Article
Medicine, Research & Experimental
Katerina Holasova, Bara Krizkovska, Lan Hoang, Simona Dobiasova, Jan Lipov, Tomas Macek, Vladimir Kren, Katerina Valentova, Tomas Ruml, Jitka Viktorova
Summary: Antibiotic resistance is a serious health problem, and the discovery of new antibiotics alone is no longer sufficient in combating multidrug-resistant infections. Adjuvant therapy and reducing bacterial virulence are gaining importance. Silymarin, a complex of flavonoids and flavonolignans, has a wide range of biological activities and can modulate drug resistance in cancer. This study tested eleven optically pure silymarin flavonolignans and found that some of them can reverse the multidrug resistance phenotype of Staphylococcus aureus and reduce its virulence.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Bhawandeep Kaur, Jeena Gupta, Sarika Sharma, Divakar Sharma, Sandeep Sharma
Summary: Staphylococcus aureus is a common pathogen causing various infections, with Methicillin-Resistant Staphylococcus aureus (MRSA) being particularly concerning. The primary antimicrobial resistance mechanisms in S. aureus involve efflux pumps and biofilm formation, with quorum sensing and drug efflux playing crucial roles. Efflux pump inhibitors (EPIs) have been identified as a promising approach to combat bacterial resistance, by inhibiting drug efflux mechanisms and transport of quorum sensing signalling molecules.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Gautam Kumar, Asha Kiran Tudu
Summary: Staphylococcus aureus (S. aureus) is a pathogen responsible for various infections with life-threatening complications. The misuse of antibiotics has led to the emergence of multidrug-resistant pathogens. Bacteria have developed mechanisms to avoid the effects of antibiotics. Inhibitors of multidrug efflux pumps are considered alternative therapeutic options. Natural products and their derived compounds can serve as NorA efflux pump inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Infectious Diseases
Jerusha Stephen, Fathima Salam, Manjusha Lekshmi, Sanath H. Kumar, Manuel F. Varela
Summary: This review article discusses the S. aureus-specific MFS multidrug efflux pump systems from a molecular mechanistic perspective, including structure-function relationships, modulation of antimicrobial resistance mediated by MFS drug efflux pumps, and direction for future investigation.
Article
Microbiology
Nishtha Chandal, Rushikesh Tambat, Ritu Kalia, Gautam Kumar, Nisha Mahey, Sanjay Jachak, Hemraj Nandanwar
Summary: In this study, a chemically synthesized indole derivative, SMJ-5, was found to be a potent NorA efflux pump inhibitor in Staphylococcus aureus. It increased the accumulation of ethidium bromide and norfloxacin, eradicated biofilm, and prolong the post-antibiotic effect when combined with ciprofloxacin. SMJ-5 also inhibited the staphyloxanthin virulence and showed enhanced bactericidal activity against S. aureus. Additionally, SMJ-5 indirectly inhibited the NorA efflux pump at the transcriptional level.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Nishtha Chandal, Rushikesh Tambat, Ritu Kalia, Gautam Kumar, Nisha Mahey, Sanjay Jachak, Hemraj Nandanwar
Summary: In this study, chemically synthesized indole derivatives were screened and a potent NorA efflux pump inhibitor, SMJ-5, was identified. The combination of SMJ-5 and ciprofloxacin showed enhanced bactericidal activity against S. aureus, and could eradicate S. aureus biofilm and prolong the post-antibiotic effect. SMJ-5 also inhibited staphyloxanthin virulence and NorA efflux pump at the transcriptional level indirectly.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Honghao Huang, Peng Wan, Xinyue Luo, Yixing Lu, Xiaoshen Li, Wenguang Xiong, Zhenling Zeng
Summary: Previous analysis has shown that overexpression of MepA is an exact mechanism involved in tigecycline resistance apart from the rpsJ mutation and is usually dependent on the mutant mepR. However, no research has evaluated the effects of diverse mutations discovered in TRSA in MepA. This study explores mutations in the mepA genes and identifies tigecycline resistance-associated mutations T29I, E287G, and T29I+E287G in MepA, demonstrating their role in promoting tigecycline efflux and providing genetic references for identifying TRSA.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
X. H. Yu, Z. H. Hao, P. L. Liu, M. M. Liu, L. L. Zhao, X. Zhao
Summary: The intensive and intermittent use of antibiotics leads to the rapid evolution of tolerance and acquisition of resistance. Efflux pumps are overexpressed in tolerant strains and contribute to resistance development. This study demonstrates the role of efflux pumps in the evolutionary trajectory from tolerance to resistance and suggests that inhibiting efflux pumps can delay the acquisition of resistance.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Gunther J. Staats, Samantha J. Mc Carlie, Charlotte E. Boucher-van Jaarsveld, Robert R. Bragg
Summary: This study aimed to identify the efflux transporters responsible for disinfectant resistance in a multidrug-resistant isolate Serratia sp. HRI compared to a susceptible Serratia sp. type strain. The results showed that the resistance capabilities of the resistant isolate significantly decreased after the addition of efflux pump inhibitors, confirming the important role of efflux pumps in the disinfectant resistance phenotype of bacteria.
Article
Infectious Diseases
Madalena Santos, Raquel Santos, Pedro Soeiro, Samuel Silvestre, Susana Ferreira
Summary: This study aimed to evaluate the ability of resveratrol to modulate norfloxacin resistance in Staphylococcus aureus. The results showed that resveratrol could modulate norfloxacin resistance by inhibiting the NorA efflux pump of S. aureus.
Article
Environmental Sciences
Xiaoqiang Liu, Jingru Zuo, Jiang Teng, Le Yang, Jingjing Guo, Lianjie Liu, Pei Li
Summary: This study investigated the prevalence and multidrug-resistant (MDR) phenotype of Staphylococcus aureus in raw milk samples and farm environments. The antimicrobial and antibiofilm activities of luteolin against MDR S. aureus were also explored. The results showed that luteolin can inhibit biofilm formation, reduce cell viability, and affect gene expression related to biofilm formation in S. aureus.
ENVIRONMENTAL POLLUTION
(2023)
Article
Microbiology
Grace Kaul, Abdul Akhir, Manjulika Shukla, Hasham Shafi, Ravikumar Akunuri, Gaurav Pawar, Mahammad Ghouse, Nanduri Srinivas, Sidharth Chopra
Summary: In this study, oxiconazole, a topical antifungal agent, was repurposed as a new treatment for multidrug-resistant Staphylococcus aureus infections. It exhibited potent activity against S. aureus and showed synergistic effects with the antibiotic gentamicin, resulting in superior therapeutic outcomes.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Casey L. Cazer, Lars F. Westblade, Matthew S. Simon, Reed Magleby, Mariana Castanheira, James G. Booth, Stephen G. Jenkins, Yrjo T. Grohn
Summary: Utilizing machine learning and graphical networks, this study quantified and visualized associations among resistance traits of Staphylococcus aureus isolates, revealing common associations between different classes of antimicrobial drugs. Association mining identified clinically important associations among antimicrobial resistance traits, providing insights for further investigation into resistance coselection.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Elisa Rampacci, Tommaso Felicetti, Giada Cernicchi, Valentina Stefanetti, Stefano Sabatini, Fabrizio Passamonti
Summary: One approach to treating antibiotic-resistant bacteria is to co-administer efflux pump inhibitors (EPIs) with antibiotics to break resistances connected with antibacterial efflux. In this study, ten compounds were evaluated for their ability to inhibit efflux and synergize with different antibiotics in Staphylococcus pseudintermedius. Hit compounds 1, 6, and 8 were considered the best EPIs for S. pseudintermedius. These findings provide valuable data for further optimization and development of EPIs for treating staphylococcal infections.
Article
Chemistry, Applied
Debora Feitosa Muniz, Cristina Rodrigues dos Santos Barbosa, Irwin Rose Alencar de Menezes, Erlanio Oliveira de Sousa, Raimundo Luiz Silva Pereira, Joao Tavares Calixto Junior, Pedro Silvino Pereira, Yedda M. L. S. de Matos, Roger H. S. da Costa, Cicera Datiane de Morais Oliveira-Tintino, Henrique Douglas Melo Coutinho, Jose Maria Barbosa Filho, Gabriela Ribeiro de Sousa, Jaime Ribeiro Filho, Jose Pinto Siqueira-Junior, Saulo Relison Tintino
Summary: This study evaluated the antibacterial activity of eugenol and its derivatives against Staphylococcus aureus NorA efflux pump, showing synergistic effects with some compounds. The findings suggest the potential use of eugenol derivatives in antibacterial drug development, particularly in strains carrying the NorA pump.
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)