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Amino acid deprivation and central carbon metabolism regulate the production of outer membrane vesicles and tubes by Francisella
Author(s) -
Sampath Vinaya,
McCaig William D.,
Thanassi David G.
Publication year - 2018
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13897
Subject(s) - francisella tularensis , francisella , tularemia , biology , bacterial outer membrane , virulence , microbiology and biotechnology , cysteine , mutant , amino acid , vesicle , biochemistry , gene , escherichia coli , membrane , enzyme
Summary Francisella tularensis is a highly virulent Gram‐negative bacterial pathogen that causes the zoonotic disease tularemia. F. novicida , a model tularemia strain, produces spherical outer membrane vesicles (OMV), as well as novel tubular vesicles and extensions of the cell surface. These OMV and tubes (OMV/T) are produced in a regulated manner and contain known virulence factors. Mechanisms by which bacterial vesicles are produced and regulated are not well understood. We performed a genetic screen in F. novicida to decipher the molecular basis for regulated OMV/T formation, and identified both hypo‐ and hyper‐vesiculating mutants. Mutations in fumA and tktA , involved in central carbon metabolism, and in FTN_0908 and FTN_1037, of unknown function, resulted in severe defects in OMV/T production. Cysteine deprivation was identified as the signal that triggers OMV/T formation in F. novicida during growth in rich medium. We also found that fully virulent F. tularensis produces OMV/T in a similarly regulated manner. Further analysis revealed that OMV/T production is responsive to deprivation of essential amino acids in addition to cysteine, and that the hypo‐vesiculating mutants are defective in responding to this signal. Thus, amino acid starvation, such as encountered by Francisella during host cell invasion, regulates the production of membrane‐derived structures.