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Defiance International

Study type: In vitro · Status: Evidence verified by machine against declared source

Mammalian histones facilitate antimicrobial synergy by disrupting the bacterial proton gradient and chromosome organization.

Nature communications · 2020

Study scale: a, b Growth profiles, measured by optical density, of E. coli and S. aureus treated with H2A in media containing a low (1 μM) magnesium (n = 33 for each condition) and b physiological (1 mM) magnesium (n = 11 for each condition). c Intracellular propidium iodide (PI) fluorescence intensities of H2A-treated E. coli in 1 μM and 1 mM concentrations of magnesium after 1-h treatment (n = 3 for each condition). d Growth profiles of E. coli (n = 18 for each condition) and S. aureus (n = 8 for each condition) treated with 10 μg/mL H2A, 2 μM LL-37, or both in medium containing 1 mM magnesium. e Intracellular propidium iodide (PI) fluorescence intensities of E. coli treated with 10 μg/mL H2A, 2 μM LL-37, both H2A and LL-37, 10 μg/mL kanamycin (Kan), or H2A and Kan, in medium containing 1 mM magnesium (n = 3 for each condition).

Abstract only: Open source record

Product or molecular entity relationships

  • LL-37: Exact entity relationship. Legacy citation custody associates this source with the catalog record; no product-relevance conclusion is implied.

Public plain-language summary

Some fields are not published, because the text held for them did not answer their heading. The published text is limited to the declared source and preserves reported uncertainty. It does not establish efficacy, safety, suitability, or evidence strength.

Research question

Histones and antimicrobial peptides have potent antimicrobial activity in NETs, but how the individual and combined effects of these components inhibit bacterial growth has not been determined11,12.

Study design

Not reported in the declared source.

Participants or experimental system

Not published. The text held for this field did not answer this heading, so nothing is shown here and nothing is substituted for it.

Study scale

a, b Growth profiles, measured by optical density, of E. coli and S. aureus treated with H2A in media containing a low (1 μM) magnesium (n = 33 for each condition) and b physiological (1 mM) magnesium (n = 11 for each condition). c Intracellular propidium iodide (PI) fluorescence intensities of H2A-treated E. coli in 1 μM and 1 mM concentrations of magnesium after 1-h treatment (n = 3 for each condition). d Growth profiles of E. coli (n = 18 for each condition) and S. aureus (n = 8 for each condition) treated with 10 μg/mL H2A, 2 μM LL-37, or both in medium containing 1 mM magnesium. e Intracellular propidium iodide (PI) fluorescence intensities of E. coli treated with 10 μg/mL H2A, 2 μM LL-37, both H2A and LL-37, 10 μg/mL kanamycin (Kan), or H2A and Kan, in medium containing 1 mM magnesium (n = 3 for each condition).

Intervention or exposure

More generally, treatment with H2A and the pore-forming antibiotic polymyxin B completely eradicates bacterial growth.

Comparator

Thus, levels of extracellular histones must be tightly controlled.

Outcomes examined

However, H2A-induced PI fluorescence could in principle reflect a bacterial response that induces cell death, where membrane permeabilization could be a secondary effect.

Key findings

H2A enhances AMP-induced pores, depolarizes the bacterial membrane potential, and impairs membrane recovery.

Limitations and uncertainty

The lack of complete growth inhibition was similarly observed in treatments with the bacteriostatic antibiotic chloramphenicol and bactericidal antibiotic kanamycin (Fig. 1f and Supplementary Fig. 1D), indicating that a lack of complete growth inhibition is not specific to H2A and LL-37 and may be a general property of antibiotic treatments in liquid cultures.

Product relevance and evidence boundary

This record is a published study, held here with its citation and review status. It is not a statement that any catalog item is effective, safe, or suitable for any use, and nothing in it is a dose or a protocol.

Evidence verified by machine against declared source. Verification is limited to the declared source and review scope. It does not mean independent replication or establish efficacy, safety, or suitability.