The biofilm matrix destabilizers, EDTA and DNaseI, enhance the susceptibility of nontypeable Hemophilus influenzae biofilms to treatment with ampicillin and ciprofloxacin

Cavaliere, R; Ball, JL; Turnbull, L; Whitchurch, CB

The biofilm matrix destabilizers, EDTA and DNaseI, enhance the susceptibility of nontypeable Hemophilus influenzae biofilms to treatment with ampicillin and ciprofloxacin

Cavaliere, R

Ball, JL Turnbull, L

Whitchurch, CB

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Publication Type:: Journal Article
Citation:: MicrobiologyOpen, 2014, 3 (4), pp. 557 - 567
Issue Date:: 2014-01-01

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Field	Value	Language
dc.contributor.author	Cavaliere, R https://orcid.org/0000-0002-4709-5081	en_US
dc.contributor.author	Ball, JL	en_US
dc.contributor.author	Turnbull, L https://orcid.org/0000-0002-9255-9033	en_US
dc.contributor.author	Whitchurch, CB https://orcid.org/0000-0003-2296-3791	en_US
dc.date.available	2014-05-28	en_US
dc.date.issued	2014-01-01	en_US
dc.identifier.citation	MicrobiologyOpen, 2014, 3 (4), pp. 557 - 567	en_US
dc.identifier.uri	http://hdl.handle.net/10453/32978
dc.description.abstract	Nontypeable Hemophilus influenzae (NTHi) is a Gram-negative bacterial pathogen that causes chronic biofilm infections of the ears and airways. The biofilm matrix provides structural integrity to the biofilm and protects biofilm cells from antibiotic exposure by reducing penetration of antimicrobial compounds into the biofilm. Extracellular DNA (eDNA) has been found to be a major matrix component of biofilms formed by many species of Gram-positive and Gram-negative bacteria, including NTHi. Interestingly, the cation chelator ethylenediaminetetra-acetic acid (EDTA) has been shown to reduce the matrix strength of biofilms of several bacterial species as well as to have bactericidal activity against various pathogens. EDTA exerts its antimicrobial activity by chelating divalent cations necessary for growth and membrane stability and by destabilizing the matrix thus enhancing the detachment of bacterial cells from the biofilm. In this study, we have explored the role of divalent cations in NTHi biofilm development and stability. We have utilized in vitro static and continuous flow models of biofilm development by NTHi to demonstrate that magnesium cations enhance biofilm formation by NTHi. We found that the divalent cation chelator EDTA is effective at both preventing NTHi biofilm formation and at treating established NTHi biofilms. Furthermore, we found that the matrix destablilizers EDTA and DNaseI increase the susceptibility of NTHi biofilms to ampicillin and ciprofloxacin. Our observations indicate that DNaseI and EDTA enhance the efficacy of antibiotic treatment of NTHi biofilms. These observations may lead to new strategies that will improve the treatment options available to patients with chronic NTHi infections. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT0571905
dc.relation	http://purl.org/au-research/grants/nhmrc/491126
dc.relation.ispartof	MicrobiologyOpen	en_US
dc.relation.isbasedon	10.1002/mbo3.187	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Biofilms	en_US
dc.subject.mesh	Haemophilus influenzae	en_US
dc.subject.mesh	Haemophilus Infections	en_US
dc.subject.mesh	Ampicillin	en_US
dc.subject.mesh	Edetic Acid	en_US
dc.subject.mesh	Ciprofloxacin	en_US
dc.subject.mesh	Deoxyribonuclease I	en_US
dc.subject.mesh	Anti-Bacterial Agents	en_US
dc.subject.mesh	Microbial Sensitivity Tests	en_US
dc.title	The biofilm matrix destabilizers, EDTA and DNaseI, enhance the susceptibility of nontypeable Hemophilus influenzae biofilms to treatment with ampicillin and ciprofloxacin	en_US
dc.type	Journal Article
utslib.citation.volume	4	en_US
utslib.citation.volume	3	en_US
utslib.for	060501 Bacteriology	en_US
utslib.for	0605 Microbiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	open_access
pubs.issue	4	en_US
pubs.publication-status	Published	en_US
pubs.volume	3	en_US

Abstract:

Nontypeable Hemophilus influenzae (NTHi) is a Gram-negative bacterial pathogen that causes chronic biofilm infections of the ears and airways. The biofilm matrix provides structural integrity to the biofilm and protects biofilm cells from antibiotic exposure by reducing penetration of antimicrobial compounds into the biofilm. Extracellular DNA (eDNA) has been found to be a major matrix component of biofilms formed by many species of Gram-positive and Gram-negative bacteria, including NTHi. Interestingly, the cation chelator ethylenediaminetetra-acetic acid (EDTA) has been shown to reduce the matrix strength of biofilms of several bacterial species as well as to have bactericidal activity against various pathogens. EDTA exerts its antimicrobial activity by chelating divalent cations necessary for growth and membrane stability and by destabilizing the matrix thus enhancing the detachment of bacterial cells from the biofilm. In this study, we have explored the role of divalent cations in NTHi biofilm development and stability. We have utilized in vitro static and continuous flow models of biofilm development by NTHi to demonstrate that magnesium cations enhance biofilm formation by NTHi. We found that the divalent cation chelator EDTA is effective at both preventing NTHi biofilm formation and at treating established NTHi biofilms. Furthermore, we found that the matrix destablilizers EDTA and DNaseI increase the susceptibility of NTHi biofilms to ampicillin and ciprofloxacin. Our observations indicate that DNaseI and EDTA enhance the efficacy of antibiotic treatment of NTHi biofilms. These observations may lead to new strategies that will improve the treatment options available to patients with chronic NTHi infections. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

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http://hdl.handle.net/10453/32978