2017
DOI: 10.1038/srep42141
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Targeting the molecular chaperone SlyD to inhibit bacterial growth with a small molecule

Abstract: Molecular chaperones are essential molecules for cell growth, whereby they maintain protein homeostasis. Because of their central cellular function, bacterial chaperones might be potential candidates for drug targets. Antimicrobial resistance is currently one of the greatest threats to human health, with gram-negative bacteria being of major concern. We found that a Cu2+ complex readily crosses the bacterial cell wall and inhibits SlyD, which is a molecular chaperone, cis/trans peptidyl prolyl isomerise (PPIas… Show more

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Cited by 13 publications
(18 citation statements)
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References 71 publications
(100 reference statements)
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“…This further supports our hypothesis that exposure to lactic acid and 2,3-butanediol alter physiology in clinically relevant ways. In particular, a down-regulated gene slyD , a molecular chaperone, is a key molecule involved in cell growth (Kumar and Balbach 2017 ). Additionally, fklB , a gene that has been shown to increase susceptibility of P. aeruginosa to B-lactams when mutated is also down-regulated (Alvarez-Ortega et al.…”
Section: Discussionmentioning
confidence: 99%
“…This further supports our hypothesis that exposure to lactic acid and 2,3-butanediol alter physiology in clinically relevant ways. In particular, a down-regulated gene slyD , a molecular chaperone, is a key molecule involved in cell growth (Kumar and Balbach 2017 ). Additionally, fklB , a gene that has been shown to increase susceptibility of P. aeruginosa to B-lactams when mutated is also down-regulated (Alvarez-Ortega et al.…”
Section: Discussionmentioning
confidence: 99%
“…4H,I), while residues Met1-Gln6, Lys11, Gln14, His24, Tyr43 and Leu100 remain almost unaffected. NMR intensities decreased for those residues, which are in close proximity to the paramagnetic Cu 2+ moiety, because of paramagnetic relaxation enhancement [19,29].…”
Section: Cu 2+ Complex Induces Intracellular Aggregation Of E6mentioning
confidence: 99%
“…-Zn 2+ complex interacted with the grooves of DNA -Zn 2+ There is a continuous effort to develop small molecules, including metal-based coordination complexes, for oncotherapy as well as novel anti-microbial agents [5][6][7][8].…”
Section: Highlightmentioning
confidence: 99%
“…Many of the currently developed coordination complexes exhibited cytotoxicity under in vitro conditions with either an apoptotic mode of action, or more often with an unknown mechanism, without knowing their cellular targets [12]. However, it is of medical interest to find coordination complexes/small molecules which are able to cross the cell wall/membrane barrier and exhibit cell toxicity by targeting the biomolecules responsible for specific housekeeping pathways [5,13].…”
Section: Highlightmentioning
confidence: 99%
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