Article
Infectious Diseases
Jenifer Cuesta Bernal, Jasmin El-Delik, Stephan Goettig, Klaas M. Pos
Summary: The study found that the Gram-negative bacterium AcrD efflux pump confers resistance to various antibiotics, including some previously unreported substrates. Substitution analyses of AcrD revealed key amino acid residues involved in drug binding and transport.
Article
Infectious Diseases
Esther Boyer, Jean Dessolin, Margaux Lustig, Marion Decossas, Gilles Phan, Quentin Cece, Gregory Durand, Veronique Dubois, Joris Sansen, Jean-Christophe Taveau, Isabelle Broutin, Laetitia Daury, Olivier Lambert
Summary: This study reveals the Q93R MexA mutation and the OprM C-terminal peptide as molecular determinants modulating the assembly process efficacy with cognate and non-cognate OMFs, even though they are outside the interfacial contact. It provides insights into how OMF selectivity operates during the formation of the tripartite complex.
Article
Microbiology
Justyna W. Adamiak, Varsha Jhawar, Vincent Bonifay, Courtney E. Chandler, Inga Leus, Robert K. Ernst, Herbert P. Schweizer, Helen Zgurskaya
Summary: The study analyzed the adaptive response of P. aeruginosa lacking RND-mediated efflux activities, revealing significant changes in several key pathways to protect the cell envelope. The findings demonstrate that the cells accumulate PQS signals triggering iron starvation and activation of siderophore biosynthesis, leading to lipid A modification and membrane protection through a transcriptionally regulated RND pump.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Nawarat Somprasong, Jinhee Yi, Carina M. Hall, Jessica R. Webb, Jason W. Sahl, David M. Wagner, Paul Keim, Bart J. Currie, Herbert P. Schweizer
Summary: Burkholderia cepacia complex (Bcc) and Burkholderia pseudomallei complex (Bpc) species are typically multidrug resistant, with dominant resistance mechanisms mediated by efflux pumps of the RND family. Comparative bioinformatic and functional studies suggest that RND pump-based resistance mechanisms are conserved in Burkholderia, providing a basis for adopting a uniform RND efflux pump nomenclature.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Maoge Zang, Hugo MacDermott-Opeskin, Felise G. Adams, Varsha Naidu, Jack K. Waters, Ashley B. Carey, Alex Ashenden, Kimberley T. McLean, Erin B. Brazel, Jhih-Hang Jiang, Alessandra Panizza, Claudia Trappetti, James C. Paton, Anton Y. Peleg, Ingo Koper, Ian T. Paulsen, Karl A. Hassan, Megan L. O'Mara, Bart A. Eijkelkamp
Summary: This study explores the impact of host-derived polyunsaturated fatty acids (PUFAs) on Acinetobacter baumannii's susceptibility to antibiotics, specifically by affecting AdeB-mediated antibiotic resistance. The findings suggest that A. baumannii's unconditional desire for fatty acids may present a possible weakness in its multidrug resistance capacity.
Article
Microbiology
Pauline Ann Siasat, Jessica M. A. Blair
Summary: Multidrug efflux pumps are molecular machines in the bacterial cell membrane that pump molecules out of the cell, contributing to antibiotic resistance. Understanding the characteristics of different families of efflux pumps is crucial for developing new therapies.
Review
Pharmacology & Pharmacy
Teresa Gil-Gil, Pablo Laborda, Luz Edith Ochoa-Sanchez, Jose Luis Martinez, Sara Hernando-Amado
Summary: This article introduces the resistance-nodulation-division (RND) family, which is the most important group of multidrug efflux pumps in Gram-negative bacteria, and discusses their inhibition strategies, examples of inhibitors, and the use of efflux pumps as targets for antivirulence compounds. The study of efflux pumps' overexpression can guide strategies to tackle resistance acquisition.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Pharmacology & Pharmacy
Andrea Catte, Venkata K. Ramaswamy, Attilio Vittorio Vargiu, Giuliano Malloci, Andrea Bosin, Paolo Ruggerone
Summary: This study investigates the structural dynamics and molecular determinants of resistance-nodulation-cell division (RND) transporters in Gram-negative bacteria, focusing on MexB, MexF, and MexY. By performing molecular dynamics simulations and mapping binding propensities, the researchers reveal the common recognition topology of Mex transporters, which can be used to optimize antimicrobial compound transport and inhibition.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Microbiology
Seiji Yamasaki, Naoki Koga, Martijn Zwama, Keisuke Sakurai, Ryosuke Nakashima, Akihito Yamaguchi, Kunihiko Nishino
Summary: This study found that different Trp mutations at different locations in the structure of MexB can affect the inhibitory effect of EPIs, without affecting the function of the efflux pumps.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Cristiana Mateus, Ana Rita Nunes, Monica Oleastro, Fernanda Domingues, Susana Ferreira
Summary: The study found that mutant strains from three efflux pumps were more susceptible to various classes of antimicrobials and showed increased accumulation of ethidium bromide, suggesting a potential role of efflux pumps in antimicrobial extrusion. Mutant strains did not have growth defects but showed a decrease in relative fitness. Mutant strains were more susceptible to oxidative stress, especially the AreGHI efflux pump mutation, and had impaired biofilm formation ability, increased susceptibility to human serum, and reduced adherence to intestinal epithelial cells.
Review
Infectious Diseases
Viola Camilla Scoffone, Gabriele Trespidi, Giulia Barbieri, Samuele Irudal, Elena Perrin, Silvia Buroni
Summary: This review summarizes the principal RND efflux pump families described in CF pathogens, with a focus on the main Gram-negative bacterial species, where RND pumps have been associated with MDR phenotypes.
Review
Infectious Diseases
Martijn Zwama, Kunihiko Nishino
Summary: The rise in multidrug resistance poses a major threat to human health globally due to the over-expression of multidrug efflux pumps and amino acid substitutions within the pumps themselves causing increased drug efflux efficiency. Studies on clinically, environmentally and laboratory-evolved Gram-negative bacterial strains have shown mutations in the RND-type pumps leading to decreased drug sensitivity. Understanding the evolution and variations in efflux pumps is crucial for the development of novel antibiotics and efflux pump inhibitors.
Review
Infectious Diseases
Anne Davin-Regli, Jean-Marie Pages, Aurelie Ferrand
Summary: Antibiotic efflux is a well-documented mechanism in bacteria for multidrug resistance, facilitating adaptation to high concentrations of antibiotics. Efflux pumps are frequently found in Gram-negative bacteria and expel a wide range of antibiotics, but there is currently no real-time quantification method. The development of a routine diagnostic tool is urgently needed for the rational use of antibiotics.
Article
Biochemistry & Molecular Biology
Pierpaolo Cacciotto, Andrea Basciu, Francesco Oliva, Giuliano Malloci, Martin Zacharias, Paolo Ruggerone, Attilio V. Vargiua
Summary: Efflux pumps of the RND superfamily play a role in antibiotic resistance by expelling antibiotics from Gram-negative pathogens. This study investigated the stability of MexA, a membrane fusion protein, and the impact of a mutation on its function. The results show that MexA dimers are stable, but the mutation disrupts the protein's conformational equilibrium, making dimer or higher order assemblies unlikely.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Infectious Diseases
Arnaud Magallon, Mathilde Roussel, Catherine Neuwirth, Jennifer Tetu, Anne-Charlotte Cheiakh, Baptiste Boulet, Veronique Varin, Victor Urbain, Julien Bador, Lucie Amoureux
Summary: In Achromobacter, fluoroquinolone resistance is primarily due to overproduction of the RND efflux system AxyEF-OprN, rather than target alteration. This was demonstrated in one in vitro mutant.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Biology
R. Christopher D. Furniss, Nikol Kaderabkova, Declan Barker, Patricia Bernal, Evgenia Maslova, Amanda A. A. Antwi, Helen E. McNeil, Hannah L. Pugh, Laurent Dortet, Jessica M. A. Blair, Gerald Larrouy-Maumus, Ronan R. McCarthy, Diego Gonzalez, Despoina A. Mavridou
Summary: Antimicrobial resistance in Gram-negative bacteria poses a major threat to global health, and the development of new antibacterial strategies is urgently needed. This study demonstrates that disrupting cell envelope protein homeostasis can simultaneously compromise multiple classes of resistance determinants, laying the foundation for the development of broad-acting antibiotic adjuvants.
Article
Multidisciplinary Sciences
Pablo Catalan, Emily Wood, Jessica M. A. Blair, Ivana Gudelj, Jonathan R. Iredell, Robert E. Beardmore
Summary: This study explores the trends in antibiotic resistance using the global database ATLAS and compares the results with other surveillance data.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Ilyas Alav, Vassiliy N. Bavro, Jessica M. A. Blair
Summary: Tripartite resistance-nodulation-division (RND) efflux pumps, including the PAP, play a crucial role in antibiotic resistance. Investigation of the binding residues between PAP and RND transporter contributes to understanding their assembly and transport mechanism, offering potential strategies to combat antibiotic resistance.
SCIENTIFIC REPORTS
(2022)
Article
Infectious Diseases
Jessica M. A. Blair, Pauline Siasat, Helen E. McNeil, Abigail Colclough, Vito Ricci, Amelia J. Lawler, Hind Abdalaal, Michelle M. C. Buckner, Alison Baylay, Stephen J. Busby, Laura J. Piddock
Summary: In this study, it was found that EnvR is a potent repressor of acrAB transcription in Salmonella, and can override binding by RamA, thus preventing multidrug resistance to clinically useful drugs. Finding novel tools to increase EnvR expression may form the basis of a new way to prevent or treat multidrug-resistant infections.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Review
Immunology
Camus Nimmo, James Millard, Valwynne Faulkner, Johana Monteserin, Hannah Pugh, Eachan Oliver Johnson
Summary: Mycobacterium tuberculosis has developed drug resistance to all drugs used against it, and this resistance can spread rapidly amongst bacterial populations. Resistance-conferring mutations often come with a fitness cost, but compensatory mutations can restore fitness. The acquisition of drug resistance occurs through low-frequency within-host variation and ongoing purifying selection. It is important to understand the implications of resistance evolution as countries adopt genomic methods for diagnosis and drug resistance testing.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Farhana Alam, Jessica M. A. Blair, Rebecca A. Hall
Summary: This study demonstrated that the presence of Candida albicans in Pseudomonas aeruginosa biofilms enhances the tolerance to meropenem, possibly through the induction of additional efflux pumps. Transcription profiling revealed differential gene expression involved in interkingdom interactions and biofilm formation as the main molecular mechanisms for this phenomenon.
Review
Microbiology
Elizabeth M. Darby, Eleftheria Trampari, Pauline Siasat, Maria Solsona Gaya, Ilyas Alav, Mark A. Webber, Jessica M. A. Blair
Summary: Antibiotic resistance is a global health emergency, and understanding the molecular mechanisms that bacteria use to resist antimicrobials is critical. Recent advances in research can aid in developing new antimicrobial therapies.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Microbiology
Hannah L. Pugh, Christopher Connor, Pauline Siasat, Alan McNally, Jessica M. A. Blair
Summary: Escherichia coli is a facultative anaerobe commonly found in various environments. This study shows that the presence of resistance-nodulation-division (RND) efflux pumps in laboratory bacterial strains may not reflect the situation in virulent strains of bacterial pathogens, using E. coli ST11 as an example. The absence of acrF and the conserved insertion in its gene were observed in 97.59% of ST11 genome assemblies, and the non-functionality of AcrF in ST11 was confirmed in laboratory experiments.
Article
Veterinary Sciences
Shanshan Shen, Yawei Sun, Fei Ren, Jessica M. A. Blair, Pauline Siasat, Shuaiqi Fan, Jianhe Hu, Junping He
Summary: This study demonstrated that OaBac5mini is a stable and potent PrAMP that kills E. coli by inhibiting intracellular targets and damaging the cell membrane.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Article
Microbiology
Pauline Ann Siasat, Jessica M. A. Blair
Summary: Multidrug efflux pumps are molecular machines in the bacterial cell membrane that pump molecules out of the cell, contributing to antibiotic resistance. Understanding the characteristics of different families of efflux pumps is crucial for developing new therapies.
Article
Chemistry, Multidisciplinary
Asier R. R. Muguruza, Alessandro di Maio, Nikolas J. J. Hodges, Jessica M. A. Blair, Zoe Pikramenou
Summary: In this study, a novel hybrid silica nanoparticle system was designed, which carried membrane targeting groups and encapsulated antibiotics along with a ruthenium luminescent tracking agent for optical detection of nanoparticle delivery in bacterial cells. The hybrid system successfully delivered vancomycin and exhibited efficacy against various Gram-negative bacterial species. The penetration of nanoparticles in bacterial cells was confirmed via the luminescence of the ruthenium signal. These findings demonstrate that nanoparticles modified with aminopolycarboxylate chelating groups can serve as an effective delivery system for inhibiting bacterial growth in species where molecular antibiotics are ineffective. This design provides a new platform for delivering antibiotics that cannot penetrate the bacterial membrane alone.
NANOSCALE ADVANCES
(2023)
