DISCUSSION - Paper 22: Lin et al.

(2019) Cardiolipin Alters Rhodobacter sphaeroides Cell

Shape by Affecting Peptidoglycan Precursor Biosynthesis

Cardiolipin (CL) is widely studied for its general role in ATP synthesis and mitochondrial
functions in eukaryotes and the respiratory chain in both eukaryotes and prokaryotes (1, 2).
Recent studies provide evidences of its significant involvement in the pathogenicity of several
bacteria, such as in osmotic stress response in the enteropathogen E. coli (3), in the motility and
cell division of intracellular pathogen Shigella flexneri (4), in the cell wall fluidity and permeability
of P. aeruginosa (5) and so on. This study shows that CL is also involved in cell shape
maintenance of Rhodobacter shpaeroides, a non-pathogenic photosynthetic bacterium serving
as a model for peptidoglycan synthesis in pathogenic alphaproteobacteria such as chlamydias
and rickettsias.

The involvement of CL in a wide array of metabolic processes in pathogenic bacteria makes it

an interesting target for antibiotics. High-impact studies have demonstrated that antibiotics
targeting CL is a promising alternative for multi-drug resistant strains (5, 6, 8). For this reason, I
emphasized in the infographic the importance of CL as an antibiotic target. The development of
new antibiotics in an era of fighting antiobiotic-resistant pathogens may present as
counterproductive, so I added the advantages of CL-targeting drugs over current antibiotics
such as its direct involvement in development of drug resistance (6, 7, 9) and the use of CF-
mediated processes in new technologies for delivering antibiotics (10).

REFERENCES
1. Dudek J (2017) Role of Cardiolipin in Mitochondrial Signaling Pathways. Front. Cell Dev. Biol.
5:90. doi: 10.3389/fcell.2017.00090
2. Christian Sohlenkamp, Otto Geiger, Bacterial membrane lipids: diversity in structures and
pathways, FEMS Microbiology Reviews, Volume 40, Issue 1, January 2016, Pages 133–159,
https://doi.org/10.1093/femsre/fuv008
3. Romantsov, T., Guan, Z., & Wood, J. M. (2009). Cardiolipin and the osmotic stress responses of
bacteria. Biochimica et biophysica acta, 1788(10), 2092–2100.
doi:10.1016/j.bbamem.2009.06.010
4. Rossi RM, Yum L, Agaisse H, Payne SM. 2017. Cardiolipin synthesis and outer membrane
localization are required for Shigella flexneri virulence. mBio 8:e01199-17.
https://doi.org/10.1128/mBio.01199-17.
5. El Khoury, M., Swain, J., Sautrey, G. et al. Targeting Bacterial Cardiolipin Enriched
Microdomains: An Antimicrobial Strategy Used by Amphiphilic Aminoglycoside Antibiotics. Sci
Rep 7, 10697 (2017) doi:10.1038/s41598-017-10543-3
6. Lopalco, P., Stahl, J., Annese, C. et al. Identification of unique cardiolipin and monolysocardiolipin
species in Acinetobacter baumannii . Sci Rep 7, 2972 (2017) doi:10.1038/s41598-017-03214-w
7. Wipperman, M. F., Heaton, B. E., Nautiyal, A., Adefisayo, O., Evans, H., Gupta, R., … Glickman,
M. S. (2018). Mycobacterial Mutagenesis and Drug Resistance Are Controlled by
Phosphorylation- and Cardiolipin-Mediated Inhibition of the RecA Coprotease. Mol. Cell, 72(1),
152–161.e7. doi:10.1016/j.molcel.2018.07.037
8. Swain J, El Khoury M, Kempf J, Briée F, Van Der Smissen P, et al. (2018) Effect of cardiolipin on
the antimicrobial activity of a new amphiphilic aminoglycoside derivative on Pseudomonas
aeruginosa. PLOS ONE 13(8): e0201752. https://doi.org/10.1371/journal.pone.0201752
9. Jiang J, Bhuiyan MS, Shen H, … Howden BP, Lieschke GJ, and Peleg, AY. (2019). Antibiotic
resistance and host immune evasion in Staphylococcus aureus mediated by a metabolic
adaptation. PNAS. 116 (9) 3722-3727: https://doi.org/10.1073/pnas.1812066116
10. Marín-Menéndez, A., Montis, C., Díaz-Calvo, T., Carta, D., Hatzixanthis, K., Morris, C. J., …
Berti, D. (2017). Antimicrobial Nanoplexes meet Model Bacterial Membranes: the key role of
Cardiolipin. Scientific Reports, 7(1). doi:10.1038/srep41242