MP
Cryo-EM structure of the Pseudomonas aeruginosa MexY multidrug efflux pump.
Gregor WD, Maharjan R, Zhang Z, Chiaraviglio L, Sastry N, Cui M, Kirby JE, Yu EW.
mBio. 2025 Apr 9;16(4):e0382624.
doi: 10.1128/mbio.03826-24. Epub 2025 Mar 5.
PMID: 40042268.
Cryo-EM structure of MexY multidrug efflux pump from P. aeruginosa.
=> distinct conformational changes associated with substrate transport: shows how MexY coordinates with other components of the tripartite pump and binds diverse substrates.
Identification of potential therapeutics by targeting AcrB protein from AcrAB-TolC multidrug efflux pump of Escherichia coli: an in-silico exploration.
Alqarni MH, Alam A, Saad Al Oraby M, Foudah AI.
J Biomol Struct Dyn. 2025 Apr 10:1-16.
doi: 10.1080/07391102.2025.2487203. Online ahead of print.
PMID: 40205915.
in silico methods => potential inhibitors of the AcrB protein: computational starting point for developing new antibacterial agents. Virtual screening and MD reveal candidate molecules that may block substrate transport. The study provides structural and energetic insights into ligand binding.
Mg2+-dependent mechanism of environmental versatility in a multidrug efflux pump.
Russell Lewis B, Uddin MR, Kuo KM, Shah LMN, Harris NJ, Booth PJ, Hammerschmid D, Gumbart JC, Zgurskaya HI, Reading E.
Structure. 2025 Mar 6;33(3):552-565.e4.
doi: 10.1016/j.str.2024.12.012. Epub 2025 Jan 13.
PMID: 39809273.
This study explores how Mg²⁺ ions affect the versatility of a bacterial multidrug efflux pump (effect on AcrA, the PAP in AcrAB TolC). Biophysical and structural analyses show that Mg²⁺ binding alters protein conformational dynamics and substrate specificity. The pump’s flexibility is shown to be critical for adapting to environmental changes.
MprF from Pseudomonas aeruginosa is a promiscuous lipid scramblase with broad substrate specificity.
Hankins MTK, Parrag M, Garaeva AA, Earp JC, Seeger MA, Stansfeld PJ, Bublitz M.
Sci Adv. 2025 Apr 11;11(15):eads9135.
doi: 10.1126/sciadv.ads9135. Epub 2025 Apr 9.
PMID: 40203087.
MprF from P. aeruginosa = lipid scramblase with broad substrate specificity. Structural modeling and lipid flipping assays demonstrate its promiscuity across diverse lipid species. The study links this activity to bacterial resistance and membrane remodeling.
Membranes
Message hidden in α-helices – towards a better understanding of plant ABCG transporters’ multispecificity.
Biała-Leonhard W, Bigos A, Brezovsky J, Jasiński M.
Plant Physiol. 2025 Apr 12:kiaf146.
doi: 10.1093/plphys/kiaf146. Online ahead of print.
PMID: 40220341.
Investigation of the multispecificity of plant ABCG transporters by focusing on structural motifs in α-helices. Authors identify conserved patterns that may guide substrate recognition and selectivity.
Computational modeling => these motifs may influence the transport cycle.
Passive Transport across Cell Membranes beyond the Overton Rule: Insights from Solute Exchange in Vesicles and Molecular Dynamics of Atropisomers.
Cordeiro MM, Oliveira AC, Abreu PE, Arnaut LG, Moreno MJ, Loura LMS.
ACS Appl Mater Interfaces. 2025 Apr 10.
doi: 10.1021/acsami.4c22459. Online ahead of print.
PMID: 40210201.
This study challenges the Overton Rule* by analyzing passive solute transport across membranes using vesicle assays and MD. The authors examine atropisomers to explore how structural factors affect membrane permeability. Results indicate that membrane crossing depends on more than hydrophobicity, highlighting stereochemistry and dynamics. The findings call for a refined model of passive transport mechanisms.
- ”The Overton Rule states that entry of any molecule into a cell is governed by its lipid solubility. Overton’s studies led to the hypothesis that cell membranes are composed of lipid domains, which mediate transport of lipophilic molecules, and protein ‘pores’, which transport hydrophilic molecules” (Al-Awqati Q. One hundred years of membrane permeability: does Overton still rule? Nat Cell Biol. 1999 Dec;1(8):E201-2. doi: 10.1038/70230. PMID: 10587658).
Acyltransferases that Modify Cell Surface Polymers Across the Membrane.
Schultz BJ, Walker S.
Biochemistry. 2025 Apr 15;64(8):1728-1749.
doi: 10.1021/acs.biochem.4c00731. Epub 2025 Apr 2.
PMID: 40171682.
Review discussing acyltransferases that modify bacterial cell surface polymers through membrane-spanning mechanisms. These enzymes are crucial for assembling lipoteichoic acids and other structures influencing virulence and immune evasion. Structural insights into acyl donor recognition and membrane translocation are summarized.
Methods
Rigid enlargement of sybodies with antibody fragments for cryo-EM analyses of small membrane proteins.
Ackle F, Thavarasah S, Earp JC, Seeger MA.
Sci Rep. 2025 Mar 19;15(1):9460.
doi: 10.1038/s41598-025-92950-5.
PMID: 40108246.
Method to rigidify sybodies by fusing them to antibody fragments, enhancing cryo-EM analysis of small MPs. The enlarged complexes improve image alignment and resolution. This strategy maintains binding affinity while overcoming size limitations in structural studies.
MISO: Microfluidic protein isolation enables single particle cryo-EM structure determination from a single cell colony
Eluru G, De Gieter S, Schenck S, Stroobants A, Shrestha B, Erbel P, Brunner JD, Efremov RG
BioRxiv posted January 14, 2025.
https://doi.org/10.1101/2025.01.10.632437
MISO is an on-CHIP approach for proteins purification coupled to cryo-EM grids preparation, that uses hundred to thousand less biological material than conventional methods.
In this proof-of-concept paper, the authors use this approach to successfully solved the cryoEM structure of several model soluble and membrane proteins.
Microbio
Regulation, structure, and activity of the Pseudomonas aeruginosa MexXY efflux system.
Kavanaugh LG, Hinrichsen ME, Dunham CM, Conn GL.
Antimicrob Agents Chemother. 2025 Apr 7:e0182524.
doi: 10.1128/aac.01825-24. Online ahead of print.
PMID: 40192483.
Reviews on the MexXY efflux system in P. aeruginosa, focusing on its regulation, structural features, and role in antibiotic resistance. MexXY is inducible and shows substrate specificity distinct from other RND pumps. The authors highlight recent structural insights and the impact on therapeutic targeting.
Unlocking the Gates: A Novel Diagnostic Molecule for Quantifying Efflux Levels in Gram-Positive Bacteria.
Patil M, Munteanu T, Brasseur G, Ferreira C, Costa SS, Couto I, Athar M, Asunis E, Vargiu AV, Viveiros M, DiGiorgio C, Brunel F, Raimundo JM, Camplo M, Siri O, Bolla JM.
Adv Healthc Mater. 2025 Mar 11:e2404145.
doi: 10.1002/adhm.202404145. Online ahead of print.
PMID: 40066601.
A new diagnostic molecule is presented for quantifying efflux activity in Gram-positive bacteria. The compound fluoresces in proportion to efflux activity, allowing rapid phenotypic profiling. Its specificity and sensitivity were validated across multiple strains.
Efflux pump modulation by Montelukast and its roles in restoring antibiotic susceptibility in multidrug-resistant Staphylococcus aureus.
Ojha S, Sinsinwar S, Chatterjee P, Biswal S, Pradhan P, Beuria TK.
EBioMedicine. 2025 Apr;114:105658.
doi: 10.1016/j.ebiom.2025.105658. Epub 2025 Mar 28.
PMID: 40157128.
Montelukast (= anti-asthma drug), is shown to inhibit efflux pumps in multidrug-resistant S. aureus. It restores susceptibility to several antibiotics by interfering with efflux-mediated resistance. In vitro and in vivo assays confirm its adjuvant potential. This repurposing strategy offers a novel angle to tackle resistant infections.
Unveiling the potential of a novel drug efflux pump inhibitor to combat multidrug resistance in ESKAPEE pathogens, with a focus on Acinetobacter baumannii.
Brindangnanam P, Sawant AR, Ashokkumar K, Sriraghavan K, P S, Prashanth K, Coumar MS.
Microb Pathog. 2025 Jun;203:107513.
doi: 10.1016/j.micpath.2025.107513. Epub 2025 Mar 26.
PMID: 40147556.
Novel efflux pump inhibitor effective against Acinetobacter baumannii and other ESKAPEE pathogens. The compound enhances antibiotic activity and disrupts resistance mechanisms. Structural and functional assays confirm its mode of action. This study supports the development of efflux pump inhibitors as adjuncts in antimicrobial therapy.
The juxtamembrane domain of StkP is phosphorylated and influences cell division in Streptococcus pneumoniae.
Hamidi M, Nagarajan SN, Ravikumar V, Gueguen-Chaignon V, Laguri C, Freton C, Mijakovic I, Simorre J-P, Ravaud S, Grangeasse C.
mBio. 2025 Apr 8:e0379924.
doi: 10.1128/mbio.03799-24. Epub ahead of print.
PMID: 40197031.
Study of the phosphorylation of the juxtamembrane domain of StkP, a key serine/threonine kinase in Streptococcus pneumoniae. Authors show that this modification regulates cell division by affecting protein-protein interactions. Structural and mutational analyses highlight the role of phosphorylation in modulating StkP function.
Miscellaneous
Microbes can capture carbon and degrade plastic – why aren’t we using them more?
Rappuoli R, Nguyen NK, Bloom DE, Brooke C, Burckhardt RM, Dangour AD, Egamberdieva D, Gronvall GK, Lawley TD, Lennon JT, Morhard R, Mukhopadhyay A, Peixoto R, Silver PA, Stein LY.
Nature. 2025 Mar;639(8056):864-866.
doi: 10.1038/d41586-025-00875-w.
PMID: 40133617.
Interventions involving bacteria or fungi could help to sequester greenhouse gases, create more sustainable products and clean up pollution — in ways that are economically viable and safe.
How to protect the gut from antibiotics
https://www.nature.com/articles/d41586-025-00477-6
Antibiotics save lives, but they also wreak havoc on the beneficial bacteria that inhabit the human gut. Researchers are pursuing several strategies to protect these helpful microbes. One company has genetically engineered bacteria and nutritional yeast to carry an enzyme that breaks down amoxicillin in the gut without affecting the antibiotic’s ability to fight infection elsewhere in the body. Other scientists have found that high- fibre diets allay antibiotics’ effects on the gut by changing how intestinal microbes metabolize nutrients.
The secrets to a healthier, happier lab
Can mindfulness, meditation and other tools designed to boost well-being make a difference?
A Nature careers podcast:
https://www.nature.com/articles/d41586-025-00538-w
The unknown bounds of AI’s energy hunger
The appetite for electricity to power artificial intelligence (AI) systems is certainly growing, but by how much? And how much is too much? In the US state of Virginia — known as the data-centre capital of the world — communities are worried that facilities could drive up costs for residents and strain the area’s power infrastructure beyond its capacity. The same questions are being asked all over the world, and they have researchers struggling to answer. “The real problem is that we’re operating with very little detailed data and knowledge of what’s happening,” says Jonathan Koomey, who has studied the energy use of computing for more than 30 years. Companies are close-lipped about what they consume, and “nobody has any idea what data centres, either AI or conventional, will use even a few years from now”.