Article
Infectious Diseases
Abolfazl Dashtbani-Roozbehani, Melissa H. Brown
Summary: The increasing antimicrobial resistance in staphylococcal bacteria poses a major health threat globally, with decreased discovery of new antibiotics and increased use of sanitizers exacerbating the issue. Combining efflux pump inhibitors with current antibiotics to combat resistant staphylococci is a promising strategy. Future research on high-resolution structures of staphylococcal efflux pumps could lead to the development of more effective inhibitors for clinical use.
Review
Microbiology
Jerusha Stephen, Manjusha Lekshmi, Parvathi Ammini, Sanath H. Kumar, Manuel F. Varela
Summary: Infectious diseases caused by bacteria of the Vibrio genus have significant impacts on human health. The mechanisms of antimicrobial resistance in Vibrio spp. include biofilm formation and active antimicrobial efflux. Understanding these antimicrobial transport systems is important for studying Vibrio spp. pathogenesis and virulence.
Article
Microbiology
Zhemin Zhang, Christopher E. Morgan, Robert A. Bonomo, Edward W. Yu
Summary: The COVID-19 pandemic and the rise of antimicrobial-resistant bacterial infections have significantly impacted global health. Klebsiella pneumoniae, a Gram-negative pathogen, is a common cause of secondary bacterial infections in COVID-19 patients, with a mortality rate of 83%. The emergence of K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae, with a mortality rate of up to 71%, has raised public attention. We report the cryo-electron microscopy structures of K. pneumoniae AcrB, which plays a crucial role in drug resistance, in the absence and presence of erythromycin, providing insights into drug recognition and pump-drug interactions.
Article
Infectious Diseases
Stefany Plasencia-Rebata, Saul Levy-Blitchtein, Juana del Valle-Mendoza, Wilmer Silva-Caso, Isaac Pena-Tuesta, William Vicente Taboada, Fernando Barreda Bolanos, Miguel Angel Aguilar-Luis
Summary: The susceptibility of A. baumannii to fluoroquinolones and aminoglycosides was affected by the addition of PAβN, resulting in a decrease in resistance rates. Efflux pumps play a crucial role in the emergence of multidrug-resistant A. baumannii strains, and inhibiting them may be a useful adjunctive therapy for this pathogen.
Article
Chemistry, Medicinal
Lily A. Pisoni, Susan J. Semple, Sida Liu, Matthew J. Sykes, Henrietta Venter
Summary: The inhibition of efflux pumps is a promising approach to combating multidrug-resistant bacteria. We have developed a combined structure- and ligand-based model, using OpenEye software, for the identification of inhibitors of AcrB, the inner membrane protein component of the AcrAB-TolC efflux pump in Escherichia coli.
ACS INFECTIOUS DISEASES
(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
Biochemistry & Molecular Biology
Susumu Shinya, Kentaro Kawai, Naoki Kobayashi, Yukiko Karuo, Atsushi Tarui, Kazuyuki Sato, Masato Otsuka, Masaaki Omote
Summary: Drug efflux pump inhibitors were investigated to increase drug susceptibility of multidrug-resistant bacteria and restore the antimicrobial effect of fluoroquinolones. The lead inhibitor, derived from a known hMATE1 inhibitor, showed significant reduction in resistance and could act synergistically with antimicrobial drugs against infections caused by multidrug-resistant bacteria.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Fereshteh Amereh, Mohammad Reza Arabestani, Leili Shokoohizadeh
Summary: This study aimed to investigate the prevalence of OqxAB efflux pump genes and their relationship with antibiotic resistance, especially fluoroquinolones, in K. pneumoniae isolates. The expression levels of OqxAB genes and molecular typing were also evaluated. The results showed a high prevalence of multidrug-resistant K. pneumoniae isolates and widespread resistance to ciprofloxacin. The presence of OqxA and OqxB genes was significantly associated with resistance to ceftriaxone and chloramphenicol as well as ciprofloxacin, and the expression of the OqxA gene was higher in ciprofloxacin-resistant isolates.
IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES
(2023)
Review
Infectious Diseases
Nina Compagne, Anais Vieira Da Cruz, Reinke T. Mueller, Ruben C. Hartkoorn, Marion Flipo, Klaas M. Pos
Summary: Antimicrobial resistance (AMR) is a major public health problem that has caused an estimated 4.95 million deaths in 2019. The overuse of antibiotics has led to the development of bacterial strains that are resistant to known antibiotics. Multidrug efflux pumps, which are naturally expressed by Gram-negative bacteria, play a central role in AMR. This review focuses on eight families of efflux pump inhibitors (EPIs) that have shown activity against Escherichia coli or Pseudomonas aeruginosa, providing insights into their structure-activity relationships, synthesis, in vitro and in vivo activities, pharmacological properties, binding sites, and mechanisms of action.
Article
Infectious Diseases
Nayeong Kim, Joo-Hee Son, Kyeongmin Kim, Hyo-Jeong Kim, Minsang Shin, Je-Chul Lee
Summary: The study found that DksA plays a regulatory role in the antimicrobial susceptibility of Acinetobacter baumannii, with increment dksA mutant strains showing increased susceptibility to quinolones and tetracyclines but decreased susceptibility to aminoglycosides, and upregulation of efflux pump gene expression. In contrast, (p)ppGpp-deficient mutants downregulate efflux pump gene expression, indicating that (p)ppGpp and DksA have opposite roles in modulating antimicrobial susceptibility via efflux pump gene regulation in A. baumannii.
Article
Microbiology
Zhemin Zhang, Christopher E. Morgan, Robert A. Bonomo, Edward W. Yu
Summary: Acinetobacter baumannii, a highly antibiotic-resistant Gram-negative pathogen, is a significant global health threat. The presence of multidrug efflux pumps within the bacterium is a major cause of failure of drug-based treatments.
Article
Chemistry, Medicinal
Sandra Kovachka, Giuliano Malloci, Meline Simsir, Paolo Ruggerone, Stephane Azoulay, Isabelle Mus-Veteau
Summary: This review focuses on the biological evaluation and molecular mechanistic insights of inhibitors of the drug efflux activity of the Hedgehog receptor Patched1 (Ptch1). Ptch1 is known to be over-expressed in many types of cancers and plays a role in the resistance to chemotherapy of cancer cells. Inhibition of Ptch1 has been shown to improve the efficacy of chemotherapy without toxicity for healthy cells or potential side effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
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
Infectious Diseases
Song Zhang, Jun Wang, Juhee Ahn
Summary: The excessive use of antibiotics has led to the emergence of multidrug-resistant pathogens, posing challenges to clinical management and food control. The discovery of novel antibiotic potentiators can be useful for the treatment of bacterial infections. This review provides a comprehensive summary of advances in novel EPI discovery and the potential strategies for fighting antibiotic resistance.
Article
Microbiology
Srinivasan Vijaya Bharathi, Manjunath Venkataramaiah, Govindan Rajamohan
Summary: ST1816 and ST128 variants of A. baumannii, belonging to International clone II (GC2) with capsule types KL1:OCL8 and KL3:OCL1d, exhibited diverse virulome and resistome with coexistence of resistance-determining enzymes and multidrug efflux transporters. The presence of hotspot mutations in colistin resistance-conferring operons highlights the urgency of continued surveillance to monitor the emergence and dissemination of such novel ST variants in A. baumannii.
FRONTIERS IN MICROBIOLOGY
(2021)
