The Host as a Growth Medium*

Garber, E. D.

doi:10.1111/j.1749-6632.1960.tb20108.x

Cited by 57 publications

(23 citation statements)

References 12 publications

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“…While the lack of an elicitor can allow the pathogen access to host plant tissues, there are also positive factors which must come into play in order for pathogenesis to progress. Such factors include production of toxins, extracellular enzymes, and nutrient acquisition systems (Bö lker, 2001;Garber, 1960;Talbot, 2003). Pathogenicity determinants have been traditionally investigated through mutagenesis to a null phenotype which is correlated with non-pathogenicity.…”

Section: Discussionmentioning

confidence: 99%

Siderophore accumulation and phytopathogenicity in Microbotryum violaceum

Birch

Ruddat

2005

Fungal Genetics and Biology

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Section: Discussionmentioning

confidence: 99%

Siderophore accumulation and phytopathogenicity in Microbotryum violaceum

Birch

Ruddat

2005

Fungal Genetics and Biology

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“…Although Garber originally proposed the host as a growth medium over 40 years ago (12), the nutritional environment of most infection sites is poorly defined and often inadequately modeled by laboratory growth media. This lack of knowledge, combined with the limited utility of many animal models, provides significant challenges for mechanistic studies aimed at examining host nutrients as mediators of colonization and disease.…”

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confidence: 99%

Nutritional Cues ControlPseudomonas aeruginosaMulticellular Behavior in Cystic Fibrosis Sputum

2007

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The sputum (mucus) layer of the cystic fibrosis (CF) lung is a complex substrate that provides Pseudomonas aeruginosa with carbon and energy to support high-density growth during chronic colonization. Unfortunately, the CF lung sputum layer has been difficult to mimic in animal models of CF disease, and mechanistic studies of P. aeruginosa physiology during growth in CF sputum are hampered by its complexity. In this study, we performed chromatographic and enzymatic analyses of CF sputum to develop a defined, synthetic CF sputum medium (SCFM) that mimics the nutritional composition of CF sputum. Importantly, P. aeruginosa displays similar phenotypes during growth in CF sputum and in SCFM, including similar growth rates, gene expression profiles, carbon substrate preferences, and cell-cell signaling profiles. Using SCFM, we provide evidence that aromatic amino acids serve as nutritional cues that influence cell-cell signaling and antimicrobial activity of P. aeruginosa during growth in CF sputum.A key concept in bacterial pathogenesis is the ability of invading pathogens to obtain sufficient carbon and energy from the host for in vivo growth. Although Garber originally proposed the host as a growth medium over 40 years ago (12), the nutritional environment of most infection sites is poorly defined and often inadequately modeled by laboratory growth media. This lack of knowledge, combined with the limited utility of many animal models, provides significant challenges for mechanistic studies aimed at examining host nutrients as mediators of colonization and disease. To overcome these challenges, it is critical both to define the nutritional composition of key infection sites and to study bacterial physiology in the context of in vivo-relevant growth substrates.The heritable disease cystic fibrosis (CF) is an archetype for the development of nutritional models with which to study bacterial pathogenesis. A hallmark of CF disease is the accumulation of large volumes of sputum (mucus) within the lungs, which diminishes the host's ability to clear bacterial infections (17,31). The viscous CF lung sputum provides bacteria with a nutritionally rich growth environment composed of host-and bacterial-derived factors (17, 38). The opportunistic pathogen Pseudomonas aeruginosa chronically colonizes the CF lung, where it often grows to high cell densities in CF sputum (Ͼ10 9 cells/ml sputum). Although many other bacterial species persist and grow in the CF lung, chronic P. aeruginosa infection is likely the most clinically relevant, as it is correlated with declining lung function (17). Mechanistically, P. aeruginosa colonization and progression to chronic infection is poorly understood, although potential contributing factors are high-density growth and enhanced fitness of P. aeruginosa in CF sputum. P. aeruginosa fitness has been linked to nutritional components in CF sputum (39), thus necessitating the development of a versatile model that allows examination of CF sputum nutritional cues.The growth environment impacts several...

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“…Although this basic tenet of bacterial pathogenesis, which was espoused originally by Louis Pasteur in the late nineteenth century (21) and more recently by E. D. Garber and other workers (3,6), has been recognized for some time, it has generally been overlooked, and the metabolic pathways critical for proliferation in most infection sites are unknown. Basic knowledge regarding metabolic processes utilized by infecting bacteria is of fundamental importance for understanding bacterial pathogenesis and may offer opportunities for development of novel therapeutics.…”

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confidence: 99%

Characterization of Alanine Catabolism inPseudomonas aeruginosaand Its Importance for Proliferation In Vivo

et al. 2009

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The opportunistic pathogen Pseudomonas aeruginosa causes a variety of infections in immunocompromised individuals, including individuals with the heritable disease cystic fibrosis. Like the carbon sources metabolized by many disease-causing bacteria, the carbon sources metabolized by P. aeruginosa at the host infection site are unknown. We recently reported that L-alanine is a preferred carbon source for P. aeruginosa and that two genes potentially involved in alanine catabolism (dadA and dadX) are induced during in vivo growth in the rat peritoneum and during in vitro growth in sputum (mucus) collected from the lungs of individuals with cystic fibrosis. The goals of this study were to characterize factors required for alanine catabolism in P. aeruginosa and to assess the importance of these factors for in vivo growth. Our results reveal that dadA and dadX are arranged in an operon and are required for catabolism of L-alanine. The dad operon is inducible by L-alanine, D-alanine, and L-valine, and induction is dependent on the transcriptional regulator Lrp. Finally, we show that a mutant unable to catabolize DL-alanine displays decreased competitiveness in a rat lung model of infection.A hallmark of successful bacterial pathogens is their ability to replicate within their hosts, where they not only must acquire nutrients for growth but also often compete with commensal microorganisms. Although this basic tenet of bacterial pathogenesis, which was espoused originally by Louis Pasteur in the late nineteenth century (21) and more recently by E. D. Garber and other workers (3, 6), has been recognized for some time, it has generally been overlooked, and the metabolic pathways critical for proliferation in most infection sites are unknown. Basic knowledge regarding metabolic processes utilized by infecting bacteria is of fundamental importance for understanding bacterial pathogenesis and may offer opportunities for development of novel therapeutics. Indeed, interfering with bacterial metabolism in vivo has been efficacious for inhibiting the pathogenesis of several bacterial pathogens. For example, mutants of the poultry pathogen Campylobacter jejuni that are unable to catabolize L-serine display markedly reduced colonization of the chick gut (32). Likewise, loss of threonine utilization by the pulmonary pathogen Legionella pneumophila prevents replication in alveolar macrophages (26).The gram-negative opportunistic pathogen Pseudomonas aeruginosa is a leading cause of ophthalmic, burn wound, and nosocomial infections and causes chronic pulmonary infections in individuals with cystic fibrosis (CF) (9). In addition, P. aeruginosa colonizes numerous environments outside the host, and its ability to catabolize a wide array of carbon sources likely allows proliferation in these diverse environments. From a host-pathogen perspective, the carbon sources available for growth significantly affect production of extracellular virulence factors and biofilm formation in P. aeruginosa (19,20,29). Despite these findings, we have lit...

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The Host as a Growth Medium*

Cited by 57 publications

References 12 publications

Siderophore accumulation and phytopathogenicity in Microbotryum violaceum

Siderophore accumulation and phytopathogenicity in Microbotryum violaceum

Nutritional Cues ControlPseudomonas aeruginosaMulticellular Behavior in Cystic Fibrosis Sputum

Characterization of Alanine Catabolism inPseudomonas aeruginosaand Its Importance for Proliferation In Vivo

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