Article
Biotechnology & Applied Microbiology
Ankita Nag, Sarika Mehra
Summary: Overexpression of efflux pumps, particularly SCO4121, in Streptomyces species contributes to multidrug resistance and increased tolerance against oxidative stress. The adjacent MarR regulator, SCO4122, positively regulates SCO4121 in response to various drugs and HOCl, highlighting novel mechanisms of antibiotic resistance in soil bacteria that may have implications for clinically important pathogens.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Manuel F. Varela, Jerusha Stephen, Deeksha Bharti, Manjusha Lekshmi, Sanath Kumar
Summary: Bacterial pathogens resistant to multiple antimicrobial agents through active efflux pose a serious threat to public health. This review discusses recent molecular studies focused on modulating the antimicrobial efflux transporters to restore the clinical efficacy of infectious disease chemotherapy.
Review
Biochemistry & Molecular Biology
Stephanie Sauve, Joseph Williamson, Adithya Polasa, Mahmoud Moradi
Summary: The major facilitator superfamily (MFS) of transporters consists of three classes of membrane transporters: symporters, uniporters, and antiporters. The conformational changes within the distinct transport cycles of MFS transporters are believed to follow the rocker-switch mechanism. This review compares the similarities and differences in conformational dynamics between symporters, uniporters, and antiporters of the MFS family using experimental and computational structural data.
Article
Microbiology
Nisha Mahey, Rushikesh Tambat, Nishtha Chandal, Dipesh Kumar Verma, Krishan Gopal Thakur, Hemraj Nandanwar
Summary: This study identified six clinically approved drugs that can inhibit the NorA efflux pump, showing synergism with fluoroquinolones and reducing antibiotic resistance in Staphylococcus aureus. These drugs also displayed anti-biofilm properties and efficacy in treating severe S. aureus infections in animal models.
MICROBIOLOGY SPECTRUM
(2021)
Article
Microbiology
Yingkun Wan, Miaomiao Wang, Edward Wai Chi Chan, Sheng Chen
Summary: Antibiotic tolerance is a key factor in recurrent and chronic bacterial infections, associated with the maintenance of the transmembrane proton motive force (PMF) by bacteria. Efflux pumps and transporters play a crucial role in the development and maintenance of tolerance, with specific genes identified to be essential in this process. Targeting these genes could lead to the design of antimicrobial agents to eradicate antibiotic tolerant persisters and prevent chronic and recurrent infections.
MICROBIOLOGY SPECTRUM
(2021)
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
Guoqing Zhai, Zhengyu Zhang, Changjiang Dong
Summary: This study systematically investigated the MFS Mdr transporter SotB in E. coli, revealing its mechanism for exporting L-arabinose, including key residues involved in substrate recognition and efflux. It also discovered that D-xylose may act as a competitive inhibitor hindering the binding of L-arabinose with SotB.
FRONTIERS IN MICROBIOLOGY
(2022)
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
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
Biology
Manuel F. Varela, Anely Ortiz-Alegria, Manjusha Lekshmi, Jerusha Stephen, Sanath Kumar
Summary: A phospholipid membrane acts as a barrier for the passage of molecules across living cells, but this barrier can be circumvented by transporter proteins. The major facilitator superfamily includes transporters found in all living organisms and plays important roles in various biological processes. The antiporter motif, known as motif C, is involved in the molecular mechanism of antimicrobial efflux.
Article
Biochemistry & Molecular Biology
Sichul Lee, Felipe K. Ricachenevsky, Tracy Punshon
Summary: Studies have shown that ZIF1 and ZIFL1 are important in zinc and iron homeostasis, with overlapping functions, while the role of ZIFL2 remains unclear.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Microbiology
Bahia Khalfaoui-Hassani, Petru-Iulian Trasnea, Stefan Steimle, Hans-Georg Koch, Fevzi Daldal
Summary: CcoA, a member of the bacterial copper importer subfamily CalT in the MFS, plays a crucial role in Cu uptake and cbb3-Cox production through specific residues and periplasm-exposed Cys residues. Elimination of certain Met residues in CcoA completely abolishes its activity, indicating at least one Met residue is required for function. Furthermore, a thiol:disulfide oxidoreduction cycle in CcoA is discovered to be important for its Cu import activity, providing insights into its molecular mechanism.
Article
Biochemistry & Molecular Biology
Ying Li, Xizhen Ge
Summary: The study investigated the natural mutations of the KmrA gene in Klebsiella pneumoniae and identified two variants that enhanced multidrug resistance. Through molecular dynamics simulations, it was revealed that these mutations increased drug export efficiency by strengthening the interactions between KmrA and water as well as the cell membrane, and promoting conformational changes.
Article
Cell Biology
Claudia Barata-Antunes, Gabriel Talaia, George Broutzakis, David Ribas, Pieter De Beule, Margarida Casal, Christopher J. Stefan, George Diallinas, Sandra Paiva
Summary: This study reveals novel roles of the N- and C-termini of the Jen1 protein in its biogenesis, plasma membrane stability, and transport activity. The results show that both termini are critical for the transport activity and endocytosis of Jen1, and that the interactions between these termini are dynamic and transport-dependent.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Qing Chen, Lu Lei, Caihong Liu, Yazhou Zhang, Qiang Xu, Jing Zhu, Zhenru Guo, Yan Wang, Qingcheng Li, Yang Li, Li Kong, Yunfeng Jiang, Xiujin Lan, Jirui Wang, Qiantao Jiang, Guoyue Chen, Jian Ma, Yuming Wei, Youliang Zheng, Pengfei Qi
Summary: The study identified FgMFS1 as an SA exporter in Fusarium graminearum, critical for its response to wheat endogenous SA and pathogenicity towards wheat. FgMFS1 was highly expressed during infection and upregulated by SA, indicating its role in responding to SA stress. Loss of function mutant of FgMFS1 showed enhanced sensitivity to SA, reduced pathogenicity towards wheat, and decreased DON production under SA stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Plant Sciences
Stephanie M. Forget, Andrew W. Robertson, David P. Overy, Russell G. Kerr, David L. Jakeman
JOURNAL OF NATURAL PRODUCTS
(2017)
Article
Pharmacology & Pharmacy
Steven R. Hall, Jay Toulany, Leah G. Bennett, Camilo F. Martinez-Farina, Andrew W. Robertson, David L. Jakeman, Kerry B. Goralski
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2017)
Article
Chemistry, Organic
S. M. Forget, Jungwook Na, N. E. McCormick, D. L. Jakeman
ORGANIC & BIOMOLECULAR CHEMISTRY
(2017)
Article
Chemistry, Multidisciplinary
Anna Ampaw, Madison Carroll, Jill von Velsen, Debabrata Bhattasali, Alejandro Cohen, Matthew W. Bowler, David L. Jakeman
Review
Chemistry, Multidisciplinary
Jeanna M. MacLeod, Stephanie M. Forget, David L. Jakeman
CANADIAN JOURNAL OF CHEMISTRY
(2018)
Article
Chemistry, Multidisciplinary
Jeanna M. MacLeod, Stephanie M. Forget, Camilo F. Martinez-Farina, David L. Jakeman
CANADIAN JOURNAL OF CHEMISTRY
(2018)
Article
Biotechnology & Applied Microbiology
Stephanie M. Forget, Andrew W. Robertson, Steven R. Hall, Jeanna M. MacLeod, David P. Overy, Russell G. Kerr, Kerry B. Goralski, David L. Jakeman
JOURNAL OF ANTIBIOTICS
(2018)
Article
Chemistry, Organic
Andrew W. Robertson, Jeanna M. MacLeod, Logan W. MacIntyre, Stephanie. M. Forget, Steven R. Hall, Leah G. Bennett, Hebelin Correa, Russell G. Kerr, Kerry B. Goralski, David L. Jakeman
JOURNAL OF ORGANIC CHEMISTRY
(2018)
Article
Multidisciplinary Sciences
Mackenzie Thornbury, Jacob Sicheri, Patrick Slaine, Landon J. Getz, Emma Finlayson-Trick, Jamie Cook, Caroline Guinard, Nicholas Boudreau, David Jakeman, John Rohde, Craig McCormick
Article
Chemistry, Physical
Kyle M. Stiers, Abigail C. Graham, Jian-She Zhu, David L. Jakeman, Jay C. Nix, Lesa J. Beamer
STRUCTURAL DYNAMICS-US
(2019)
Article
Chemistry, Organic
Jian-She Zhu, Kyle M. Stiers, Ebrahim Soleimani, Brandon R. Groves, Lesa J. Beamer, David L. Jakeman
JOURNAL OF ORGANIC CHEMISTRY
(2019)
Article
Chemistry, Multidisciplinary
Jian-She Zhu, Kyle M. Stiers, Sherany M. Winter, Anthony D. Garcia, Antoine F. Versini, Lesa J. Beamer, David L. Jakeman
Article
Chemistry, Organic
Stephanie M. Forget, Sydney B. Shepard, Ebrahim Soleimani, David L. Jakeman
JOURNAL OF ORGANIC CHEMISTRY
(2019)
Article
Endocrinology & Metabolism
Kyle M. Stiers, Reed P. Hansen, Bana A. Daghlas, Kelly N. Mason, Jian-She Zhu, David L. Jakeman, Lesa J. Beamer
JOURNAL OF INHERITED METABOLIC DISEASE
(2020)
Article
Biochemistry & Molecular Biology
Nicole E. McCormick, Stephanie M. Forget, Raymond T. Syvitski, David L. Jakeman
BIOCHEMISTRY AND CELL BIOLOGY
(2017)