JAC Advance Access published online on November 4, 2009
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkp409
Original research |
XF-70 and XF-73, novel antibacterial agents active against slow-growing and non-dividing cultures of Staphylococcus aureus including biofilms
1 Antimicrobial Research Centre and Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK 2 Destiny Pharma Limited, Science Park Square, Falmer, Brighton BN1 9SB, UK
Received 8 September 2009; returned 6 October 2009; revised 13 October 2009; accepted 14 October 2009
* Corresponding author. Tel: +44 113 233 5604; Fax: +44 113 233 5638; E-mail: i.chopra{at}leeds.ac.uk
Objectives: Slow-growing and non-dividing bacteria exhibit tolerance to many antibiotics. However, membrane-active agents may act against bacteria in all growth phases. We sought to examine whether the novel porphyrin antibacterial agents XF-70 and XF-73, which have rapid membrane-perturbing activity against Staphylococcus aureus, retained antistaphylococcal activity against growth-attenuated cells.
Methods: The killing kinetics of XF-70, XF-73 and various comparator agents against exponential phase cultures of S. aureus SH1000 were compared with effects on cells held at 4°C, non-growing cultures expressing the stringent response induced by mupirocin and bacteria in the stationary phase. Biofilms of S. aureus SH1000 were generated with the Calgary device to examine the activities of XF-70 and XF-73 under a further system exhibiting diminished bacterial growth.
Results: Cold culture, stringent response and stationary phase cultures remained susceptible to XF-70 and XF-73, which caused 
5 log reductions in viability over 2 h. During this period the most active comparator agents (chlorhexidine and cetyltrimethylammonium bromide) only promoted a 3 log drop in viability. XF-70 and XF-73 were also highly active against biofilms, with both agents exhibiting low biofilm MICs (1 mg/L) and minimum biofilm eradication concentrations (2 mg/L).
Conclusions: XF-70 and XF-73 remained highly active against various forms of slow-growing or non-dividing S. aureus. The results support the hypothesis that membrane-active agents may be particularly effective in eradicating slow- or non-growing bacteria and suggest that XF-70 and XF-73 could be utilized to treat staphylococcal infections where the organisms are only dividing slowly, such as biofilm-associated infections of prosthetic devices.
Key Words: drug action , porpyhrins , bactericidal activity