M S Gomes1, J R Boelaert, R Appelberg. 1. Laboratory of Microbiology and Immunology of Infection, Institute for Molecular and Cell Biology, University of Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
Abstract
BACKGROUND: Acquired immunodeficiency syndrome (AIDS) patients exhibit alterations in the metabolism of iron that lead to increased deposition of this element in the tissues. Such alterations may underlie an increased susceptibility of AIDS patients to mycobacterial infections, namely by Mycobacterium avium. OBJECTIVES: The understanding of the role of iron metabolism during M. avium infections in mouse models may allow the design of new therapies based on the manipulation of iron stores. STUDY DESIGN: In vitro macrophage cultures and in vivo mouse studies of iron depletion and iron overload are used to assess mycobacterial multiplication and testing of the efficacy of iron depletion strategies such as the use of iron chelators. RESULTS AND CONCLUSIONS: The levels of iron loading of macrophages in vitro or in vivo affect the growth of M. avium. The currently available iron chelators have poor efficacy in depleting the macrophage iron stores and, therefore, have a poor impact on the infection. Therefore, newer drugs are required that may be used in the context of in vivo infections such as in the case of affected AIDS patients.
BACKGROUND: Acquired immunodeficiency syndrome (AIDS) patients exhibit alterations in the metabolism of iron that lead to increased deposition of this element in the tissues. Such alterations may underlie an increased susceptibility of AIDSpatients to mycobacterial infections, namely by Mycobacterium avium. OBJECTIVES: The understanding of the role of iron metabolism during M. aviuminfections in mouse models may allow the design of new therapies based on the manipulation of iron stores. STUDY DESIGN: In vitro macrophage cultures and in vivo mouse studies of iron depletion and iron overload are used to assess mycobacterial multiplication and testing of the efficacy of iron depletion strategies such as the use of iron chelators. RESULTS AND CONCLUSIONS: The levels of iron loading of macrophages in vitro or in vivo affect the growth of M. avium. The currently available iron chelators have poor efficacy in depleting the macrophage iron stores and, therefore, have a poor impact on the infection. Therefore, newer drugs are required that may be used in the context of in vivo infections such as in the case of affected AIDSpatients.
Authors: Maher Y Abdalla; Barbara L Switzer; Christopher H Goss; Moira L Aitken; Pradeep K Singh; Bradley E Britigan Journal: Antimicrob Agents Chemother Date: 2015-06-01 Impact factor: 5.191
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