Ulrich Kleinekathöfer, Mathias Winterhalter (Bremen),
Jean-Michel Bolla, Jean-Marie Pagès (Marseille)
Thomas Gutsmann, Michael Kolbe (CSSB)
Jean-Michel Bolla (Marseille), Mark Brönstrup (Braunschweig), Eric D. Brown (Hamilton), Dirk Bumann (Basel), Matteo Ceccarelli (Cagliari), Jürg Dreier (Basel), Philip Gribbon (Hamburg), Aigars Jirgensons (Riga), Christian Kemmer (Basel), Ulrich Kleinekathöfer (Bremen), Michael Mourez (Toulouse), Gaëtan Mislin (Strasbourg), Jean-Marie Pagès (Marseille), Klaas M Pos (Frankfurt), Isabelle Schalk (Strasbourg), Timothy Schulz-Utermoehl (Manchester), Björn Windshügel, Ulrich Zacharia (Dundee), Elena I. Zgurskaya (Oklahoma), Johannes Zuegg (Brisbane)
Speaker: Ruth Brenk, University of Bergen
Date and time: TUESDAY May 4th, 2021 at 15 pm
Zoom dial in link: zoom.us/j/99761875497
Meeting ID: 997 6187 5497
Speaker: Ulrich Zachariae (University of Dundee)
Date and time: TUESDAY April 27th at 15 pm
Dial in: https://zoom.us/j/93499334233
Speaker: Mark Brönstrup
Date: April 13, 2021, 3 p.m
Free Zoom dial in: https://zoom.us/j/95055706338
Meeting ID: 950 5570 6338
Abstract: In the so-called Trojan Horse Strategy, antibiotics are conjugated to siderophores to hijack the bacterial siderophore transport system, and thereby enhance the intracellular accumulation of drugs. We present an unexplored artificial siderophore scaffold and characterize its transport mechanism across the outer membrane, resistance mechanisms and its metabolome and transcriptome effects. The scaffold potentiates the antibiotic activity of known antibacterial drugs. In addition, first positron emission tomography (PET) data with an artificial siderophore probe coupled to a 68Ga moiety demonstrates the ability to image infections in animals. Finally, we give an update on our LC/MS-based quantification of antibiotics in subcellular compartments of several Gram-negative bacterial species.
Claudia Steinem, Göttingen
Antibiotic resistance of PorB: structure, ion flux and ampicillin binding
Dominik Ruppelt, Göttingen
Lugdunin: biophysical characterization of a potential new antibiotic
Date: March 23, 3p.m
Free dial in:
Meeting ID: 946 3804 7662
"Antibiotic resistance of PorB: structure, ion flux and ampicillin binding"
Speaker: Claudia Steinem, Göttingen
"Lugdunin: biophysical characterization of a potential new antibiotic"
Speaker: Dominik Ruppelt, Göttingen
Date: March 23rd, 3 p.m
Free Zoom dial in: https://zoom.us/j/94638047662
Meeting ID: 946 3804 7662
Speaker: Olga Genilloud, Fundacion Medina
Date: Tuesday, March 2nd, 2021, 15.30 p.m
Free Zoom dial in: https://zoom.us/j/92238793287
Meeting ID: 922 3879 3287
Speaker: Klaas Martin Pos
Tuesday, Feb 9, 3.30 p.m
Zoom dial in: https://zoom.us/j/99954059823
Gram-negative bacteria maintain an intrinsic resistance mechanism against entry of noxious compounds by utilizing highly efficient tripartite efflux pumps. The archetype E. coli AcrAB-TolC tripartite drug efflux pump contains the inner membrane H+/drug antiporter AcrB comprising three functionally interdependent protomers, cycling consecutively through the loose (L), tight (T) and open (O) state during cooperative catalysis. The L protomer access pocket (AP) and T protomer deep binding pocket (DBP) inside the periplasmic porter domain (PD) have the propensity to bind many different antimicrobials. On the other hand, the transmembrane domain of AcrB is until now postulated only to be involved in the energy transduction by binding and releasing protons, giving directionality to the postulated „LTO“ conformational cycling.
Klaas Martin Pos will present structural and functional data suggesting that the transmembrane domain is involved in allosteric drug binding.
Date: Tuesday, January, 26th 2021 at 2 pm
Dial in via Zoom: https://zoom.us/j/91220440925
"Gram-negative bacteria have evolved a complex double-membrane cell envelope, with the two membranes having orthogonal sieving properties. A number of potential antibacterial compounds with intracellular targets fail to inhibit gram-negatives because they are prevented from reaching their targets within the cell by this double-membrane barrier. Quantifying and understanding antibiotic transport across these membranes is hence crucial for the rational design of new antibiotics.
We have developed multiple, complementary approaches to study this problem. One set of assays quantifies antibiotic transport across well-defined biomimetic vesicle membranes, where transport across lipid barriers and porins can be precisely measured in a range of conditions. These methods synergise with whole-cell approaches and mathematical modelling that we have developed, where antibiotic accumulation can be studied in individual bacteria trapped in a microfluidic device in real-time. These complementary biophysical approaches offer new tools to investigate this complex membrane transport phenomenon, which will in turn benefit academic and industry scientists developing new antibacterial compounds."
Dial in via Zoom: https://zoom.us/j/98886770244
Abstract: Antibiotics that inhibit multiple bacterial targets offer a promising therapeutic strategy against resistance evolution, but developing such antibiotics is challenging. Here we demonstrate that a rational design of balanced multitargeting antibiotics is feasible by using a medicinal chemistry workflow. The resultant lead compounds belonging to a novel chemical class, almost equipotently inhibit bacterial DNA gyrase and topoisomerase IV complexes and interact with multiple evolutionary conserved amino acids in the ATP-binding pockets of their target proteins. Compounds are excellently potent against a broad range of gram-positive bacteria.