Article
Microbiology
Zhenzhen Ma, Congjuan Xu, Xinxin Zhang, Dan Wang, Xiaolei Pan, Huimin Liu, Guangbo Zhu, Fang Bai, Zhihui Cheng, Weihui Wu, Yongxin Jin
Summary: Therapy for Pseudomonas aeruginosa infections is challenging due to its high antibiotic resistance. The study reveals that hyperexpression of an efflux pump MexAB-OprM caused by a R70Q substitution in MexR contributes to increased resistance to aztreonam in clinical isolates. This finding sheds light on the mechanism of antibiotic resistance development in P. aeruginosa.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Ecology
Thomas James O'Brien, Wendy Figueroa, Martin Welch
Summary: The presence of diverse polymicrobial communities in the airways of individuals with cystic fibrosis can hinder the effectiveness of antibiotic treatment. A study showed that growth in a polymicrobial environment protects the target microorganism from the effects of specific antimicrobial agents. This decreased efficacy is found to have both physiological and genetic components.
Article
Immunology
Anke Neidig, Nikola Strempel, Nadine Bianca Waeber, Waleska Stephanie da Cruz Nizer, Joerg Overhage
Summary: The multidrug efflux systems of the resistance-nodulation-cell division (RND) family play a critical role in the resistance of Pseudomonas aeruginosa to various antibiotics. This study investigated the involvement of clinically relevant efflux pumps, such as MexAB(-)OprM, MexCD(-)OprJ, and MexXY(-)OprM, in the resistance against different cationic antimicrobial peptides (AMPs). The findings suggest that MexXY-OprM contributes to the resistance of P. aeruginosa to certain AMPs, highlighting the importance of considering this efflux pump in the development of new and highly active antimicrobial peptides to combat multidrug-resistant infections.
MICROBIOLOGY AND IMMUNOLOGY
(2023)
Review
Infectious Diseases
Asiyeh Avakh, Gary D. Grant, Matthew J. Cheesman, Tejaswini Kalkundri, Susan Hall
Summary: Pseudomonas aeruginosa (P. aeruginosa) is a problematic bacterium due to its multidrug resistance (MDR) phenotype. It exhibits intrinsic and acquired resistance to many antibiotics, and efflux pumps, particularly the Mex pumps, play a crucial role in driving MDR. Developing efflux pump inhibitors (EPIs) holds great potential for overcoming MDR and restoring the efficacy of antipseudomonal drugs.
Article
Immunology
Ying Liu, Rui Zhu, Xinwei Liu, Dengzhou Li, Mengyu Guo, Bing Fei, Yanying Ren, Xiaojuan You, Yongwei Li
Summary: The escalating prevalence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a significant threat to global public health. This study explored the potential of piperine (PIP) as a efflux pump inhibitor for CRPA. The results showed that PIP enhanced the antibacterial activity of imipenem (IPM) and inhibited the MexAB-OprM efflux pump, indicating its potential as an efflux pump inhibitor for CRPA.
MICROBIAL PATHOGENESIS
(2023)
Article
Pharmacology & Pharmacy
Douweh Leyla Gbian, Abdelwahab Omri
Summary: This study evaluated the efficacy of liposomal gentamicin and erythromycin combined with PABN against P. aeruginosa isolates. The results showed that this combination significantly reduced the minimum inhibitory and bactericidal concentrations, inhibited biofilm formation, and affected virulence factor production and motility of the bacteria to various degrees.
Article
Biochemistry & Molecular Biology
Muyuan Chen, Xiaodong Shi, Zhili Yu, Guizhen Fan, Irina I. Serysheva, Matthew L. Baker, Ben F. Luisi, Steven J. Ludtke, Zhao Wang
Summary: This study presents the in situ structure of full-length Escherichia coli AcrAB-ToIC obtained by electron cryo-tomography, revealing the configuration and mechanism of this transmembrane efflux pump. The study suggests that AcrA acts as a bridge between the inner membrane and AcrB, enabling the transmission of drug-induced signals from AcrB to the ToIC channel within the pump.
Article
Biotechnology & Applied Microbiology
Chen Gao, Yin Chen, Xin Cheng, Yi Zhang, Yueyue Zhang, Ying Wang, Zhiyuan Cui, Yaling Liao, Ping Luo, Weihui Wu, Cheng Wang, Hao Zeng, Quanming Zou, Jiang Gu
Summary: This study identified a novel immunogenic epitope from the outer membrane protein PilY1 of Pseudomonas aeruginosa. A macrophage membrane-coated nanoparticle vaccine carrying this epitope induced an immune response and conferred protection in mice.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Critical Care Medicine
Stephen M. Stick, Alexia Foti, Robert S. Ware, Harm A. W. M. Tiddens, Barry S. Clements, David S. Armstrong, Hiran Selvadurai, Andrew Tai, Peter J. Cooper, Catherine A. Byrnes, Yvonne Belessis, Claire Wainwright, Adam Jaffe, Philip Robinson, Lisa Saiman, Peter D. Sly
Summary: The study found that early treatment with azithromycin in infants diagnosed with cystic fibrosis did not reduce the extent of structural lung disease at 36 months, but it did decrease airway inflammation and improve some clinical outcomes associated with cystic fibrosis lung disease.
LANCET RESPIRATORY MEDICINE
(2022)
Article
Medicine, Research & Experimental
Jing Qiao, Max Purro, Zhi Liu, May P. Xiong
Summary: A series of targeted poly(ethylene glycol)-desferrioxamine/gallium (PEG-DG) conjugates were evaluated for their antimicrobial activity, showing enhanced sensitivity of P. aeruginosa to vancomycin. The synergistic effect was observed with specific PEG-DG conjugates characterized by polymer length and molecular weight, contributing to improved antimicrobial efficacy against P. aeruginosa strains.
MOLECULAR PHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Xiaotuan Zhang, Changrui Qian, Miran Tang, Weiliang Zeng, Jingchun Kong, Cheng Fu, Chunquan Xu, Jianzhong Ye, Tieli Zhou
Summary: The aim of this study was to investigate the protective effect and mechanism of Klebsiella pneumoniae carbapenemase (KPC)-loaded outer membrane vesicles (OMVs) in Pseudomonas aeruginosa against imipenem treatment. OMVs loaded with KPC were isolated and purified from carbapenem-resistant Klebsiella pneumoniae (CRKP) and characterized using various assays. It was found that OMVs containing KPC protected P. aeruginosa from imipenem through antibiotic hydrolysis and induced carbapenem-resistant subpopulations.
DRUG RESISTANCE UPDATES
(2023)
Article
Medicine, General & Internal
Laura Macfarlane, Kartik Kumar, Thomas Scoones, Andrew Jones, Michael R. Loebinger, Robert Lord
Summary: Bronchiectasis is a heterogeneous and increasingly prevalent chronic pulmonary disease that is associated with significant morbidity. Clinically, patients may present differently and identifying underlying etiology is crucial in diagnosis. Treatment considerations include long-term antimicrobials, airway clearance methods, and other supportive management.
Article
Microbiology
Magnus Paulsson, Kasper Norskov Kragh, Yu-Ching Su, Linda Sandblad, Birendra Singh, Thomas Bjarnsholt, Kristian Riesbeck
Summary: The OmpA family proteins play crucial roles in cell morphology, membrane stability, and biofilm and outer membrane vesicle (OMV) formation in Pseudomonas aeruginosa. The lipoprotein from gene locus PA1041 was identified as a potential virulence factor that binds to peptidoglycan (PG) and influences the phenotype of the bacteria, leading to disordered biofilm formation. Mutants lacking this lipoprotein, designated as peptidoglycan-binding anchor (Pba), exhibited severe phenotypic changes, including enlarged periplasm spaces and increased release of OMV.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Cell & Tissue Engineering
Caixia Di, Yanshan Jiang, Lulu Li, Mengmeng Shi, Yinggang Zhu, Jing Zhang, Yuanlin Song, Xiao Su, Jieming Qu
Summary: Mesenchymal stem cells (MSCs) therapy attenuates LPS-induced acute lung injury and Pseudomonas aeruginosa (PA)-induced acute pneumonia, but the underlying molecular mechanisms are unclear. This study shows that PA-derived outer membrane vesicles (OMVs) induce mouse primary adipose tissue-derived mesenchymal stem cells (ASCs) to upregulate cyclic GMP-AMP synthase (cGAS) and express interleukin (IL)-7. Loss of cGAS-interferon (IFN)-beta axis abolishes the protective function of ASCs against PA-induced acute pneumonia. OMVs-delivered PA dsDNA activates cGAS-STING signaling pathway and increases IL-7 production via IFN-beta signaling in ASCs, which further amplifies IL-7 expression in lung epithelial cells.
Article
Cell Biology
Weizhong Chen, Ze-Hui Ren, Na Tang, Guoshi Chai, Hongyuan Zhang, Yifei Zhang, Jiacheng Ma, Zhaowei Wu, Xia Shen, Xingxu Huang, Guan-Zheng Luo, Quanjiang Ji
Summary: The STAGE method allows high-throughput Cas12k-guided mutagenesis in various microorganisms, facilitating the identification of essential genes and antibiotic-resistance-related factors. Due to its broad host range activity and easy programmability, this method can be widely adapted for rapid genome engineering and strain evolution in diverse microbial species.
Article
Microbiology
Albert Ruiz-Sorribas, Herve Poilvache, Francoise Van Bambeke
Summary: This study investigated the activity of different drugs against interkingdom biofilms using a three-species biofilm model. The results showed limited effectiveness of the drugs when used alone, but increased effects were observed when the drugs were used in combination, particularly against three-species biofilms. Additionally, different antibiotics showed better efficacy against different bacterial species. These findings were further confirmed by confocal microscopy images.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Chemistry, Medicinal
Gang Wang, Jean-Michel Brunel, Hector Rodriguez-Villalobos, Jean-Michel Bolla, Francoise Van Bambeke
Summary: NV716 can enhance the activity of antibiotics against difficult-to-treat Gram-negative bacteria by interacting with the bacterial outer membrane, resulting in increased accumulation of antibiotics inside bacteria. It can also increase the activity of antibiotics against intracellular infection and biofilms, without toxicity to eukaryotic cells at sub-MIC concentrations.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Alexia Chauzy, Grace Akrong, Vincent Aranzana-Climent, Jeremy Moreau, Laure Prouvensier, Helene Mirfendereski, Julien M. Buyck, William Couet, Sandrine Marchand
Summary: The inoculum effect, which refers to the reduction in antimicrobial activity at high bacterial counts, was confirmed in vivo in this study, which investigated the impact of inoculum size on polymyxin B efficacy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Infectious Diseases
Angele Modupe Dohou, Valentina Oana Buda, Loconon Achille Yemoa, Severin Anagonou, Francoise Van Bambeke, Thierry Van Hees, Francis Moise Dossou, Olivia Dalleur
Summary: The excessive use and misuse of antibiotics have a significant impact on the global numbers of antibiotic-resistant pathogens and commensal bacteria. In Benin, there are various problems with antibiotic use during caesarean sections, highlighting the need for a national policy to improve antibiotic usage.
Article
Mycology
Luc Deroche, Julien Buyck, Estelle Cateau, Blandine Rammaert, Sandrine Marchand, Kevin Brunet
Summary: K. bovina is a yeast species related to bloodstream infections, and its genome has not been published yet.
Article
Microbiology
Karin Santoni, David Pericat, Leana Gorse, Julien Buyck, Miriam Pinilla, Laure Prouvensier, Salimata Bagayoko, Audrey Hessel, Stephen Adonai Leon-Icaza, Elisabeth Bellard, Serge Mazeres, Emilie Doz-Deblauwe, Nathalie Winter, Christophe Paget, Jean-Philippe Girard, Christine T. N. Pham, Celine Cougoule, Renaud Poincloux, Mohamed Lamkanfi, Emma Lefrancais, Etienne Meunier, Remi Planes
Summary: This study identifies a new pyroptosis-inducing pathogen, Pseudomonas aeruginosa, and demonstrates that neutrophils are not universally resistant to Caspase-1-dependent pyroptosis.
Article
Infectious Diseases
Perrin Ngougni Pokem, Xavier Wittebole, Christine Collienne, Hector Rodriguez-Villalobos, Paul M. Tulkens, Laure Elens, Francoise Van Bambeke, Pierre-Francois Laterre
Summary: This study investigated the pharmacokinetics of temocillin in plasma and ascitic fluid, and performed dosing simulations. The current dosing regimen achieved the target concentration in plasma, but not in ascitic fluid. Adjusting the dosing regimen might allow for target concentration attainment in ascitic fluid, but further evaluation is needed for safety and efficacy.
Review
Pharmacology & Pharmacy
David De Bels, Evelyne Maillart, Francoise Van Bambeke, Sebastien Redant, Patrick M. Honore
Summary: Invasive candidiasis or candidemia is a severe global infection with high mortality, and therapeutic failure is common due to the emergence of resistant strains and new species. This review discusses the current antifungal drugs used for candidiasis and the advancements made in new formulations, derivatives, and repurposed drugs. The results from ongoing and future clinical trials will be crucial in determining the efficacy and interest of these drugs in the treatment of candidiasis.
EXPERT OPINION ON EMERGING DRUGS
(2022)
Article
Infectious Diseases
Maria Angeles Melendez-Carmona, Mikel Mancheno-Losa, Albert Ruiz-Sorribas, Irene Munoz-Gallego, Esther Viedma, Fernando Chaves, Francoise Van Bambeke, Jaime Lora-Tamayo
Summary: There is significant variability in the response of biofilm-embedded Staphylococcus aureus to levofloxacin and rifampicin. A lower range response, combined with other factors, could be responsible for treatment failure.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Biology
Gang Wang, Jean-Michel Brunel, Matthias Preusse, Negar Mozaheb, Sven D. Willger, Gerald Larrouy-Maumus, Pieter Baatsen, Susanne Haeussler, Jean-Michel Bolla, Francoise Van Bambeke
Summary: The polyaminoisoprenyl compound NV716 re-sensitizes Pseudomonas aeruginosa to antibiotics by permeabilizing the outer membrane and increases the activity of antibiotics on biofilms.
COMMUNICATIONS BIOLOGY
(2022)
Correction
Microbiology
Albert Ruiz-Sorribas, Herve Poilvache, Nur Hidayatul Nazirah Kamarudin, Annabel Braem, Francoise Van Bambeke
MICROBIOLOGY SPECTRUM
(2023)
Editorial Material
Infectious Diseases
Francoise Van Bambeke, Sebastian Wicha, Paul M. Tulkens, Markus Zeitlinger
Article
Microbiology
Romain Aubry, Julien Buyck, Laure Prouvensier, Jean-Winoc Decousser, Patrice Nordmann, Sebastian G. Wicha, Sandrine Marchand, Nicolas Gregoire
Summary: The study characterized the pharmacodynamic interaction over time between ceftazidime/avibactam and colistin against multidrug-resistant Klebsiella pneumoniae. While synergy or antagonism were observed under specific conditions, overall an additive interaction was found between the antibiotics. Simulations indicated that the combination at clinical concentrations should prevent the emergence of resistance.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
Frederic Peyrusson, Tiep Khac Nguyen, Tome Najdovski, Francoise Van Bambeke
Summary: This study investigates the effect of reactive oxygen species (ROS) on the dormancy depth of intracellular S. aureus persisters in host cells. It is found that host ROS can induce variable dormant states in persisters and the level of oxidative stress determines the capacity for resuscitation. The results highlight the importance of understanding the interplay between ROS, ATP depletion, and dormancy state in S. aureus infections.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Albert Ruiz-Sorribas, Herve Poilvache, Nur Hidayatul Nazirah Kamarudin, Annabel Braem, Francoise Van Bambeke
Summary: Biofilms are resistant to antimicrobials, but hydrolytic enzymes can reduce their biomass. Subtilisin A and lyticase are the most effective enzymes against interkingdom biofilms. Combining enzymes with antimicrobials further reduces the biomass.
MICROBIOLOGY SPECTRUM
(2022)