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2016 ; 55
(1
): 128-34
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Molecular Analysis of Sarcoidosis Granulomas Reveals Antimicrobial Targets
#MMPMID26807608
Am J Respir Cell Mol Biol
2016[Jul]; 55
(1
): 128-34
PMID26807608
show ga
Sarcoidosis is a granulomatous disease of unknown cause. Prior molecular and
immunologic studies have confirmed the presence of mycobacterial virulence
factors, such as catalase peroxidase and superoxide dismutase A, within
sarcoidosis granulomas. Molecular analysis of granulomas can identify targets of
known antibiotics classes. Currently, major antibiotics are directed against DNA
synthesis, protein synthesis, and cell wall formation. We conducted molecular
analysis of 40 sarcoidosis diagnostic specimens and compared them with 33 disease
control specimens for the presence of mycobacterial genes that encode antibiotic
targets. We assessed for genes involved in DNA synthesis (DNA gyrase A [gyrA] and
DNA gyrase B), protein synthesis (RNA polymerase subunit ?), cell wall synthesis
(embCAB operon and enoyl reductase), and catalase peroxidase. Immunohistochemical
analysis was conducted to investigate the locale of mycobacterial genes such as
gyrA within 12 sarcoidosis specimens and 12 disease controls. Mycobacterial DNA
was detected in 33 of 39 sarcoidosis specimens by quantitative real-time
polymerase chain reaction compared with 2 of 30 disease control specimens
(P?0.001, two-tailed Fisher's test). Twenty of 39 were positive for three or
more mycobacterial genes, compared with 1 of 30 control specimens (P?0.001,
two-tailed Fisher's test). Immunohistochemistry analysis localized mycobacterial
gyrA nucleic acids to sites of granuloma formation in 9 of 12 sarcoidosis
specimens compared with 1 of 12 disease controls (P?0.01). Microbial genes
encoding enzymes that can be targeted by currently available antimycobacterial
antibiotics are present in sarcoidosis specimens and localize to sites of
granulomatous inflammation. Use of antimicrobials directed against target enzymes
may be an innovative treatment alternative.