The Polycyclic Polyprenylated Acylphloroglucinol Antibiotic PPAP 23 Targets the Membrane and Iron Metabolism in Staphylococcus aureus

Frontiers in Microbiology
Huanhuan WangFriedrich Götz

Abstract

Recently, a series of endo-type B polycyclic polyprenylated acylphloroglucinols (PPAP) derivatives with high antimicrobial activities were chemically synthesized. One of the derivatives, PPAP 23, which showed high antimicrobial activity and low cytotoxicity, was chosen for further investigation of its bactericidal profiles and mode of action. PPAP 23 showed a better efficacy in killing methicillin resistant Staphylococcus aureus (MRSA) and decreasing the metabolic activity of 5-day-old biofilm cells than vancomycin. Moreover, S. aureus did not appear to develop resistance against PPAP 23. The antimicrobial mechanism of PPAP 23 was investigated by RNA-seq combined with phenotypic and biochemical approaches. RNA-seq suggested that PPAP 23 signaled iron overload to the bacterial cells because genes involved in iron transport were downregulated and iron storage gene was upregulated by PPAP 23. PPAP 23 affected the membrane integrity but did not induce pore formation; it inhibited bacterial respiration. PPAP 23 preferentially inhibited Fe-S cluster enzymes; it has a mild iron chelating activity and supplementation of exogenous iron attenuated its antimicrobial activity. PPAP 23 was more effective in inhibiting the growth of S. aureu...Continue Reading

References

Feb 1, 1991·The Biochemical Journal·O I AruomaM Dizdaroglu
Jan 1, 1987·Analytical Biochemistry·B Schwyn, J B Neilands
Jan 1, 1986·Infection·K SatoS Mitsuhashi
Feb 13, 2001·Journal of Microbiological Methods·B HerigstadJ Heersink
May 24, 2001·The Journal of Pharmacy and Pharmacology·J BarnesJ D Phillipson
Feb 8, 2003·Science·Sarkis K MazmanianOlaf Schneewind
Feb 15, 2005·Journal of Pharmaceutical and Biomedical Analysis·Frances LiuCatharina Y W Ang
Sep 14, 2006·Chemical Reviews·Roxana Ciochina, Robert B Grossman
Oct 24, 2006·Journal of Bacteriology·James T RiordanJohn E Gustafson
Aug 2, 2007·The Journal of Biological Chemistry·Jason C GriggMichael E P Murphy
Sep 7, 2007·Cell·Michael A KohanskiJames J Collins
Apr 26, 2008·Methods in Molecular Medicine·Howard M Shapiro
Jul 15, 2009·Recent Patents on Anti-infective Drug Discovery·Mathieu BalloucheChristine Baysse
Jun 7, 2011·Annual Review of Microbiology·Neal D Hammer, Eric P Skaar
Sep 29, 2011·Antimicrobial Agents and Chemotherapy·Nancy L ReederCharles W Saunders
Oct 5, 2011·Proceedings of the National Academy of Sciences of the United States of America·Peter SassHeike Brötz-Oesterhelt
Nov 24, 2011·Nature Chemistry·Nicole BiberBernd Plietker
Jul 4, 2012·Cellular Microbiology·Michael Otto
Aug 25, 2012·Frontiers in Cellular and Infection Microbiology·Rosmarie GauppGreg A Somerville
Aug 29, 2012·Antimicrobial Agents and Chemotherapy·Jongkon SaisingFriedrich Götz
Jan 7, 2015·Nature·Losee L LingKim Lewis
Aug 12, 2017·Genome Announcements·Isabelle CaldelariStefano Marzi
Feb 21, 2018·Chemical Reviews·Xing-Wei YangGang Xu
May 13, 2018·Biochemical and Biophysical Research Communications·John M C Gutteridge, Barry Halliwell

❮ Previous
Next ❯

Citations

Jan 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cassidy ScottChristian Lehmann

❮ Previous
Next ❯

Datasets Mentioned

BETA
PRJEB28806

Methods Mentioned

BETA
Fluorescence
fluorescence microscopy
X-ray
column chromatography
RNA-seq
Assay
chip

Software Mentioned

Qubit
R
edgeR package
Zeiss
ZEN

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Alabama Medicine : Journal of the Medical Association of the State of Alabama
T NagendranS Nagendran
Chemical Reviews
Roxana Ciochina, Robert B Grossman
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP
Yasmeen TajShahana Urooj Kazmi
Biological & Pharmaceutical Bulletin
Naomoto SuzukiTomofusa Tsuchiya
© 2022 Meta ULC. All rights reserved