Article
Microbiology
Punyawee Dulyayangkul, Naphat Satapoomin, Matthew B. Avison, Nisanart Charoenlap, Paiboon Vattanaviboon, Skorn Mongkolsuk
Summary: The study found that over-expression of MFS pumps in Pseudomonas aeruginosa can lead to over-expression of RND pumps, specifically MexXY, resulting in reduced susceptibility to aminoglycosides, quinolones, and paraquat. This cascade effect was found to be dependent on increased armZ expression. In addition, it was discovered that changes in paraquat susceptibility were independent of mexXY and armZ, indicating that paraquat is a substrate of MFS pumps Mfs1 and Mfs2.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Dana E. Harmon, Cristian Ruiz
Summary: This study reveals that the activity of AcrR, the main transcriptional regulator of the multidrug efflux pump AcrAB-TolC, is controlled by the antimicrobial ethidium bromide and polyamines produced by E. coli. AcrR regulates the expression of multiple genes involved in efflux and detoxification.
Article
Microbiology
Tobias Gundolf, Roland Kalb, Peter Rossmanith, Patrick Mester
Summary: The effective elimination of foodborne pathogens is crucial to the food processing industry, but the increasing spread of resistant strains is a major concern. This study explores the role of multidrug efflux pumps in the resistance of Escherichia coli and Salmonella enterica serovar Typhimurium to antimicrobial ionic liquids. The results highlight the importance of efflux pumps in IL toxicity studies and provide insights for the development of effective biocides against multidrug resistant bacteria.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Barbora Branska, Maryna Vasylkivska, Hana Raschmanova, Katerina Jureckova, Karel Sedlar, Ivo Provaznik, Petra Patakova
Summary: This study investigated the changes in active efflux during ABE fermentation and found fluctuations in efflux activity at different stages, suggesting that efflux pump activity is not constant throughout the fermentation process.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Microbiology
Seiji Yamasaki, Tomohiro Yoneda, Sota Ikawa, Mitsuko Hayashi-Nishino, Kunihiko Nishino
Summary: Fatty acid salts have bactericidal and bacteriostatic effects, but bacteria can adapt to their environment and overcome these effects. Bacterial efflux systems play a role in resistance to fatty acid salts. In this study, it was found that acrAB and tolC E. coli deletion strains were susceptible to fatty acid salts, while plasmids carrying acrAB, acrEF, mdtABC, or emrAB conferred resistance to the Delta acrAB mutant, indicating the complementary roles of these multidrug efflux pumps. Our data highlight the importance of bacterial efflux systems in E. coli resistance to fatty acid salts.
FRONTIERS IN MICROBIOLOGY
(2023)
Review
Microbiology
Shiela Chetri
Summary: Efflux pumps serve as an advanced defense system against antimicrobials, reducing drug concentration inside bacteria and expelling substances. This review provides a comprehensive overview of various efflux pump families and explores their potential applications. The review also discusses the diverse biological functions of efflux pumps, including their role in biofilm formation, quorum sensing, survival, virulence, and their potential relevance to antimicrobial resistance and antibiotic residue detection through associated genes/proteins. Furthermore, the use of plant-derived efflux pump inhibitors is extensively discussed.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ana C. J. de Araujo, Priscilla R. Freitas, Cristina R. dos Santos Barbosa, Debora F. Muniz, Jaime Ribeiro-Filho, Saulo R. Tintino, Jose P. S. Junior, Jose M. B. Filho, Gabriela R. de Sousa, Henrique D. M. Coutinho
Summary: Limonene, as an efflux pump inhibitor in Staphylococcus aureus strains RN-4220 and IS-58, showed enhanced antibacterial activity in association with ethidium bromide and antibiotics, indicating the inhibition of the MrsA and TetK pumps. Further studies are needed to characterize the molecular mechanisms associated with limonene-mediated efflux pump inhibition.
CURRENT DRUG METABOLISM
(2021)
Review
Infectious Diseases
Armel Jackson Seukep, Helene Gueaba Mbuntcha, Victor Kuete, Yindi Chu, Enguo Fan, Ming-Quan Guo
Summary: An effective response to antimicrobial resistance (AMR) requires a combination of prevention and treatment. Bacteria have developed strategies, such as over-expression of efflux pumps (EPs), to become resistant to antibiotics. Efforts are focused on developing resistance breakers, including natural plant extracts and alternative methods, to combat AMR.
Review
Chemistry, Multidisciplinary
Peter J. F. Henderson, Claire Maher, Liam D. H. Elbourne, Bart A. Eijkelkamp, Ian T. Paulsen, Karl A. Hassan
Summary: Bacterial multidrug efflux pumps play a crucial role in protecting bacteria from antimicrobials, but they also have other physiological functions. Studying the true physiological roles of these efflux pumps can help design more effective drugs and improve the efficiency of microbial drug production and commercial development.
Article
Pharmacology & Pharmacy
Cicera Datiane de Morais Oliveira-Tintino, Saulo Relison Tintino, Debora Feitosa Muniz, Cristina Rodrigues dos Santos Barbosa, Raimundo Luiz Silva Pereira, Ieda Maria Begnini, Ricardo Andrade Rebelo, Luiz Everson da Silva, Sandro Lucio Mireski, Michele Caroline Nasato, Maria Isabel Lacowicz Krautler, Pedro Silvino Pereira, Tereza Cristina Leal Balbino, Jose Galberto Martins da Costa, Fabiola Fernandes Galvao Rodrigues, Alexandre Magno Rodrigues Teixeira, Humberto Medeiros Barreto, Irwin Rose Alencar de Menezes, Henrique Douglas Melo Coutinho, Teresinha Goncalves da Silva
Summary: This study evaluated the antibacterial activity and inhibition of efflux mechanisms of a series of synthesized 1,8-naphthyridines sulfonamides against Staphylococcus aureus strains carrying MepA efflux pumps. The synthesized compounds showed no antibacterial activity but exhibited a favorable pharmacokinetic profile and potential inhibitory action on the MepA efflux pump, as demonstrated in molecular docking studies.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Review
Microbiology
Yinhuan Ding, Jingchen Hao, Weijia Xiao, Caihong Ye, Xue Xiao, Chunxia Jian, Min Tang, Guangrong Li, Jinbo Liu, Zhangrui Zeng
Summary: The article "The efficacy of Colistin-resistant strains and the mechanisms of multidrug resistance" discusses the contribution of efflux pumps and their related transcriptional regulators to Colistin resistance, as well as the reverse effect of efflux pump inhibitors. Previous studies have shown a complex regulatory relationship between efflux pumps and their transcriptional regulators, as well as LPS synthesis, transport, and modification. CCCP, NMP, and PA & beta;N can reverse Colistin resistance, highlighting the role of efflux pumps and their potential as adjuvant development. The contribution of efflux pumps to Colistin resistance may also be related to specific genetic backgrounds.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tanisha Teelucksingh, Laura K. Thompson, Shawna Zhu, Noah M. Kuehfuss, James A. Goetz, Stephanie E. Gilbert, Craig R. MacNair, Jennifer Geddes-McAlister, Eric D. Brown, Georgina Cox
Summary: Efflux pumps pose a challenge for the development of antibacterial agents. To overcome this challenge, researchers have generated a highly susceptible Escherichia coli strain lacking 35 efflux pumps, called Efflux KnockOut-35 (EKO-35). They have also constructed an efflux platform using this strain to study drug efflux characteristics, specificities of efflux pump inhibitors, and interplay between efflux pumps.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Napoleon D'Cunha, Mohammad Moniruzzaman, Keith Haynes, Giuliano Malloci, Connor J. Cooper, Enrico Margiotta, Attilio V. Vargiu, Muhammad R. Uddin, Inga Leus, Feng Cao, Jerry M. Parks, Valentin V. Rybenkov, Paolo Ruggerone, Helen Zgurskaya, John K. Walker
Summary: Antibiotic resistance is an increasingly urgent threat to human health, and multidrug efflux pumps are potential targets for combating this issue. The compound NSC-33353 has been identified as a potent inhibitor of efflux pumps, enhancing antibacterial activity in wild-type cells. Structural modifications of NSC-33353 have led to the development of compounds with improved inhibitory and substrate properties, offering insights into the duality of efflux substrate/inhibitor features and facilitating the development of new efflux pump inhibitors.
ACS INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Sreenath Dey, Sanket Rathod, Kondba Gumphalwad, Nikhil Yadav, Prafulla Choudhari, Eerappa Rajakumara, Rakesh Dhavale, Deepak Mahuli
Summary: Antibiotic resistance is a major global health crisis, and this study identifies potential chalcone molecules that interact with key multidrug efflux pumps of Escherichia coli. Computational analyses were conducted to evaluate binding affinities and pharmacokinetic properties of the chalcone compounds. The results demonstrate the potential of chalcones as promising candidates for targeting multidrug efflux pumps and overcoming antibiotic resistance.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Engineering, Environmental
Ting-Ting Zhu, Li-Jiao Tian, Sheng-Song Yu, Han-Qing Yu
Summary: The study discovered the significance of the Cd(II) efflux system in the biotransformation of Cd ions and selenite through engineered Escherichia coli strains. Suppressing the Cd(II) efflux system led to increased accumulation of Cd ions and higher production of CdSxSe1_x quantum dots (QDs), which exhibited similar viability to wild type cells and had potential applications in bio-imaging.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Infectious Diseases
Marta Hernandez-Garcia, Maria Garcia-Castillo, Sergio Garcia-Fernandez, Jose Melo-Cristino, Margarida F. Pinto, Elsa Goncalves, Valquiria Alves, Ana Raquel Vieira, Elmano Ramalheira, Luisa Sancho, Jose Diogo, Rui Ferreira, Tania Silva, Catarina Chaves, German Bou, Emilia Cercenado, Mercedes Delgado-Valverde, Antonio Oliver, Cristina Pitart, Jesus Rodriguez-Lozano, Nuria Tormo, Joao Romano, Leonor Passaro, Laura Paixao, Diego Lopez-Mendoza, Jazmin Diaz-Reganon, Rafael Canton
Summary: The study analyzed ceftolozane/tazobactam-susceptible or -resistant Pseudomonas aeruginosa clinical isolates from surveillance studies in Portugal and Spain. The most frequent MDR/XDR P. aeruginosa clones causing infections in Portuguese and Spanish ICU patients were found to be GES-13-CC235 and VIM type-CC175, respectively. Ceftolozane/tazobactam resistance was mainly due to carbapenemase production, although mutations in PBP-encoding genes may additionally be involved.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Chemistry, Physical
Kaushik Nath Bhaumik, Anasztazia Hetenyi, Gabor Olajos, Ana Martins, Reka Spohn, Lukacs Nemeth, Balazs Jojart, Petra Szili, Anett Dunai, Pramod K. Jangir, Lejla Daruka, Imre Foldesi, Diana Kata, Csaba Pal, Tamas A. Martinek
Summary: The novel PGLa analogues induce sustained membrane hyperpolarization and significantly reduce antibiotic resistance of multi-drug resistant bacteria. This antibiotic potentiation is mediated by altering cellular ion transport and manipulating bacterial membrane electrophysiology could be a valuable tool to overcome antimicrobial resistance.
MOLECULAR SYSTEMS DESIGN & ENGINEERING
(2022)
Article
Medicine, General & Internal
Rosario Serrao, Kamal Mansinho, Fernando Maltez, Nuno Marques, Alexandre Carvalho, Rosario Pazos, Alexandra Zagalo, Josefina Mendez, Isabel Neves, Joaquim Oliveira, Patricia Pacheco, Ricardo Correia de Abreu, Ana Claudia Miranda, Paula Camacho, Laura Paixao, Joana Almeida
Summary: This study aimed to characterize Portuguese HIV-infected patients who initiated raltegravir-based regimens, focusing on sociodemographics, clinical features, and treatment satisfaction. The results showed that most patients were male with an average age of 49, and around half had non-AIDS-related comorbidities at baseline.
ACTA MEDICA PORTUGUESA
(2022)
Article
Medicine, General & Internal
Claudia Nazareth, Ines Leitao, Ernestina Reis, Hugo Inacio, Filomena Martins, Elmano Ramalheira, Flavia Cunha, Carla Santos, Sara Lino, Hugo Moreira, Nadiya Kruptsala, Andrea Santos, Laura Paixao, Leonor Passaro, Monica Oleastro
Summary: This study aimed to characterize the epidemiology and clinical burden of Clostridioides difficile infection among hospitalized patients in Portugal. The study found that most patients were older and had risk factors, with recent antibiotic exposure being a common risk factor. The all-cause in-hospital mortality rate was higher among older patients.
ACTA MEDICA PORTUGUESA
(2022)
Editorial Material
Respiratory System
Sophia B. Georghiou, Timothy C. Rodwell, Alexei Korobitsyn, Said H. Abbadi, Kanchan Ajbani, Jan-Willem Alffenaar, David Alland, Nataly Alvarez, Sonke Andres, Elisa Ardizzoni, Alexandra Aubry, Rossella Baldan, Marie Ballif, Ivan Barilar, Erik C. Bottger, Soumitesh Chakravorty, Pauline M. Claxton, Daniela M. Cirillo, Inaki Comas, Chris Coulter, Claudia M. Denkinger, Brigitta Derendinger, Edward P. Desmond, Jurriaan E. M. de Steenwinkel, Keertan Dheda, Andreas H. Diacon, David L. Dolinger, Kelly E. Dooley, Matthias Egger, Maha R. Farhat, Lanfranco Fattorini, Iris Finci, Laure Fournier Le Ray, Victoria Furio, Ramona Groenheit, Tawanda Gumbo, Scott K. Heysell, Doris Hillemann, Harald Hoffmann, Po-Ren Hsueh, Yi Hu, Hairong Huang, Alamdar Hussain, Farzana Ismail, Kiyohiko Izumi, Tomasz Jagielski, John L. Johnson, Priti Kambli, Kone Kaniga, G. H. R. Eranga Karunaratne, Meenu Kaushal Sharma, Peter M. Keller, Ellis C. Kelly, Margarita Kholina, Mikashmi Kohli, Katharina Kranzer, Ian F. Laurenson, Jason Limberis, S-Y Grace Lin, Yongge Liu, Alexandre Lopez-Gavin, Anna Lyander, Diana Machado, Elena Martinez, Faisal Masood, Satoshi Mitarai, Nomonde R. Mvelase, Stefan Niemann, Vladyslav Nikolayevskyy, Florian P. Maurer, Matthias Merker, Paolo Miotto, Shaheed Omar, Ralf Otto-Knapp, Moises Palaci, Juan Jose Palacios Gutierrez, Sharon J. Peacock, Charles A. Peloquin, Jennifer Perera, Catherine Pierre-Audigier, Suporn Pholwat, James E. Posey, Therdsak Prammananan, Leen Rigouts, Jaime Robledo, Neesha Rockwood, Camilla Rodrigues, Max Salfinger, Marcos C. Schechter, Marva Seifert, Sarah Sengstake, Thomas Shinnick, Natalia Shubladze, Vitali Sintchenko, Frederick Sirgel, Sulochana Somasundaram, Timothy R. Sterling, Andrea Spitaleri, Elizabeth Streicher, Philip Supply, Erik Svensson, Elisa Tagliani, Sabira Tahseen, Akiko Takaki, Grant Theron, Gabriela Torrea, Armand Van Deun, Annelies Van Rie, Dick van Soolingen, Roger Vargas, Amour Venter, Nicolas Veziris, Cristina Villellas, Miguel Viveiros, Robin Warren, Shu'an Wen, Jim Werngren, Robert J. Wilkinson, Caie Yang, Tingting Zhang, Danila Zimenkov, Nazir Ismail, Thomas Schon, Claudio U. Koser, Soudeh Ehsani, Jakko van Ingen, F. Ferda Yilmaz
EUROPEAN RESPIRATORY JOURNAL
(2022)
Editorial Material
Infectious Diseases
A. L. Kritski, M. Viveiros, A. C. C. C. Arvalho
INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
(2022)
Article
Infectious Diseases
Anna Bateson, Julio Ortiz Canseco, Timothy D. McHugh, Adam A. Witney, Silke Feuerriegel, Matthias Merker, Thomas A. Kohl, Christian Utpatel, Stefan Niemann, Sonke Andres, Katharina Kranzer, Florian P. Maurer, Arash Ghodousi, Emanuele Borroni, Daniela Maria Cirillo, Maria Wijkander, Juan C. Toro, Ramona Groenheit, Jim Werngren, Diana Machado, Miguel Viveiros, Robin M. Warren, Frederick Sirgel, Anzaan Dippenaar, Claudio U. Koeser, Eugene Sun, Juliano Timm
Summary: The study reveals ancient differences in susceptibility to pretomanid among different lineages of Mycobacterium tuberculosis complex (MTBC) and recent emergence of resistance. The findings highlight the significance of considering global diversity of MTBC in clinical drug development and defining breakpoints for antimicrobial susceptibility testing.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Liliana Rodrigues, Renata Bento Cunha, Tatiana Vassilevskaia, Miguel Viveiros, Celso Cunha
Summary: This article provides an overview of the main developments in COVID-19 treatment and the contribution of drug repurposing. It also introduces a new drug repurposing strategy and lists 11 compounds that may be effective against COVID-19.
Article
Pharmacology & Pharmacy
Joaquim Trigo Marques, Catarina Frazao De Faria, Marina Reis, Diana Machado, Susana Santos, Maria da Soledade Santos, Miguel Viveiros, Filomena Martins, Rodrigo F. M. De Almeida
Summary: The increase in multidrug-resistant tuberculosis has made the challenge of ending this epidemic by 2030 even tougher. This has led to a search for more efficient antitubercular compounds, with a focus on isoniazid derivatives in this study. The study evaluates the cytotoxicity, binding to human serum albumin, and activity against resistant strains of Mycobacterium tuberculosis of these derivatives, showing promising results for their potential use as improved treatments.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Infectious Diseases
Sofia Santos Costa, Rute Ribeiro, Maria Serrano, Ketlyn Oliveira, Carolina Ferreira, Marta Leal, Constanca Pomba, Isabel Couto
Summary: This study investigated Staphylococcus aureus as a cause of skin and soft tissue infections in animals. It found a high frequency of MRSA strains and highlighted the circulation of clonal lineages between companion animals and humans.
Article
Infectious Diseases
Mariana Andrade, Ketlyn Oliveira, Catarina Morais, Patricia Abrantes, Constanca Pomba, Adriana E. Rosato, Isabel Couto, Sofia Santos Costa
Summary: This study reveals the frequent biofilm production by antimicrobial-resistant coagulase-positive staphylococci in companion animals, which is associated with a higher virulence potential and persistent or recurrent infections.
Article
Biochemistry & Molecular Biology
Carolina Ferreira, Patricia Abrantes, Sofia Santos Costa, Miguel Viveiros, Isabel Couto
Summary: This study identified the variability of norA within Staphylococcus aureus and its distribution among other staphylococci. It also demonstrated the applicability of a PCR-based algorithm to detect and differentiate norA alleles, and found the association of norA alleles with specific S. aureus clonal lineages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Infectious Diseases
Gabrielle Froberg, Florian P. Maurer, Erja Chryssanthou, Louise Fernstrom, Hanaa Benmansour, Samira Boarbi, Anne Torunn Mengshoel, Peter Michael Keller, Miguel Viveiros, Diana Machado, Margaret M. Fitzgibbon, Simone Mok, Jim Werngren, Daniela Maria Cirillo, Fernando Alcaide, Hanne-Leena Hyyrylainen, Alexandra Aubry, Sonke Andres, Darshaalini Nadarajan, Erik Svensson, John Turnidge, Christian G. Giske, Gunnar Kahlmeter, Emmanuelle Cambau, Jakko van Ingen, Thomas Schon
Summary: The study evaluated the minimum inhibitory concentration (MIC) distributions of non-tuberculous mycobacteria (NTM) to establish antimicrobial susceptibility testing (AST) breakpoints. MIC distributions for drugs against Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB) were collected from 12 laboratories. Epidemiological cut-off values (ECOFFs) and tentative ECOFFs (TECOFFs) were determined, highlighting the need for further method refinement in establishing clinical breakpoints for NTM.
CLINICAL MICROBIOLOGY AND INFECTION
(2023)
Editorial Material
Public, Environmental & Occupational Health
Paulo Ferrinho, Miguel Viveiros, Ines Fronteira
Review
Infectious Diseases
Allison M. Hitchcock, Wesley D. Kufel, Keri A. Mastro Dwyer, Eric F. Sidman
Summary: Lenacapavir is a novel HIV-1 treatment option for patients with multidrug-resistant (MDR) HIV-1 infection. It has a favorable pharmacokinetic profile and has shown good tolerability and efficacy in clinical trials.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)
Article
Infectious Diseases
Roberta Gagliardini, Alessandro Tavelli, Stefano Rusconi, Sergio Lo Caputo, Vincenzo Spagnuolo, Maria Mercedes Santoro, Andrea Costantini, Alessandra Vergori, Franco Maggiolo, Andrea Giacomelli, Giulia Burastero, Giordano Madeddu, Eugenia Quiros Roldan, Antonella d'Arminio Monforte, Andrea Antinori, Alessandro Cozzi-Lepri
Summary: This study evaluated multiple treatment failures to modern antiretroviral therapy in HIV-infected individuals and found that approximately 4% of them were difficult to treat. The difficult to treat group, compared to the non-difficult to treat group, was characterized by older age, higher prevalence of AIDS, lower CD4+ cell count, and higher risk of treatment failure.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)
