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Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria

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Title Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria
Not Available
 
Creator Uppu DSSM
Konai MM
Sarkar P
Samaddar S
Fensterseifer ICM
Junior CF
Krishnamoorthy P
shome BR
Franco OL
Haldar J
 
Subject membrane active macromolecules, Gram negative bacteria
 
Description Not Available
Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin) to biofilms of Gram-negative bacteria. These molecules eliminate planktonic bacteria that are liberated after dispersion of biofilms (dispersed cells). The membrane-active mechanism of these molecules forms the key for potentiating the established antibiotics. Further, we demonstrate that the combination of macromolecules and antibiotics significantly reduces bacterial burden in mouse burn and surgical wound infection models caused by Acinetobacter baumannii and Carbapenemase producing Klebsiella pneumoniae (KPC) clinical isolate respectively. Colistin, a well-known antibiotic targeting the lipopolysaccharide (LPS) of Gram-negative bacteria fails to kill antibiotic tolerant cells and dispersed cells (from biofilms) and bacteria develop resistance to it. On the contrary, these macromolecules prevent or delay the development of bacterial resistance to known antibiotics. Our findings emphasize the potential of targeting the bacterial membrane in antibiotic potentiation for disruption of biofilms and suggest a promising strategy towards developing therapies for topical treatment of Gram-negative infections.
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Date 2018-09-19T06:57:28Z
2018-09-19T06:57:28Z
2017-08-24
 
Type Research Paper
 
Identifier Uppu DSSM, Konai MM, Sarkar P, Samaddar S, Fensterseifer ICM, Farias-Junior C, et al. (2017) Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria. PLoS ONE 12(8): e0183263.
1932-6203
http://krishi.icar.gov.in/jspui/handle/123456789/7003
 
Language English
 
Relation Not Available;
 
Publisher Public Library of Science Publications