberculosis enzyme by sulbactam.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Severine Rangama, Ian D. E. A. Lidbury, Jennifer M. Holden, Chiara Borsetto, Andrew R. J. Murphy, Peter M. Hawkey, Elizabeth M. H. Wellington
Summary: In this study, strains of E. coli isolated downstream of a wastewater treatment plant in a river were found to carry multiple resistance genes, including bla(CTX-M-15) encoding an ESBL. E. coli strain 48 was shown to protect susceptible E. coli strain 33 from cefotaxime through secretion of a stable ESBL for at least 24 hours. CTX-M-15 was identified as the major secreted ESBL responsible for this protective effect, suggesting a public goods service for the survival of susceptible bacteria in the presence of cefotaxime.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Amel Mhaya, Rahma Trabelsi, Sabine Aillerie, Fatima M'Zali, Dominique Begu, Slim Tounsi, Radhouane Gdoura, Corinne Arpin
Summary: Multiple ESBL-producing strains were identified in Tunisian patients, including two emerging virulent clones, ST131-C2 and ST131-C1-M27, which were found to be prevalent in both community and hospital settings.
Article
Microbiology
Cecile Emeraud, Samy Figueiredo, Remy A. Bonnin, Mouna Khecharem, Souad Ouzani, Pierre-Etienne Leblanc, Agnes B. Jousset, Nicolas Fortineau, Jacques Duranteau, Laurent Dortet
Summary: Infections caused by ESBL-KP are on the rise globally and often lead to outbreaks in ICUs. Despite enhanced hygiene measures and prevention controls during the COVID-19 pandemic, an ESBL-producing K. pneumoniae isolate still caused a nosocomial outbreak in an ICU dedicated to COVID-19 patients.
Article
Biochemistry & Molecular Biology
Satoshi Nishida, Masataka Nakagawa, Yuki Ouchi, Chiaki Sakuma, Yu Nakajima, Hisayo Shimizu, Takashi Shibata, Yasunori Kurosawa, Toshiaki Maruyama, C. J. Okumura, Nami Hatayama, Yoshinori Sato, Miwa Asahara, Shinobu Ishigaki, Taiji Furukawa, Teruo Akuta, Yasuo Ono
Summary: An LFIA based on an anti-CTX-M rabbit monoclonal antibody was developed for detecting CTX-M enzyme production in Enterobacterales, showing high sensitivity and specificity with clinical isolates. This LFIA has a low detection limit, 100% sensitivity and specificity with clinical isolates, and does not cross-react with other class A beta-lactamase producing bacteria.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Microbiology
Shihan Zeng, Jiajun Luo, Xiaoyan Li, Chao Zhuo, Aiwu Wu, Xiankai Chen, LiShao Huang
Summary: The CTX-M-55 extended-spectrum beta-lactamase (ESBL)-positive rate has been increasing in recent years, showing resistance to ceftriaxone but sensitivity to ceftazidime, cefepime, and carbapenems among isolates with bla(CTX-M-55) gene. ST1193 is a common clone strain found carrying the bla(CTX-M-55) gene. The plasmids IncI1 and IncFII, along with mobile elements like ISEcp1 and IS26, may play a key role in the dissemination of CTX-M-55 genotypes.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Lorena Lopez-Cerero, Emilio Stolz, Marina R. Pulido, Alvaro Pascual
Summary: This study reports the first occurrence of community cases of CTX-M-27-producing Shigella sonnei ST152 in Spain. These cases were resistant to quinolones and azithromycin and included both adult males and a pediatric case. The isolates were genetically similar to an Australian isolate and differed significantly from outbreak-causing strains in England.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Public, Environmental & Occupational Health
Luciano C. B. A. da Silva, Brenda Cardoso, Herrison Fontana, Fernanda Esposito, Silvia R. G. Cortopassi, Fabio P. Sellera, Nilton Lincopan
Summary: This article describes a multidrug-resistant ESBL-positive Klebsiella pneumoniae strain isolated from a dog in a veterinary intensive care unit. The strain belongs to the sequence type ST392 and displays a broad resistome and the presence of the bla(CTX-M-15) ESBL gene. Phylogenomic analysis shows the close relationship between this strain and K. pneumoniae ST392 isolated from human and animal infections.
Article
Microbiology
Mari C. Rodriguez de Evgrafov, Marius Faza, Konstantinos Asimakopoulos, Morten O. A. Sommer
Summary: The study identified universal cross-resistance and global collateral sensitivity relationships among evolved bacterial lineages, along with drug-dependent divergent and conserved evolutionary trajectories among pathogens. These findings suggest that collateral responses may be preserved across species, which could contribute to the development of treatment strategies to address antibiotic resistance.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Djahida Souna, Mourad Drissi, Iyad Almahmoud, Max Maurin
Summary: This study evaluated beta-lactam resistance in Enterobacter cloacae complex strains isolated from Algerian hospitals, with the majority identified as Enterobacter hormaechei species, particularly the subspecies E. hormaechei subsp. xiangfangensis. All strains exhibited resistance to multiple antibiotics and were found to produce ESBLs, primarily from the CTX-M-1 group, notably CTX-M-15. The identification and management of multidrug-resistant ECC strains, particularly those carrying CTX-M ESBLs, pose a significant public health challenge in Algeria.
MICROBIAL DRUG RESISTANCE
(2022)
Review
Pharmacology & Pharmacy
Shivani Singh, Anne Weiss, James Goodman, Marie Fisk, Spoorthy Kulkarni, Ing Lu, Joanna Gray, Rona Smith, Morten Sommer, Joseph Cheriyan
Summary: This article reviews the pharmacology and scientific rationale for repurposing niclosamide, an anti-helminth drug, for the treatment of COVID-19. It highlights the drug's potent antiviral activity and its pleiotropic effects in preclinical and early clinical studies. The advantages and rationale for nebulized and intranasal formulations of niclosamide are also discussed, along with an overview of ongoing clinical trials.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Karl Alex Hedin, Vanessa Emily Rees, Hongbin Zhang, Vibeke Kruse, Ruben Vazquez-Uribe, Morten Otto Alexander Sommer
Summary: This study established a robust mouse model for studying the colonisation of Saccharomyces boulardii, finding that antibiotic treatment significantly increased the colonisation levels and duration of S. boulardii in mice. The findings suggest that the antibiotic cocktail used in the study is an advantageous tool for studying S. boulardii-based probiotics and advanced microbiome therapeutics.
SCIENTIFIC REPORTS
(2022)
Article
Microbiology
Sailesh Malla, Eric van der Helm, Behrooz Darbani, Stefan Wieschalka, Jochen Foerster, Irina Borodina, Morten Otto Alexander Sommer
Summary: The lack of an active export system limits the accumulation and purification of intracellular products in industrial bio-based production processes. In this study, a novel L-lysine exporter belonging to the uncharacterized EamA superfamily was identified using metagenomic functional selection. This exporter significantly improved L-lysine tolerance and enhanced the yield and production of L-lysine in an industrial strain. This approach allows for the discovery of novel exporters and can be used to increase the productivity of bioprocesses with toxicity limitations.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Hitesh P. Gelli, Ruben Vazquez-Uribe, Morten Otto Alexander Sommer
Summary: Using cell-penetrating peptides (CPPs) is an effective strategy to improve drug absorption. Among the 9 most promising CPPs studied, 4 of them significantly increased the paracellular permeability of the intestinal barrier without compromising cellular health. Furthermore, these 4 CPPs also affected the growth of the majority of tested commensal strains.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemical Research Methods
Max van't Hof, Omkar S. Mohite, Jonathan M. Monk, Tilmann Weber, Bernhard O. Palsson, Morten O. A. Sommer
Summary: The study developed an updated metabolic model, iHM1533, of Escherichia coli Nissle 1917 (EcN) with extended representation of secondary metabolites. The model was validated and improved, and it successfully predicted targets for optimizing secondary metabolite production. This model provides a better understanding of the metabolic capabilities of EcN and aids future metabolic engineering efforts.
BMC BIOINFORMATICS
(2022)
Article
Dermatology
Jonathan I. I. Silverberg, Lars E. E. French, Richard B. B. Warren, Bruce Strober, Kim Kjoller, Morten O. A. Sommer, Philippe Andres, Jakob Felding, Anne Weiss, Deniz Tutkunkardas, Tine Skak-Nielsen, Emma Guttman
Summary: This study examined the PDE4 enzymatic activity and anti-inflammatory effects of orismilast in vitro, ex vivo, and in vivo. The results showed that orismilast selectively and potently inhibited PDE4 and demonstrated broad-spectrum anti-inflammatory activity. These findings support the clinical development of oral orismilast as a novel treatment option for chronic inflammatory skin diseases.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Article
Dermatology
Richard B. B. Warren, Bruce Strober, Jonathan I. I. Silverberg, Emma Guttman, Philippe Andres, Jakob Felding, Deniz Tutkunkardas, Kim Kjoller, Morten O. A. Sommer, Lars E. E. French
Summary: This study aimed to examine the efficacy and safety of orismilast for psoriasis treatment. The phase 2a trial found that orismilast significantly improved the condition of patients with psoriasis. The phase 1 trial tested new formulations to minimize gastrointestinal adverse reactions.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Rebecca M. Lennen, Hyun Gyu Lim, Kristian Jensen, Elsayed T. Mohammed, Patrick V. Phaneuf, Myung Hyun Noh, Sailesh Malla, Rosa A. Borner, Ksenia Chekina, Emre Ozdemir, Ida Bonde, Anna Koza, Jerome Maury, Lasse E. Pedersen, Lars Y. Schoning, Nikolaus Sonnenschein, Bernhard O. Palsson, Alex T. Nielsen, Morten O. A. Sommer, Markus J. Herrgard, Adam M. Feist
Summary: This study used an automated platform to evolve Escherichia coli to grow optimally in the presence of 11 industrial chemicals and uncovered the tolerance mechanisms. The results showed that cells are tolerized through frequent mutation of membrane transporters, cell wall-associated proteins, transcription and translation machineries, and stress signaling proteins. Osmotic stress plays a significant role in tolerance, and pre-tolerized starting isolates can greatly enhance the subsequent production of chemicals.
METABOLIC ENGINEERING
(2023)
Article
Multidisciplinary Sciences
Philip Wismer, Sarah Aparecida Soares, Kasper Alnor Einarson, Morten Otto Alexander Sommer
Summary: This study demonstrates the use of virtual reality (VR) behaviometrics for assessing compliance and physical laboratory skills. By employing machine learning and classical statistics, significant behavioral predictors were identified from a logistic regression model, accurately classifying students and biopharma company employees as experts or novices in pH meter handling tasks with 77% accuracy. Specifically, the game score and number of interactions in VR tasks requiring practical skills were found to be performance predictors. The study offers biopharma companies and academic institutions the potential to assess performance using an automatic, reliable, and simple alternative to traditional in-person assessment methods. Integrating this assessment into training tools eliminates the need for tedious post-training evaluations.
Article
Immunology
Anne Weiss, Rodinde Hendrickx, Eva Stensgaard, Mads Jellingso, Morten O. A. Sommer
Summary: Immunocompromised patients, including dialysis and kidney transplant patients, have faced an increased risk of mortality due to COVID-19 despite available countermeasures. Additional protection measures are necessary for this vulnerable population.
Article
Biotechnology & Applied Microbiology
Karl Alex Hedin, Vibeke Kruse, Ruben Vazquez-Uribe, Morten Otto Alexander Sommer
Summary: The human gastrointestinal tract plays a crucial role in human health and microorganisms engineered for therapeutic purposes have emerged as a novel approach to managing diseases. To prevent the spread of these microorganisms outside the treated individual, safe and robust biocontainment strategies are necessary.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Akanksha Rajput, Siddharth M. Chauhan, Omkar S. Mohite, Jason C. Hyun, Omid Ardalani, Leonie J. Jahn, Morten O. A. Sommer, Bernhard O. Palsson
Summary: Lactobacillaceae is an important microbial family in the food industry. Through a comprehensive pangenome analysis, we found the characteristics of core, accessory, and rare genomes, as well as a richness of biosynthetic gene clusters.
Article
Multidisciplinary Sciences
Sarunas Tumas, Trine Sundebo Meldgaard, Troels Holger Vaaben, Sara Suarez Hernandez, Annemette Tengstedt Rasmussen, Ruben Vazquez-Uribe, Sine Reker Hadrup, Morten O. A. Sommer
Summary: In this study, we optimized the delivery of biologically active IL-2 using engineered E. coli Nissle 1917. The engineered strain showed high biological activity of microbially produced IL-2 (mi-IL2) in vitro and demonstrated strong immune cell activation in a 3D tumor spheroid model. Furthermore, the engineered strain selectively colonized tumors in a murine CT26 tumor model and resulted in a modest reduction in tumor growth rate and increased levels of IL-2 in the tumor. This study provides a workflow for researchers interested in utilizing E. coli Nissle for microbial therapy against cancer.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Chrysoula Dimopoulou, Mareike Bongers, Mikael Pedersen, Martin Bahl, Morten O. A. Sommer, Martin F. Laursen, Tine R. Licht
Summary: We successfully transferred the ability to produce the health-beneficial microbial metabolite indole lactic acid (ILA) into Escherichia coli, and demonstrated its expression in vitro and in vivo. The expanding knowledge of gut microbiota's metabolic activities and their impact on health has led to growing interest in engineered probiotics. Tryptophan metabolites, especially ILA, are potential therapeutic agents with multiple beneficial effects. Our study engineered an E. coli strain that produces ILA and showed its robust production in a mouse model, offering efficient options for therapeutic interventions against gastrointestinal inflammation.
FEMS MICROBIOLOGY LETTERS
(2023)
Article
Endocrinology & Metabolism
Valeria Iannone, Ambrin Farizah Babu, Johnson Lok, Carlos Gomez-Gallego, Giuseppe D'Auria, Ruben Vazquez-Uribe, Troels Holger Vaaben, Mareike Bongers, Santtu Mikkonen, Maija Vaittinen, Ida Tikkanen, Mikko Kettunen, Anton Klavus, Ratika Sehgal, Dorota Kaminska, Jussi Pihlajamaki, Kati Hanhineva, Hani El-Nezami, Morten Otto Alexander Sommer, Marjukka Kolehmainen
Summary: This study found that Escherichia coli Nissle 1917 expressing aldafermin, combined with dietary changes, can alleviate symptoms of MASLD, including reducing body weight, liver steatosis, plasma aspartate aminotransferase, and plasma cholesterol levels. RNA sequencing and metabolomics analysis revealed the downregulation of amino acid metabolism and related receptor signaling pathways, which may be implicated in the reduction of hepatic steatosis and insulin resistance.
MOLECULAR METABOLISM
(2023)