Transduction of Virulence within the Species Salmonella typhimurium

Furness, G.; Rowley, D.

doi:10.1099/00221287-15-1-140

Cited by 48 publications

(18 citation statements)

References 8 publications

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“…This study indicates that purine, pyrimidine, histidine, and aromatic amino acid auxotrophs are attenuated for survival within the macrophage in vitro and in the mouse. Purine auxotrophs have been reported as avirulent in S. typhimurium (36), Yersinia pestis (37), and Vibrio cholera (38) as have aroA mutants (11). The avirulence of particular auxotrophs indicates that growth and/or the biosynthesis of virulence factors are required for survival in the macrophage; a mutant requiring metabolites not available in vivo will be unable to metabolize and grow, hence would not survive within the macrophage.…”

Section: Discussionmentioning

confidence: 99%

Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent.

Fields¹,

Swanson²,

Haidaris³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

1,029

798

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Salmonella typhimurium is a facultative intracellular pathogen capable of surviving within phagocytic cells of the reticuloendothelial system. To identify the genes important for intracellular survival, 9516 independent Tn1O insertional mutations were isolated in a virulent strain of S.typhimurium. By using an in vitro assay for survival within macrophages, 83 TnlO mutants have been identified that have a diminished capacity for intracellular survival (designated MS or macrophage survival mutants). All of the MS mutants are less virulent than the parent strain in vivo, demonstrating that, for Salmonella, survival within the macrophage is essential for virulence. Thirty-seven of the MS mutants have been characterized as to their phenotype, including several mutations that confer sensitivity to specific microbiocidal mechanisms of the macrophage.Phagocytic cells are one of the first lines of defense in the body against invading organisms (1); they engulf and kill nonpathogenic and some pathogenic microbes by oxygendependent and -independent mechanisms (2, 3). Intracellular pathogens have evolved means to evade killing by professional phagocytes, thereby allowing them to survive within phagocytic cells (4). Although intracellular pathogens are a clinically important group of microorganisms that cause lingering diseases, such as tuberculosis and typhoid fever, little is known about the molcular mechanisms they employ to interfere with normal phagocyte function.Salmonella typhimurium is a facultative intracellular pathogen of mice (5) 5189The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Section: Discussionmentioning

confidence: 99%

Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent.

Fields¹,

Swanson²,

Haidaris³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

1,029

798

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“…In fact, during the vital step of microbial proliferation in vivo, if certain nutrients are unavailable or withheld within the host, then the capacity of a pathogen to synthesize or acquire these nutrients becomes crucial. Although factors utilized to acquire iron are well accepted as being important for pathogenesis (Litwin and Calderwood, 1993), the importance of acquiring or synthesizing other nutritional factors is less appreciated but supported by a variety of both old (Bacon et al, 1950;Garber et al, 1952;Furness and Rowley, 1956;Levine and Maurer, 1958;Ivanovics et al, 1968;Hatch, 1975;Baselski et al, 1978) and more recent reports (Hosieth and Stocker, 1981;Straley and Harmon, 1984;Austin et al, 1987;Nnalue and Stocker, 1987;O'Callaghan et al, 1988;Bowe et al, 1989;Leung and Finlay, 1991;Mahan et al, 1993;Marquis et al, 1993;McAdam et al, 1995;Ullman and Carter, 1995). Furthermore, the frequent identification of biosynthetic genes as virulence traits in studies that have screened libraries of random gene fusions or randomly generated transposon mutants emphasizes the importance of metabolic genes in microbial pathogenesis (Fields et al, 1986;Leung and Finlay, 1991;Mahan et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…Although nucleotide and amino acid auxotrophy has been shown to attenuate many pathogens, the majority of reports are on intracellular pathogens such as salmonella, listeria, mycobacteria, yersinia, chlamydia and rickettsia (Bacon et al, 1950;Furness and Rowley, 1956; # 1996 Blackwell Science Ltd, Molecular Microbiology, 22, 217-229 Hatch, 1975;Hosieth and Stocker, 1981;Straley and Harmon, 1984;Austin et al, 1987;Nnalue and Stocker, 1987;O'Callaghan et al, 1988;Bowe et al, 1989;Leung and Finlay, 1991;Mahan et al, 1993;Marquis et al, 1993;McAdam et al, 1995;Ullman and Carter, 1995). We are unaware of any such reports involving extraintestinal isolates of E. coli.…”

Section: Discussionmentioning

confidence: 99%

**Identification of two previously unrecognized genes (guaA and argC) important for uropathogenesis**

Russo

Jodush

Brown

et al. 1996

Molecular Microbiology

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Our knowledge of the traits possessed by extraintestinal isolates of Escherichia coli, necessary for growth and survival in urine, is limited. To identify such determinants, transposon (TnphoA'1,4) mutant libraries of a clinical isolate (CP9) were generated and screened for derivatives exhibiting decreased growth in urine in vitro, and for mutants with active lacZ fusions that were induced in urine relative to laboratory medium. Using this approach we identified two genes, guaA (CPA24) and argC (CPI-1), which were previously unrecognized as being important for growth in human urine. Unexpectedly, not only does CPA24 (guaA) not grow in human urine in vitro, but it is sensitive to its effects, undergoing a 2-3 log loss of viability over 6 h. By contrast, CPA24 neither grows nor is killed in M9 minimal medium and artificial urine. Therefore, we postulate that lack of guanine or its derivatives in urine, and the inability of CPA24 to synthesize these compounds de novo, prevents CPA24 from synthesizing other guanine (or derivatives)-dependent products that are critical for growth and survival in urine. Although it seems logical that decreased growth in urine in vitro should correlate with diminished urovirulence, this concept was tested by challenging mice with CPA24 in vivo in a mouse model of urinary tract infection (UTI). Indeed, CPA24 was found to be significantly less virulent compared with its wild-type parent CP9. CPI-1(argC) was identified because of the significant induction of its argC::lacZ fusion in urine. Subsequent testing in urine demonstrated that its growth was significantly diminished in all urine samples tested (four females, three males). Polyamine synthesis is dependent upon, in part, the arginine biosynthetic pathway. Therefore, we tested whether the induction of argC in urine and/or the decreased growth of CPI-1 was a result of low levels of polyamines or arginine in urine. The results suggest that low levels of arginine, but not polyamines, in human urine are responsible. When tested in vivo in the mouse model of UTI, CPI-1 was also found to be significantly less virulent than CP9. In summary, we have established that guaA and argC are the first genes, which we are aware of, that have been shown to contribute to the growth of E. coli in urine in vitro and both have diminished urovirulence in vivo. These results support the concept that urine can be used in vitro as a screening tool to identify urovirulence traits.

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“…De novo purine biosynthesis is essential for infectivity, growth, and virulence of many bacteria in mammals (7,11,17,20,35). Purine biosynthesis is important for extracellular blood-borne pathogens to survive because purine levels in the blood are so low that purine salvage is usually inefficient.…”

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confidence: 99%

Plasmid location of Borrelia purine biosynthesis gene homologs

et al. 1994

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The Lyme disease spirochete Borrelia burgdorferi must survive in both its tick vector and its mammalian host to be maintained in nature. We have identified the B. burgdorferi guaA gene encoding GMP synthetase, an enzyme involved in de novo purine biosynthesis that is important for the survival of bacteria in mammalian blood. This gene encodes a functional product that will complement an Escherichia coli GMP synthetase mutant. The gene is located on a 26-kb circular plasmid, adjacent to and divergent from the gene encoding the outer surface protein C (OspC). The guaB gene homolog encoding IMP dehydrogenase, another enzyme in the purine biosynthetic pathway, is adjacent to guaA. In Borrelia hermsii, a tick-borne relapsing fever spirochete, the guaA and guaB genes are located on a linear plasmid. These are the first genes encoding proteins of known function to be mapped to a borrelial plasmid and the only example of genes encoding enzymes involved in the de novo purine biosynthesis pathway to be mapped to a plasmid in any organism. The unique plasmid location of these and perhaps other housekeeping genes may be a consequence of the segmented genomes in borreliae and reflect the need to adapt to both the arthropod and mammalian environments.

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Transduction of Virulence within the Species Salmonella typhimurium

Cited by 48 publications

References 8 publications

Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent.

Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent.

**Identification of two previously unrecognized genes (guaA and argC) important for uropathogenesis**

Plasmid location of Borrelia purine biosynthesis gene homologs

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