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Menaquinone analogs inhibit growth of bacterial pathogens. Antimicrob Agents Chemother 2013 Nov;57(11):5432-7

Date

08/21/2013

Pubmed ID

23959313

Pubmed Central ID

PMC3811306

DOI

10.1128/AAC.01279-13

Scopus ID

2-s2.0-84885908612   25 Citations

Abstract

Gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. We initiated studies with four of these organisms to develop novel topical antibacterial agents that interfere with growth and exotoxin production, focusing on menaquinone analogs. Menadione, 1,4-naphthoquinone, and coenzymes Q1 to Q3 but not menaquinone, phylloquinone, or coenzyme Q10 inhibited the growth and to a greater extent exotoxin production of Staphylococcus aureus, Bacillus anthracis, Streptococcus pyogenes, and Streptococcus agalactiae at concentrations of 10 to 200 μg/ml. Coenzyme Q1 reduced the ability of S. aureus to cause toxic shock syndrome in a rabbit model, inhibited the growth of four Gram-negative bacteria, and synergized with another antimicrobial agent, glycerol monolaurate, to inhibit S. aureus growth. The staphylococcal two-component system SrrA/B was shown to be an antibacterial target of coenzyme Q1. We hypothesize that menaquinone analogs both induce toxic reactive oxygen species and affect bacterial plasma membranes and biosynthetic machinery to interfere with two-component systems, respiration, and macromolecular synthesis. These compounds represent a novel class of potential topical therapeutic agents.

Author List

Schlievert PM, Merriman JA, Salgado-Pabón W, Mueller EA, Spaulding AR, Vu BG, Chuang-Smith ON, Kohler PL, Kirby JR

Author

John Kirby PhD Chair, Center Associate Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Administration, Topical
Animals
Anti-Bacterial Agents
Bacillus anthracis
Bacterial Proteins
Cell Membrane
Drug Synergism
Exotoxins
Humans
Laurates
Monoglycerides
Rabbits
Reactive Oxygen Species
Repressor Proteins
Shock, Septic
Staphylococcal Infections
Staphylococcus aureus
Streptococcus agalactiae
Streptococcus pyogenes
Vitamin K 2