Bacterial metabolism and susceptibility to cell wall-active antibiotics

Keller, Megan; Dörr, Tobias

doi:10.1016/bs.ampbs.2023.04.002

Cited by 2 publications

(1 citation statement)

References 174 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondrial-targeted antioxidants are promising antibacterial agents whose mechanism of action is still surrounded by mystery and apparent cytotoxicity problems. Some features are already becoming clear, for example, the role of MDR pumps in resistance not only to antibiotics, but to substances that belong to protonophores [ 22 ], emphasizing the connection between bioenergetics, MDR pumps and antibiotic resistance [ 54 , 55 , 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Rhodamine 19 Alkyl Esters as Effective Antibacterial Agents

Nazarov,

Maximov,

Firsov

et al. 2024

IJMS

View full text Add to dashboard Cite

Mitochondria-targeted antioxidants (MTAs) have been studied quite intensively in recent years as potential therapeutic agents and vectors for the delivery of other active substances to mitochondria and bacteria. Their most studied representatives are MitoQ and SkQ1, with its fluorescent rhodamine analog SkQR1, a decyl ester of rhodamine 19 carrying plastoquinone. In the present work, we observed a pronounced antibacterial action of SkQR1 against Gram-positive bacteria, but virtually no effect on Gram-negative bacteria. The MDR pump AcrAB-TolC, known to expel SkQ1, did not recognize and did not pump out SkQR1 and dodecyl ester of rhodamine 19 (C12R1). Rhodamine 19 butyl (C4R1) and ethyl (C2R1) esters more effectively suppressed the growth of ΔtolC Escherichia coli, but lost their potency with the wild-type E. coli pumping them out. The mechanism of the antibacterial action of SkQR1 may differ from that of SkQ1. The rhodamine derivatives also proved to be effective antibacterial agents against various Gram-positive species, including Staphylococcus aureus and Mycobacterium smegmatis. By using fluorescence correlation spectroscopy and fluorescence microscopy, SkQR1 was shown to accumulate in the bacterial membrane. Thus, the presentation of SkQR1 as a fluorescent analogue of SkQ1 and its use for visualization should be performed with caution.

show abstract

Section: Discussionmentioning

confidence: 99%

Rhodamine 19 Alkyl Esters as Effective Antibacterial Agents

Nazarov,

Maximov,

Firsov

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

The role of Listeria monocytogenes PstA in β-lactam resistance requires the cytochrome bd oxidase activity

Tu,

Stevenson,

McCaslin

et al. 2024

J Bacteriol

View full text Add to dashboard Cite

c-di-AMP is an essential second messenger that binds and regulates several proteins of different functions within bacterial cells. Among those, PstA is a structurally conserved c-di-AMP-binding protein, but its function is largely unknown. PstA is structurally similar to PII signal transduction proteins, although it specifically binds c-di-AMP rather than other PII ligands such as ATP and α-ketoglutarate. In Listeria monocytogenes , we found that PstA increases β-lactam susceptibility at normal and low c-di-AMP levels, but increases β-lactam resistance upon c-di-AMP accumulation. Examining a PstA mutant defective for c-di-AMP binding, we found the apo form of PstA to be toxic for β-lactam resistance, and the c-di-AMP-bound form to be beneficial. Intriguingly, a role for PstA in β-lactam resistance is only prominent in aerobic cultures, and largely diminished under hypoxic conditions, suggesting that PstA function is linked to aerobic metabolism. However, PstA does not control aerobic growth rate, and has a modest influence on the tricarboxylic acid cycle and membrane potential—an indicator of cellular respiration. The regulatory role of PstA in β-lactam resistance is unrelated to reactive oxygen species or oxidative stress. Interestingly, during aerobic growth, PstA function requires the cytochrome bd oxidase (CydAB), a component of the respiratory electron transport chain. The requirement for CydAB might be related to its function in maintaining a membrane potential, or redox stress response activities. Altogether, we propose a model in which apo-PstA diminishes β-lactam resistance by interacting with an effector protein, and this activity can be countered by c-di-AMP binding or a by-product of redox stress. IMPORTANCE PstA is a structurally conserved c-di-AMP-binding protein that is broadly present among Firmicutes bacteria. Furthermore, PstA binds c-di-AMP at high affinity and specificity, indicating an important role in the c-di-AMP signaling network. However, the molecular function of PstA remains elusive. Our findings reveal contrasting roles of PstA in β-lactam resistance depending on c-di-AMP-binding status. We also define physiological conditions for PstA function during aerobic growth. Future efforts can exploit these conditions to identify PstA interaction partners under β-lactam stress.

show abstract

Bacterial metabolism and susceptibility to cell wall-active antibiotics

Cited by 2 publications

References 174 publications

Rhodamine 19 Alkyl Esters as Effective Antibacterial Agents

Rhodamine 19 Alkyl Esters as Effective Antibacterial Agents

The role of Listeria monocytogenes PstA in β-lactam resistance requires the cytochrome bd oxidase activity

Contact Info

Product

Resources

About