Article
Biology
Anamaria Babosan, David Skurnik, Anaelle Muggeo, Gerald B. Pier, Zeynep Baharoglu, Thomas Jove, Marie-Cecile Ploy, Sophie Griveau, Fethi Bedioui, Sebastien Vergnolle, Sophie Moussalih, Christophe de Champs, Didier Mazel, Thomas Guillard
Summary: PMQR genes promote high-level bacterial resistance to fluoroquinolone antibiotics, and we found that aminoglycosides can induce the SOS response, leading to elevated transcription of qnrD. The induction of SOS response is due to nitric oxide accumulation caused by sub-MIC of aminoglycosides.
Article
Microbiology
Anja Bosch, Magreth E. Macha, Qun Ren, Philipp Kohler, Weihong Qi, Baharak Babouee Flury
Summary: Understanding the resistance mechanisms of antibiotics in the micro-environment of the infection is crucial for evaluating their clinical applicability and preventing resistance development. This study compared the laboratory resistance evolution of Escherichia coli to delafloxacin and ciprofloxacin at different pH levels and examined the underlying resistance mechanisms. The research provides new insights into E. coli's resistance to delafloxacin and emphasizes the importance of understanding micro-environmental conditions at the infection site for the true clinical efficacy of antibiotics.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Anamaria Babosan, Margaux Gaschet, Anaelle Muggeo, Thomas Jove, David Skurnik, Marie-Cecile Ploy, Christophe de Champs, Fany Reffuveille, Thomas Guillard
Summary: Bacteria within biofilms exposed to sub-MIC concentrations of antibiotics can develop antibiotic resistance. This study shows that sub-MIC levels of aminoglycosides induce the SOS response in E. coli carrying the qnrD gene, leading to genetic rearrangements and increased biofilm formation. The presence of the qnrD-plasmid promotes biofilm production and the acquisition and spread of resistance determinants for other antibiotics.
Article
Multidisciplinary Sciences
Allison J. Lopatkin, Sarah C. Bening, Abigail L. Manson, Jonathan M. Stokes, Michael A. Kohanski, Ahmed H. Badran, Ashlee M. Earl, Nicole J. Cheney, Jason H. Yang, James J. Collins
Summary: The study discovered that Escherichia coli undergo metabolic changes when adapting to antibiotics, with some noncanonical genes implicated in antibiotic resistance. These metabolic alterations lead to decreased basal respiration, avoiding metabolic toxicity and reducing drug lethality. Additionally, some metabolism-specific mutations identified are overrepresented in the genomes of >3500 clinical E. coli pathogens, indicating clinical relevance.
Article
Multidisciplinary Sciences
Brandon Sit, Veerasak Srisuknimit, Emilio Bueno, Franz G. Zingl, Karthik Hullahalli, Felipe Cava, Matthew K. Waldor
Summary: The microbial cell wall, primarily composed of peptidoglycan, plays a crucial role in maintaining cell shape and resistance to external stressors. The biosynthesis and structure of peptidoglycan are responsive to environmental changes, however, the underlying mechanisms are not fully understood. In this study, DUF368 and DedA protein families were identified as candidate C55-P translocases, filling a critical gap in the knowledge of proteins involved in the biogenesis of microbial cell surface polymers. The activity of C55-P transporter was found to be essential for the growth and maintenance of cell shape in pathogenic bacteria, such as cholera.
Article
Multidisciplinary Sciences
Brandon Sit, Veerasak Srisuknimit, Emilio Bueno, Franz G. Zingl, Karthik Hullahalli, Felipe Cava, Matthew K. Waldor
Summary: The microbial cell wall is important for maintaining cell shape and resistance to external stressors. Peptidoglycan is the primary structural component of the cell wall and its synthesis and structure are responsive to environmental conditions. The DUF368 and DedA protein families have been identified as candidate C55-P translocases, playing a critical role in the biogenesis of microbial cell surface polymers.
Article
Microbiology
Minh-Duy Phan, Kate M. Peters, Laura Alvarez Fraga, Steven C. Wallis, Steven J. Hancock, Nguyen Thi Khanh Nhu, Brian M. Forde, Michelle J. Bauer, David L. Paterson, Scott A. Beatson, Jeffrey Lipman, Mark A. Schembri
Summary: The plasmid-associated resistance gene, AAC (6')-Ib-cr, provides a selective advantage for the dissemination of Escherichia coli ST131, a highly antibiotic resistant clone. This gene, which inactivates the fluoroquinolone antibiotic ciprofloxacin, is present in over 70% of strains from the rapidly growing subgroup of multidrug resistant ST131. The presence of this gene gives ST131 an edge even in the presence of chromosomal FQ-resistance mutations.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Vidar Sorum, Emma L. Oynes, Anna S. Moller, Klaus Harms, Orjan Samuelsen, Nicole L. Podnecky, Pal J. Johnsen
Summary: This study investigates the stability of collateral networks in ciprofloxacin-resistant Escherichia coli strains. The results show that the collateral effects caused by resistance development are not stable, complicating the general applicability and clinical implementation of collateral effects in treatment strategies.
Article
Microbiology
Lotte Jakobsen, Carina Vingsbro Lundberg, Niels Frimodt-Moller
Summary: Ciprofloxacin is highly effective in clearing urine and kidney tissue for fully susceptible E. coli, but not for low-level resistant strains. PKPD correlations show a higher correlation between AUC/MIC and effect in urine and kidneys, while %T->MIC shows a lower correlation.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Microbiology
Shivdeep Singh Hayer, Alejandro Casanova-Higes, Eliana Paladino, Ehud Elnekave, Andre Nault, Timothy Johnson, Jeff Bender, Andres Perez, Julio Alvarez
Summary: This systematic review and meta-analysis aims to describe the global prevalence of phenotypic and genotypic resistance to fluoroquinolones and colistin in Escherichia coli collected from swine. The study finds higher prevalence levels of fluoroquinolone and colistin resistance in Asian pig populations compared to Europe. There is a major knowledge gap about the situation of antimicrobial resistance in South American and African countries. The study also identifies deficiencies in how AMR data is reported and establishes the prevalence and global distribution of genetic determinants of resistance.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Infectious Diseases
Stacey S. Cherny, Daniel Nevo, Avi Baraz, Shoham Baruch, Ohad Lewin-Epstein, Gideon Y. Stein, Uri Obolski
Summary: The study analyzed clinical data and found strong associations between resistance to different antibiotics, not only within the same class but also across different bacterial species. Additionally, resistance to antibiotics was directly linked with previous antibiotic usage.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Pooja Srinivas, Rebecca E. Steiner, Ian J. Pavelich, Ricardo Guerrero-Ferreira, Puneet Juneja, Michael Ibba, Christine M. Dunham
Summary: The oxidation process in bacteria, such as Salmonella enterica serovar Typhimurium, affects the high fidelity of protein synthesis by enhancing editing accuracy and reducing misincorporation of tyrosine. This study provides insights into how oxidation-induced structural changes in Phenylalanyl-tRNA synthetase contribute to hyperaccurate editing, shedding light on the survival mechanisms of S. Typhimurium during human infection.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Elham Rastegar, Yalda Malekzadegan, Reza Khashei, Nahal Hadi
Summary: This study investigated the antibiotic resistance pattern, biofilm formation capability, distribution of quinolone resistance genes, and phylogenetic groups among UPEC isolates from Iranian hospitalized patients. The results showed high fluoroquinolone and quinolone resistance, strong biofilm formation ability, and the presence of different subtypes of quinolone resistance genes. This survey emphasizes the importance of awareness on quinolone resistance and cautious prescription by physicians.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Multidisciplinary Sciences
Peyton J. Spreacker, Nathan E. Thomas, Will F. Beeninga, Merissa Brousseau, Colin J. Porter, Kylie M. Hibbs, Katherine A. Henzler-Wildman
Summary: EmrE, a small multidrug resistance efflux pump from E. coli, can confer resistance or susceptibility depending on the small molecule substrate.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Jude Fonbah Leinyuy, Innocent Mbulli Ali, Karimo Ousenu, Christopher B. Tume
Summary: This study analyzed 200 Enterobacteriaceae isolates resistant and susceptible to ESBL, quinolones, and aminoglycosides. It found a high carriage of resistance genes, but the carriage of resistance genes may not always be correlated with phenotypic expression.
Article
Biochemistry & Molecular Biology
Linnea Garoff, Franziska Pietsch, Douglas L. Huseby, Tua Lilja, Gerrit Brandis, Diarmaid Hughes
MOLECULAR BIOLOGY AND EVOLUTION
(2020)
Article
Biochemistry & Molecular Biology
Christina Nord, Joakim Bjerketorp, Jolanta J. Levenfors, Sha Cao, Adam A. Stromstedt, Bengt Guss, Rolf Larsson, Diarmaid Hughes, Bo Oberg, Anders Broberg
ACS CHEMICAL BIOLOGY
(2020)
Article
Infectious Diseases
Lisa Praski Alzrigat, Douglas L. Huseby, Gerrit Brandis, Diarmaid Hughes
Summary: Experimental evolution did not identify any single pump-independent cost factor, but efficient fitness compensation occurred only by mechanisms that reduce MarA concentration, simultaneously reducing the drug resistance phenotype. This resistance/fitness trade-off serves as a barrier to the successful spread of MarR inactivation mutations in clinical isolates where growth fitness is essential.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Tomas Sou, Jon Hansen, Edgars Liepinsh, Maria Backlund, Onur Ercan, Solveiga Grinberga, Sha Cao, Paraskevi Giachou, Anna Petersson, Magdalena Tomczak, Malgorzata Urbas, Dorota Zabicka, Carina Vingsbo Lundberg, Diarmaid Hughes, Sven N. Hobbie, Lena E. Friberg
Summary: This study investigated the potential of using PK/PD modeling to predict the efficacious dose of aprmycin in humans and analyzed susceptibility and resistance development in different strains. The results indicate that the mechanistic PK/PD modeling approach is suitable for HED prediction and has the potential to improve predictive capacity.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Infectious Diseases
Gerrit Brandis, Susanna Granstrom, Anna T. Leber, Katrin Bartke, Linnea Garoff, Sha Cao, Douglas L. Huseby, Diarmaid Hughes
Summary: Cip(R) rpoB mutations may contribute to resistance development and induce a ppGpp-independent stringent-Like response. In addition, the resistance development in strains carrying Cip(R) rpoB alleles also depends on other factors, such as mutations in dksA.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Katrin Bartke, Linnea Garoff, Douglas L. Huseby, Gerrit Brandis, Diarmaid Hughes
Summary: Integrating E. coli DNA into the Salmonella chromosome through conjugation resulted in hybrids with reduced growth rate, but some hybrids showed no significant decrease in growth fitness. This suggests that barriers to creating high-fitness interspecies hybrids may be lower than previously thought.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Infectious Diseases
Gerrit Brandis, Jonas Gockel, Linnea Garoff, Lionel Guy, Diarmaid Hughes
Summary: The study revealed that cellular stress caused by various antibiotics can induce qepA1 gene expression. The fusion of qepA1 gene with a class I integron results in its expression driven by the Pc promoter within the integrase gene. A segment within the integron belonging to a truncated dfrB4 gene is essential for the regulation of qepA1 expression, a genetic context that is universal among all sequenced qepA alleles.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Kavita Yadav, Linnea Garoff, Douglas L. Huseby, Diarmaid Hughes
Summary: The study revealed significant phenotypic and genetic barriers to the fixation of additional RPP genes in E. coli, except for tet(Q).
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Brandon A. Berryhill, Douglas L. Huseby, Ingrid C. McCall, Diarmaid Hughes, Bruce R. Levin
Summary: The study investigates the potential of the bacteriophage PYOSa for treating Staphylococcus aureus infections, showing promising results in terms of host range and killing rate. However, issues such as failure to clear bacterial populations and the emergence of small-colony variants need to be addressed before clinical application.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Editorial Material
Biotechnology & Applied Microbiology
Marie Olliver, Laura Griestop, Diarmaid Hughes, Anna Karin Belfrage, Johan Gising, Pawel Baranczewski, Carina Vingsbo Lundberg, Anders Karlen
Summary: ENABLE is an antibacterial drug discovery and development consortium formed in 2014 as part of the Innovative Medicines Initiative (IMI) New Drugs for Bad Bugs (ND4BB) programme. With the project soon ending, a brief overview of its achievements, strengths, and weaknesses is provided.
NATURE REVIEWS DRUG DISCOVERY
(2021)
Article
Microbiology
Eva Garmendia, Gerrit Brandis, Lionel Guy, Sha Cao, Diarmaid Hughes
Summary: This study demonstrates that the rates of homologous recombination between different locations on bacterial chromosomes can vary significantly, regardless of the distance between the sites or their proximity to the replication origin. Factors such as chromosomal structure and gene orientation play a key role in determining the accessibility of each chromosomal site for recombination. Moreover, the orientation of recombination cassettes also has a significant impact on the efficiency of recombination events.
Article
Chemistry, Medicinal
Andrea Benediktsdottir, Lu Lu, Sha Cao, Edouard Zamaratski, Anders Karlen, Sherry L. Mowbray, Diarmaid Hughes, Anja Sandstrom
Summary: The incorporation of sulfonimidamide into antibacterial oligopeptides was shown to increase antibacterial activity while reducing cytotoxicity, providing a novel approach for developing new antibiotics.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sha Cao, Gerrit Brandis, Douglas L. Huseby, Diarmaid Hughes
Summary: Analysis of bacterial genomes reveals that the linear order of genes on the chromosome is often not conserved among different species. Through experimental research on Salmonella, this study provides the first evidence supporting the SNAP hypothesis, which suggests that positive selection during niche adaptation can drive rearrangements in chromosomal gene order. The findings show that the gene order on the Salmonella chromosome changed significantly and irreversibly after adaptation to a new environment.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Evolutionary Biology
Katrin Bartke, Douglas L. Huseby, Gerrit Brandis, Diarmaid Hughes
Summary: The conjugation driven by a chromosomally integrated F-plasmid can create bacteria with hybrid chromosomes. This study selected 11 interspecies hybrids between Escherichia coli and Salmonella Typhimurium and found that enlargement of chromosome size resulted in reduced growth fitness. Evolution experiments with two hybrids with enlarged chromosomes showed that the fitness cost amelioration was achieved through large deletions involving recombination between repetitive DNA sequences. In all ten independent evolution experiments, DNA from both species was removed, creating high-fitness strains with hybrid chromosomes.
GENOME BIOLOGY AND EVOLUTION
(2022)