Fusidic acid-resistant EF-G perturbs the accumulation of ppGpp
2000 (English)In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 37, no 1, 98-107 p.Article in journal (Refereed) Published
Reductions in growth rate caused by fusidic acidresistantEF-G mutants in Salmonella typhimuriumcorrelate strongly with increased mean cell size. This isunusual because growth rate and cell size normallycorrelate positively. The global transcription regulatormoleculeppGpp has a role in co-ordinating growth rateand division, and its basal level normally correlatesinversely with cell size at division.Weshowthat fusidicacid-resistant EF-G mutants have perturbed ppGppbasal levels during steady-state growth and perturbedinduced levels during starvation. One mutation, fusA1,associatedwith the slowest growth rate and largest cellsize, causes a reduction in the basal level of ppGpp toone-third of that found in the wild-type strain. OtherfusA mutants with intermediate or wild-type growthrates and cell sizes have either normal or increasedbasal levels of ppGpp. There is an inverse relationshipbetween the basal level of ppGppin vivo and the degreeto which translation dependent on mutant EF-G isinhibited by ppGpp in vitro. This enhanced interactionbetween mutant EF-G and ppGpp correlates with anincreased KM for GTP. Our results suggest that mutantEF-G modulates the production of ppGpp by the RelA(PSI) pathway. In conclusion, fusidic acid-resistant EFGmutations alter the level of ppGpp and break thenormal relationship between growth rate and cell sizeat division. It would not be surprising if other phenotypesassociated with these mutants, such as loss ofvirulence, were also related to perturbations in ppGpplevels effected through altered transcription patterns.
Place, publisher, year, edition, pages
Blackwell Science Ltd , 2000. Vol. 37, no 1, 98-107 p.
Microbiology in the medical area
IdentifiersURN: urn:nbn:se:uu:diva-38128DOI: 10.1046/j.1365-2958.2000.01967.xOAI: oai:DiVA.org:uu-38128DiVA: diva2:66027