INHIBITION OF THE GROWTH OF AGENTS OF THE PSITTACOSIS GROUP BYd-CYCLOSERINE AND ITS SPECIFIC REVERSAL BYd-ALANINE

Abstract

JULIUS E. OFFICER. Inhibition of the growth of agents of the psittacosis group by D-cycloserine and its specific reversal by D-alanine. J. Bacteriol. 85:707-711. 1963.-D-Cycloserine inhibited multiplication of four members of the psittacosis group in chick embryo yolk sac. D-Alanine reversed each inhibition. In infections with the agent of mouse pneumonitis, the most sensitive member of the psittacosis group tested, D-alanine competitively antagonized the growth inhibition produced bv D-cycloserine. Of a number of other potential reversing agents, only DL-alanyl-DLalanine reversed the effect of D-cycloserine on mouse pneumonitis agent. The significance of the susceptibility of the psittacosis group to D-cycloserine is discussed in light of the known mode of action of this antibiotic on bacteria. The growth-inhibiting effect of D-cycloserine (D-4-amino-3-isoxazolidone) on bacteria is competitively reversed by its structural analogue, D-alanine (Bondi, Kornblum, and Forte, 1957; Shockman, 1959; Morrison, 1962; Zygmunt, 1962). This relationship may be explained by the findings of Strominger, Ito, and Threnn (1960) that D-cycloserine inhibits both the alanine racemase and the D-alanyl-D-alanine synthetase of Staphylococcus aureus and that D-alanine competitively reverses the D-cycloserine inhibition of both reactions. Neuhaus and Lynch (1962) recently reported similar observations. Since D-1 A preliminary account of this work was presented at the Annual Meeting of the American Society for Microbiology, Kansas City, Mo.,

Characterization of Chlamydia MurC‐Ddl, a fusion protein exhibiting D‐alanyl‐D‐alanine ligase activity involved in peptidoglycan synthesis and D‐cycloserine sensitivity

“…Moulder et al first reported that DCS inhibited the growth of Chlamydia psittaci in chick embryo sacs (Moulder et al, 1963). This study also demonstrated that growth inhibition by DCS could be reversed in the presence of exogenous D-Ala or a racemic mixture of DL-Ala-DL-Ala but not L-Ala or other D-amino acids.…”

“…Although not used clinically, DCS is a substrate analogue of D-Ala that inhibits the function of Ddl proteins. For over 40 years, it has been known that the psittacosis group of Chlamydia is sensitive to DCS (Moulder et al, 1963). Like the psittacosis group, C. trachomatis is also sensitive to DCS (Table 2).…”

“…This conservation of essential amino acids extends to Chlamydia Ddl and suggests functionality and specificity of Chlamydia Ddl. Chlamydia are also sensitive to DCS, a substrate analogue of D-Ala that inhibits alanine racemase and D-Ala-D-Ala ligase (Moulder et al ., 1963;Lin and Moulder, 1966). In the absence of an alanine racemase, the sensitivity of Chlamydia to DCS predicts that Ddl is a functional D-Ala-D-Ala ligase and would be the target of DCS.…”

Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis

“…These gradients were centrifuged at 43,000 x g for 1 h at 4°C in an SW27 rotor. The EB bands, located at the 44/52% Renografin interface, were collected, diluted with 3 volumes of SPG, and then centrifuged at 30,000 x g for 30 min. The EB pellets were washed in SPG to remove residual Renografin.…”

Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis.

“…The exact nature of host-supplied factors and the environmental conditions for typical chlamydial development are unknown. However, deviations from the typical developmental cycle correspond significantly to a variety of alterations in growth conditions, including the presence of antibiotics (3,21,49,59,67,78,119) or host-elaborated factors (10, 66, 107) and deviations in the levels of essential nutrients (1, 25). These conditions generally delay RB maturation, inhibit differentiation to infectious EBs, and are associated with gross morphological alterations of RBs typified by markedly enlarged, atypical chlamydial forms.…”