Beta-lactam-induced bacteriolysis of amino acid-deprived Escherichia coli is dependent on phospholipid synthesis.
The penicillin tolerance of amino acid-deprived relA+ Escherichia coli is attributed to the stringent response; i.e., relaxation of the stringent response suppresses penicillin tolerance. The beta-lactam-induced lysis of amino acid-deprived bacteria resulting from relaxation of the stringent response was inhibited by cerulenin, or by glycerol deprivation in the case of a gpsA mutant (defective in the biosynthetic sn-glycerol 3-phosphate dehydrogenase). Therefore, beta-lactam-induced lysis of amino acid-deprived cells was dependent on phospholipid synthesis. The lysis process during amino acid deprivation can be experimentally dissociated into two stages designated the priming stage (during which the interaction between the beta-lactam and the penicillin-binding proteins occurs) and the beta-lactam-independent lysis induction stage. Both stages were shown to require phospholipid synthesis. It has been known for some time that the inhibition of phospholipid synthesis is among the plethora of physiological changes resulting from the stringent response. These results indicate that the inhibition of peptidoglycan synthesis and the penicillin tolerance associated with the stringent response are both secondary consequences of the inhibition of phospholipid synthesis.
Rodionov
D G
DG
Department of Biochemistry and Microbiology, University of Victoria, British Columbia, Canada.
Pisabarro
A G
AG
de Pedro
M A
MA
Kusser
W
W
Ishiguro
E E
EE
D000667:Ampicillin / Q000494:pharmacology*; D001433:Bacteriolysis / Q000187:drug effects / Q000502:physiology*; D002569:Cerulenin / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D007532:Isoleucine / Q000172:deficiency*; D008025:Ligases; D008954:Models, Biological; D010403:Penicillin Resistance / Q000502:physiology; D010743:Phospholipids / Q000096:biosynthesis*
D010743:Phospholipids; D007532:Isoleucine; D002569:Cerulenin; D000667:Ampicillin; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases; D005990:Glycerol