Do Mitochondria Use Efflux Pumps to Protect Their Ribosomes from Antibiotics?

Overview

Journal Microbiology (Reading)

Specialty Microbiology

Date 2023 Feb 7

PMID 36748523

Authors

Md Deen Islam

Brian D Harrison

Judy J-Y Li

Austein G McLoughlin

Deborah A Court

Affiliations

Soon will be listed here.

Abstract

Fungal environments are rich in natural and engineered antimicrobials, and this, combined with the fact that fungal genomes are rich in coding sequences for transporters, suggests that fungi are an intriguing group in which to search for evidence of antimicrobial efflux pumps in mitochondria. Herein, the range of protective mechanisms used by fungi against antimicrobials is introduced, and it is hypothesized, based on the susceptibility of mitochondrial and bacterial ribosomes to the same antibiotics, that mitochondria might also contain pumps that efflux antibiotics from these organelles. Preliminary evidence of ethidium bromide efflux is presented and several candidate efflux pumps are identified in fungal mitochondrial proteomes.

Citing Articles

Special collection to commemorate 40 years of antimicrobial efflux.

Kumar A, Blair J Microbiology (Reading). 2024; 170(6).

PMID: 38885034 PMC: 11261860. DOI: 10.1099/mic.0.001466.

Microbial Musings: Winter 2023.

Preston A Microbiology (Reading). 2023; 169(3).

PMID: 37171861 PMC: 10191382. DOI: 10.1099/mic.0.001331.

References

Cowen L, Sanglard D, Howard S, Rogers P, Perlin D . Mechanisms of Antifungal Drug Resistance. Cold Spring Harb Perspect Med. 2014; 5(7):a019752. PMC: 4484955. DOI: 10.1101/cshperspect.a019752. View

Khunweeraphong N, Kuchler K . Multidrug Resistance in Mammals and Fungi-From MDR to PDR: A Rocky Road from Atomic Structures to Transport Mechanisms. Int J Mol Sci. 2021; 22(9). PMC: 8124828. DOI: 10.3390/ijms22094806. View

Kim J, Cater R, Choy B, Mancia F . Structural Insights into Transporter-Mediated Drug Resistance in Infectious Diseases. J Mol Biol. 2021; 433(16):167005. PMC: 8292200. DOI: 10.1016/j.jmb.2021.167005. View

Margulis L . Symbiotic theory of the origin of eukaryotic organelles; criteria for proof. Symp Soc Exp Biol. 1975; (29):21-38. View

Hassan K, Liu Q, Henderson P, Paulsen I . Homologs of the Acinetobacter baumannii AceI transporter represent a new family of bacterial multidrug efflux systems. mBio. 2015; 6(1). PMC: 4337561. DOI: 10.1128/mBio.01982-14. View

Zhu Z, Zhang S, Liu H, Shen H, Lin X, Yang F . A multi-omic map of the lipid-producing yeast Rhodosporidium toruloides. Nat Commun. 2012; 3:1112. PMC: 3493640. DOI: 10.1038/ncomms2112. View

Flowers S, Barker K, Berkow E, Toner G, Chadwick S, Gygax S . Gain-of-function mutations in UPC2 are a frequent cause of ERG11 upregulation in azole-resistant clinical isolates of Candida albicans. Eukaryot Cell. 2012; 11(10):1289-99. PMC: 3485914. DOI: 10.1128/EC.00215-12. View

Omrane S, Sghyer H, Audeon C, Lanen C, Duplaix C, Walker A . Fungicide efflux and the MgMFS1 transporter contribute to the multidrug resistance phenotype in Zymoseptoria tritici field isolates. Environ Microbiol. 2015; 17(8):2805-23. DOI: 10.1111/1462-2920.12781. View

Keeping A, Deabreu D, DiBernardo M, Collins R . Gel-based mass spectrometric and computational approaches to the mitochondrial proteome of Neurospora. Fungal Genet Biol. 2010; 48(5):526-36. DOI: 10.1016/j.fgb.2010.11.011. View

10.

Kamper J, Kahmann R, Bolker M, Ma L, Brefort T, Saville B . Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis. Nature. 2006; 444(7115):97-101. DOI: 10.1038/nature05248. View

11.

Goncalves A, Silva N, Oliveira C, Kowbel D, Glass N, Kijjoa A . Transcription profiling of the Neurospora crassa response to a group of synthetic (thio)xanthones and a natural acetophenone. Genom Data. 2015; 4:26-32. PMC: 4535624. DOI: 10.1016/j.gdata.2015.02.001. View

12.

Young M . Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance. Front Mol Biosci. 2017; 4:74. PMC: 5702650. DOI: 10.3389/fmolb.2017.00074. View

13.

Jorgensen L, Heick T . Azole Use in Agriculture, Horticulture, and Wood Preservation - Is It Indispensable?. Front Cell Infect Microbiol. 2021; 11:730297. PMC: 8453013. DOI: 10.3389/fcimb.2021.730297. View

14.

Wolf K, Dujon B, SLONIMSKI P . Mitochondrial genetics. V. Multifactorial mitochondrial crosses involving a mutation conferring paromomycin-resistance in Saccharomyces cerevisiae. Mol Gen Genet. 1973; 125(1):53-90. DOI: 10.1007/BF00292983. View

15.

Martin J . Transport systems, intracellular traffic of intermediates and secretion of β-lactam antibiotics in fungi. Fungal Biol Biotechnol. 2020; 7:6. PMC: 7183595. DOI: 10.1186/s40694-020-00096-y. View

16.

Macino G, Tzagoloff A . Assembly of the mitochondrial membrane system: sequence analysis of a yeast mitochondrial ATPase gene containing the oli-2 and oli-4 loci. Cell. 1980; 20(2):507-17. DOI: 10.1016/0092-8674(80)90637-6. View

17.

Mourad A, Perfect J . Present and Future Therapy of Infections. J Fungi (Basel). 2018; 4(3). PMC: 6162641. DOI: 10.3390/jof4030079. View

18.

Di Bartolomeo F, Malina C, Campbell K, Mormino M, Fuchs J, Vorontsov E . Absolute yeast mitochondrial proteome quantification reveals trade-off between biosynthesis and energy generation during diauxic shift. Proc Natl Acad Sci U S A. 2020; 117(13):7524-7535. PMC: 7132131. DOI: 10.1073/pnas.1918216117. View

19.

Srinivasan V, Venkataramaiah M, Mondal A, Rajamohan G . Functional Characterization of AbeD, an RND-Type Membrane Transporter in Antimicrobial Resistance in Acinetobacter baumannii. PLoS One. 2015; 10(10):e0141314. PMC: 4619830. DOI: 10.1371/journal.pone.0141314. View

20.

Eicher T, Brandstatter L, Pos K . Structural and functional aspects of the multidrug efflux pump AcrB. Biol Chem. 2009; 390(8):693-9. DOI: 10.1515/BC.2009.090. View