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

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 th...

Full description

Saved in:

Bibliographic Details
Published in:	PloS one Vol. 12; no. 8; p. e0183263
Main Authors:	Uppu, Divakara S S M, Konai, Mohini M, Sarkar, Paramita, Samaddar, Sandip, Fensterseifer, Isabel C M, Farias-Junior, Celio, Krishnamoorthy, Paramanandam, Shome, Bibek R, Franco, Octávio L, Haldar, Jayanta
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 24-08-2017 Public Library of Science (PLoS)
Subjects:	Animal models Animals Anti-Bacterial Agents - pharmacology Antibacterial agents Antibiotics Bacteria Bacterial infections Biofilms Biology Biology and Life Sciences Carbapenemase Chemistry Colistin Colony Count, Microbial Dispersion Disruption Dosage and administration Drug resistance Drug Synergism Drug therapy Epidemiology Erythromycin Gram-negative bacteria Gram-Negative Bacteria - drug effects Gram-Negative Bacteria - isolation & purification Health aspects Health care Infections Informatics Klebsiella Laboratories Linezolid Lipopolysaccharides Macromolecules Medicine and Health Sciences Mice Microbial Sensitivity Tests Nehru, Jawaharlal (1889-1964) Peptides Pharmaceutical sciences Physical Sciences Polymers Potentiation Rifampin Risk factors Surgery Surgical site infections Vancomycin Wound infection Brazil
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Current address: Infectious Diseases Interdisciplinary Research Group (ID-IRG), Singapore-MIT Alliance for Research and Technology (SMART), Singapore
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0183263