JAC Advance Access published online on January 28, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg099
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Welsh School of Pharmacy,
Cardiff University, Cardiff CF10 3XF
* Corresponding author. E-mail: russellD2{at}cardiff.ac.uk.
Received 13 May 2002
; revised 17 October 2002
; accepted 24 November 2002
The mechanisms of the mycobactericidal action of ortho-phthalaldehyde (OPA), glutaraldehyde (GTA)
and chlorhexidine diacetate (CHA) were investigated using mycobacterial
spheroplasts of two reference strains, Mycobacterium
chelonae NCTC 946, Mycobacterium abscessus NCTC 10882
and two GTA-resistant strains, M. chelonae Epping
and M. chelonae Harefield. Transmission electron
microscopy of the spheroplasts revealed an altered cell wall structure
compared with the parent cells. Structural alterations resulting
from the spheroplasting process were in part correlated to a loss
of lipid content. Low concentrations of CHA induced protein coagulation in M. chelonae NCTC 946 spheroplasts, which also exhibited
the highest loss of free non-polar lipids. Higher concentrations
of CHA were required to produce similar results to the other spheroplasts
investigated in which there was a less substantial decrease in lipid
content. OPA (0.5% w/v) readily penetrated the residual
cell wall and cytoplasmic membrane, producing significant protein
coagulation in M. chelonae NCTC 946. GTA (0.5% v/v)
induced a similar effect but to a lesser extent. Pre-treatment of
the spheroplasts with OPA and GTA and their subsequent suspension
in water demonstrated that GTA was a more potent cross-linking agent.
This protective effect of GTA results from extensive cross-linking
of amino and/or sulphydryl side-chain groups of proteins. The rapid
mycobactericidal effect of OPA probably arises from its more efficient
penetration across biological membranes. Mycobacterial spheroplasts
represented a useful cellular model with an altered cell wall permeability.
This study also showed the importance of the mycobacterial cell
wall in conferring intrinsic resistance to CHA.
Keywords: mechanism of action, cell wall, permeability
Effects of ortho-phthalaldehyde,
glutaraldehyde and chlorhexidine diacetate on Mycobacterium
chelonae and Mycobacterium abscessus strains
with modified permeability
2 School of Molecular and Medical Biosciences, Cardiff
University, Cardiff CF10 3TL
3 School
of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton
BN2 4GJ, UK
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