Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2006-9-11
pubmed:abstractText
Previously it was shown that the antimicrobial protein granulysin possesses potent membranolytic activity against Mycobacterium tuberculosis. Here we demonstrate that granF2 and G13, which are two short synthetic peptides derived from granulysin, inhibited the in vitro growth of clinical isolates of both multidrug resistant and drug susceptible strains of M. tuberculosis. Importantly, a particularly high activity against multidrug resistant M. tuberculosis correlated with a reduced growth rate compared to drug susceptible strains. A synergistic antibacterial effect of granF2 was further observed in combination with ethambutol, a compound with a documented effect on cell wall permeability. This finding suggests that granF2 and ethambutol exert their functions at different levels of the mycobacterial surface. Upon infection of macrophages in vitro, granF2 but not G13 efficiently reduced the intracellular growth of multidrug resistant M. tuberculosis in the presence of the pore-forming protein streptolysin O. The apoptotic function of granF2 apparently promoted destruction of host cells whereby the peptide gained access to and killed intracellular bacteria. Thus, a cost of resistance and a subsequent reduced fitness, measured as decreased growth among multidrug resistant strains of M. tuberculosis, could be associated with increased susceptibility to natural immune defense mechanisms, such as antimicrobial peptides of granulysin. However, a robust cell wall and the membrane of cells still provide physical shelter for the bacteria that may spare sensitive M. tuberculosis stains from being killed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1286-4579
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1985-93
pubmed:dateRevised
2010-9-1
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Enhanced susceptibility of multidrug resistant strains of Mycobacterium tuberculosis to granulysin peptides correlates with a reduced fitness phenotype.
pubmed:affiliation
Swedish Institute for Infectious Disease Control, Department of Bacteriology, 171 82 Solna, Sweden.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't