The role of methionine transport-defective mutations in resistance to methionine sulphoximine in Salmonella typhimurium

Betteridge, P. R.; Ayling, P. D.

doi:10.1007/bf00268826

Cited by 23 publications

(12 citation statements)

References 16 publications

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“…Methionine was included in this medium, since bacteria are known to transport MSX by both the glutamate-glutamine and methionine transport systems (4,6,12). The ability to alter the pH of the culture medium was determined by using pH indicator dyes with a narrow pH range in a weakly buffered medium.…”

Section: Methodsmentioning

confidence: 99%

Isolation and characterization of nitrogenase-derepressed mutant strains of cyanobacterium Anabaena variabilis

Spiller¹,

Latorre²,

Hassan³

et al. 1986

J Bacteriol

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A positive selection method for isolation of nitrogenase-derepressed mutant strains of a filamentous cyanobacterium, Anabaena variabilis, is described. Mutant strains that are resistant to a glutamate analog, L-methionine-D,L-sulfoximine, were screened for their ability to produce and excrete NH4' into medium.Mutant strains capable of producing nitrogenase in the presence of NH4' were selected from a population of NH4+-excreting mutants. One of the mutant strains (SA-1) studied in detail was found to be a conditional glutamine auxotroph requiring glutamine for growth in media containing N2, N03 , or low concentrations of NH4' (less than 0.5 mM). This glutamine requirement is a consequence of a block in the assimilation of NH4' produced by an enzyme system like nitrogenase. Glutamate and aspartate failed to substitute for glutamine because of a defect in the transport and utilization of these amino acids. Strain SA-1 assimilated NH4' when the concentration in the medium reached about 0.5 mM, and under these conditions the growth rate was similar to that of the parent. Mutant strain SA-1 produced L-methionine-D,L-sulfoximine-resistant glutamine synthetase activity. Kinetic properties of the enzyme from the parent and mutant were similar. Mutant strain SA-1 can potentially serve as a source of fertilizer nitrogen to support growth of crop plants, since the NH4' produced by nitrogenase, utilizing sunlight and water as sources of energy and reductant, respectively, is excreted into the environment.In free-living, nitrogen-fixing organisms, nitrogenase synthesis and activity are regulated by the presence of NH4' in the medium (3,10,31,45). That NH4+-mediated regulation of nitrogenase synthesis is not exerted by NH4+ itself but is actually a consequence of metabolic products of NH4+ assimilation has been revealed by several lines of evidence.(i) Mutant strains incapable of NH4' assimilation were derepressed for nitrogenase synthesis in the presence of NH4+ (28,31,43,44). (ii) Addition of amino acids to the growth medium repressed nitrogenase synthesis even in nitrogenase-derepressed mutant strains (30). (iii) Inhibition of glutamine synthetase, a primary enzyme responsible for NH4+ assimilation, by a substrate (glutamate) analog, Lmethionine-D,L-sulfoximine (MSX) as well as by other inhibitors led to derepression of nitrogenase synthesis in the presence of NH4+ in all organisms tested (8,13,14,21,31,39). The above described derepression of nitrogenase synthesis is achieved by alteration of cellular physiology leading to a decrease in the rate of glutamate production, since addition of amino acids to the medium reversed the effect (22,29). This set of conditions also derepressed other NH4+-as well as glutamate-producing enzyme systems (NO3 assimilation; histidine and proline utilization) in the cell (16,29).Mutant strains that are blocked at the level of NH4+ assimilation were first described in Klebsiella pneumoniae (32), and such mutant strains not only derepress nitrogenase synthesis but also excrete the NH4+ produce...

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Section: Methodsmentioning

confidence: 99%

Isolation and characterization of nitrogenase-derepressed mutant strains of cyanobacterium Anabaena variabilis

Spiller¹,

Latorre²,

Hassan³

et al. 1986

J Bacteriol

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“…The isolation of metP760 and metP761 (Ayling & Bridgeland, 1972) and metP767 (Betteridge & Ayling, 1975) have already been described. The new metP mutants were isolated in three different ways :…”

Section: Introductionmentioning

confidence: 99%

Methionine Transport in Salmonella typhimurium: Evidence for at Least One Low-affinity Transport System

Ayling¹,

Mojica-A²,

Klopotowski³

1979

Journal of General Microbiology

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The systems which transport methionine in Salmonella typhimurium LT2 have been studied. Fourteen mutants, isolated by three different selection procedures, had similar growth characteristics and defects in the specific transport process showing a Km of 0 . 3 ,~~ for L-methionine, and therefore lack the high-affinity, metP transport system. The sites of mutation in four of the mutants were shown by P1-mediated transduction to be linked (0-3 to 1.1 %) with a proline marker located at unit 7 on the S. typhimurium chromosome. The high-affinity system was subject to both repression and transinhibition by methionine, and it may also be regulated by the metJ and metK genes. There appeared to be at least two additional transport systems with relatively low affinities for methionine in the metP763 mutant strain, with apparent Km values for methionine of 24 ,UM and approximately 1.8 mM. The latter system, with a very low affinity for methionine, was inhibited by leucine. In addition, methionine inhibited leucine transport, suggesting that one of the low-affinity methionine transport systems may actually be a leucine transport system.

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“…Identification of this mutant was not surprising, as the amino acid transporters MetNIQ (methionine permease) and GlnHPQ (glutamine permease) are responsible for transporting MSX in S. enterica. To our knowledge, transport of MSO has not been investigated (55).…”

Section: Figmentioning

confidence: 99%

In Salmonella enterica, the Gcn5-Related Acetyltransferase MddA (Formerly YncA) Acetylates Methionine Sulfoximine and Methionine Sulfone, Blocking Their Toxic Effects

Hentchel¹,

Escalante‐Semerena²

2014

J. Bacteriol.

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Protein and small-molecule acylation reactions are widespread in nature. Many of the enzymes catalyzing acylation reactions belong to the Gcn5-related N-acetyltransferase (GNAT; PF00583) family, named after the yeast Gcn5 protein. The genome of Salmonella enterica serovar Typhimurium LT2 encodes 26 GNATs, 11 of which have no known physiological role. Here, we provide in vivo and in vitro evidence for the role of the MddA (methionine derivative detoxifier; formerly YncA) GNAT in the detoxification of oxidized forms of methionine, including methionine sulfoximine (MSX) and methionine sulfone (MSO). MSX and MSO inhibited the growth of an S. enterica ⌬mddA strain unless glutamine or methionine was present in the medium. We used an in vitro spectrophotometric assay and mass spectrometry to show that MddA acetylated MSX and MSO. An mddA ؉ strain displayed biphasic growth kinetics in the presence of MSX and glutamine. Deletion of two amino acid transporters (GlnHPQ and MetNIQ) in a ⌬mddA strain restored growth in the presence of MSX. Notably, MSO was transported by GlnHPQ but not by MetNIQ. In summary, MddA is the mechanism used by S. enterica to respond to oxidized forms of methionine, which MddA detoxifies by acetyl coenzyme A-dependent acetylation.T he Gcn5-related N-acetyltransferase (GNAT; PF00583) superfamily of proteins (Ͼ10,000 members) is present in all domains of life. GNATs transfer the acetyl group from acetyl coenzyme A (acetyl-CoA) to proteins or small molecules (for reviews, see references 1 and 2). The acetylation targets of GNATs include the N termini of proteins (3, 4), aminoglycoside antibiotics (5), glutamate (6), spermidine (7), aminoalkylphosphonic acid (8), dTDP-fucosamine (9), and tRNAs (10). Some of the first bacterial GNATs characterized were the aminoglycoside N-acetyltransferases from Enterococcus faecium (5) and Serratia marcescens (11), demonstrating GNAT-dependent acetylation and inactivation of antibiotics.GNATs provide protection against a myriad of cellular stressors (5,11,12), and it is possible that the diversity of stressors controlled by GNATs correlates with the environment encountered by the cell. Therefore, the relevance of GNAT function to cell physiology varies among organisms, with respect to not only cellular stressors but metabolic pathways as well. For example, Salmonella enterica (13) and Escherichia coli (14) each contain ϳ26 GNATs, yet actinomycetes, such as Streptomyces lividans (15), encode up to ϳ70 putative GNATs. This suggests that S. lividans occupies a more diverse environment while also maintaining a more complex metabolism.At present, there is limited to no information available on the cellular processes several putative S. enterica GNATs may affect. Not surprisingly, the signals that trigger the synthesis of GNATs, the transcription factors involved in sensing such signals, and the determinants of GNAT substrate specificity remain unknown.In S. enterica, MddA (methionine derivative detoxifier A; formerly YncA [STM1590]) is a putative GNAT with no characterized...

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The role of methionine transport-defective mutations in resistance to methionine sulphoximine in Salmonella typhimurium

Cited by 23 publications

References 16 publications

Isolation and characterization of nitrogenase-derepressed mutant strains of cyanobacterium Anabaena variabilis

Isolation and characterization of nitrogenase-derepressed mutant strains of cyanobacterium Anabaena variabilis

Methionine Transport in Salmonella typhimurium: Evidence for at Least One Low-affinity Transport System

In Salmonella enterica, the Gcn5-Related Acetyltransferase MddA (Formerly YncA) Acetylates Methionine Sulfoximine and Methionine Sulfone, Blocking Their Toxic Effects

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