Recent evidence points towards a global increase in cases of multi drug and total drug resistant forms of Mycobacterium tuberculosis, suggesting that the mycobacterium is becoming resistant to the antibiotic regimen used to treat this infectious disease. New therapies are clearly needed, which may emerge from an improved understanding of the mechanisms by which M. tuberculosis avoids cellular clearance by lysosomes following engulfment in macrophage phagosomes. We now report that one of the common anti-tubercular drug targets, the so-called RND permease multi substrate pumps, is capable of secreting mycolic acids, a form of lipid enriched in these mycobacteria that make up part of the pathogens cell wall, as a way to inhibit phago- lysosome fusion and survive within the host cell. Our findings provide a mechanism that may explain how these cholesterol like mycolic acids may inhibit
Recent evidence points towards a global increase in cases of multi drug and total drug resistant forms of Mycobacterium tuberculosis, suggesting that the mycobacterium is becoming resistant to the antibiotic regimen used to treat this infectious disease. New therapies are clearly needed, which may emerge from an improved understanding of the mechanisms by which M. tuberculosis avoids cellular clearance by lysosomes following engulfment in macrophage phagosomes. We now report that one of the common anti-tubercular drug targets, the so-called RND permease multi substrate pumps, is capable of secreting mycolic acids, a form of lipid enriched in these mycobacteria that make up part of the pathogens cell wall, as a way to inhibit phago- lysosome fusion and survive within the host cell. Our findings provide a mechanism that may explain how these cholesterol like mycolic acids may inhibit
Chapter16: Adult And Pediatric Dosages Based On Body Surface Area
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Recent evidence points towards a global increase in cases of multi drug and total drug resistant forms of Mycobacterium tuberculosis, suggesting that the mycobacterium is becoming resistant to the antibiotic regimen used to treat this infectious disease. New therapies are clearly needed, which may emerge from an improved understanding of the mechanisms by which M. tuberculosis avoids cellular clearance by lysosomes following engulfment in macrophage phagosomes. We now report that one of the common anti-tubercular drug targets, the so-called RND permease multi substrate pumps, is capable of secreting mycolic acids, a form of lipid enriched in these mycobacteria that make up part of the pathogens cell wall, as a way to inhibit phago- lysosome fusion and survive within the host cell. Our findings provide a mechanism that may explain how these cholesterol like mycolic acids may inhibit the lysosomal protein NPC1, a lysosomal cholesterol transporter and the only mammalian member of the RND permease family, within the host macrophage. As M. tuberculosis utilises cholesterol as a food source for survival within the patient, our work suggests that secretion of mycolic acids outside the host cell followed by their uptake into host cell lysosomes, as previously described by others, may explain why granulomas within patient lungs that are full of necrotic cells and mycobacteria also contain such high levels of cholesterol.
With this information above, explain how the pathogenic micro-organism Mycobacterium tuberculosis secretes lipids called mycolic acids to cause the host macrophage to accumulate cholesterol?
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