SETTING: Acquired immune deficiency syndrome (AIDS) patients have increased iron deposition in different tissues which may favour the growth of Mycobacterium avium, a common bacterial opportunist in these patients. OBJECTIVE: To test whether reducing the iron loads in macrophages in vitro and in vivo reduces M. avium proliferation. DESIGN: Mycobacterial proliferation was evaluated in vitro either in axenic media or cultured macrophages and in vivo in mice after manipulation of the iron status. RESULTS: Three different compounds--desferrioxamine (DFO), N,N'bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) and a 1-amino-3-(2-bipyridyl)isoquinoline derivative (VUF8514)--were found to inhibit the growth of M. avium in axenic medium. DFO and HBED were also active in inhibiting the intramacrophagic growth of M. avium, while the use of VUF8514 was prevented by its toxicity towards the host cell. Both DFO and HBED enhanced the mycobacteriostatic effect induced in bone marrow derived macrophages by interferon gamma. In vivo, an iron poor diet led to reduced M. avium proliferation whereas the intraperitoneal administration of either DFO or HBED had small effects as they impacted little on the iron status of mice. CONCLUSION: These results confirm that iron withholding is a means of inhibiting the growth of M. avium. In vitro data suggest that iron chelating compounds may be useful as adjunct therapy against M. avium, once their in vivo activity is optimized.
SETTING: Acquired immune deficiency syndrome (AIDS) patients have increased iron deposition in different tissues which may favour the growth of Mycobacterium avium, a common bacterial opportunist in these patients. OBJECTIVE: To test whether reducing the iron loads in macrophages in vitro and in vivo reduces M. avium proliferation. DESIGN: Mycobacterial proliferation was evaluated in vitro either in axenic media or cultured macrophages and in vivo in mice after manipulation of the iron status. RESULTS: Three different compounds--desferrioxamine (DFO), N,N'bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) and a 1-amino-3-(2-bipyridyl)isoquinoline derivative (VUF8514)--were found to inhibit the growth of M. avium in axenic medium. DFO and HBED were also active in inhibiting the intramacrophagic growth of M. avium, while the use of VUF8514 was prevented by its toxicity towards the host cell. Both DFO and HBED enhanced the mycobacteriostatic effect induced in bone marrow derived macrophages by interferon gamma. In vivo, an iron poor diet led to reduced M. avium proliferation whereas the intraperitoneal administration of either DFO or HBED had small effects as they impacted little on the iron status of mice. CONCLUSION: These results confirm that iron withholding is a means of inhibiting the growth of M. avium. In vitro data suggest that iron chelating compounds may be useful as adjunct therapy against M. avium, once their in vivo activity is optimized.
Authors: Heather L Briggs; Nicolein Pul; Rekha Seshadri; Mary J Wilson; Claudia Tersteeg; Kasi E Russell-Lodrigue; Masako Andoh; Andreas J Bäumler; James E Samuel Journal: Infect Immun Date: 2008-03-03 Impact factor: 3.441