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A new antibiotic kills pathogens without detectable resistance
Ling and Schneider et al, 2015Nature doi:10.1038/nature14098
99% of bacteria cannot be isolated from single cells on petri dishes.
in situ cultivation of bacteria with iChip
If an initial colony can be grown, 50% of bacterial can then be cultured on petri dishes.
uncultivated bacteria could be a source of novel compounds and antibiotics
dilute bacteria in molten agar
immerse iChip in agar to get1 cell per well
seal iChip with membranes
put iChip in soil to cultivatebacteria
screened 10,000 isolates for ability to inhibit S. aureus growth in petri dishes
16S tree of novel isolate, Eleftheria terrae
isolated active compound and determined its structure
serine
glutamine
isoleucine
serine
methyl-phenylalanine
isoleucine
isoleucine
enduracididine
isoleucine
alanine
threonine
teixobactin is a peptide of 11 amino acids
teixobactin encoded by 2 non-ribosomal peptide synthase genes
proteins synthesize a peptide independent of ribosome
domains in synthases are same order as amino acids in teixobactin
Teixobactin lyses S. aureus cultures
a. early log phaseb. late log phasec. culture clearingd. no resistance afterserial passage.
Teixobactin kills gram positive, but not gram negative bacteria
MIC=minimum inhibitory concentration
gram +
gram -
Teixobactin inhibits peptidoglycan synthesis similar to vancomycin
measure incorporation labeled precursors in S. aureus.gray (teixobactin), white (other antibiotic).Incorporation relative to ciproflaxin (DNA gyrase)Rifampicin (RNA polymerase)Vancomycin (peptidoglycan)Erythromycin (Ribosome)
Model of teixobactin action
teixobactin (T) produced by gram- bacterium that isprotected by outer membrane.
teixobactin (T) enters gram+ cell walland inhibits peptidoglycan synthesis by targeting lipid II (cell membrane anchored peptidoglycan (PG)precursor
Mice infected with S. aureus survive if given teixobactin
mice survive when given>0.25 mg/kg teixobactin
E. terrae is a new genus ofgram- Aquabacteria
"Teixobactin is the first new class of antibiotic announced in decades."-forbes.com