Bacteria, iron and pathogenicity

Messenger, Ann J. M.; Barclay, Raymond

doi:10.1016/0307-4412(83)90043-2

Cited by 75 publications

(48 citation statements)

References 27 publications

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“…(ii) The miaB2508::Tn10dCm mutant was grown under conditions in which iron was available (MOPS-glucose minimal medium contains ferrous iron [53]). It has been suggested that this form of iron can be taken up by cells in a passive manner (47). (iii) Limitation of iron in a way which inhibits formation of the ms 2 group leads to reduced growth rates for cells (36).…”

Section: Discussionmentioning

confidence: 99%

The methylthio group (ms2) of N6-(4-hydroxyisopentenyl)-2-methylthioadenosine (ms2io6A) present next to the anticodon contributes to the decoding efficiency of the tRNA

Esberg

Björk

1995

J Bacteriol

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A Salmonella typhimurium LT2 mutant which harbors a mutation (miaB2508::Tn10dCm) that results in a reduction in the activities of the amber suppressors supF30 (tRNA CUA Tyr ), supD10 (tRNA CUA Ser ), and supJ60 (tRNA CUA Leu ) was isolated. The mutant was deficient in the methylthio group (ms A37. The mutation miaB2508::Tn10dCm was 60% linked to the nag gene (min 15) and 40% linked to the fur gene and is located counterclockwise from both of these genes. The growth rates of the mutant in four growth media did not significantly deviate from those of a wild-type strain. The polypeptide chain elongation rate was also unaffected in the mutant. However, the miaB2508::Tn10dCm mutation rendered the cell more resistant or sensitive, compared with a wild-type cell, to several amino acid analogs, suggesting that this mutation influences the regulation of several amino acid biosynthetic operons. The efficiencies of the aforementioned amber suppressors were decreased to as low as 16%, depending on the suppressor and the codon context monitored, demonstrating that the ms 2 group of ms 2 io 6

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Section: Discussionmentioning

confidence: 99%

The methylthio group (ms2) of N6-(4-hydroxyisopentenyl)-2-methylthioadenosine (ms2io6A) present next to the anticodon contributes to the decoding efficiency of the tRNA

Esberg

Björk

1995

J Bacteriol

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“…In bacteria, Fe acts as the cofactor for enzymes involved in energy generation and DNA, amino acid, and vitamin biosynthesis (10,11). Despite being an essential micronutrient, intracellular Fe levels must be tightly controlled to avoid the deleterious effects of hydroxyl radicals that are generated via the Fenton reaction (12).…”

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confidence: 99%

Association of Metal Homeostasis and (p)ppGpp Regulation in the Pathophysiology of Enterococcus faecalis

2017

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In Enterococcus faecalis, the regulatory nucleotides pppGpp and ppGpp, collectively, (p)ppGpp, are required for growth in blood, survival within macrophages, and virulence. However, a clear understanding of how (p)ppGpp promotes virulence in E. faecalis and other bacterial pathogens is still lacking. In the host, the essential transition metals iron (Fe) and manganese (Mn) are not readily available to invading pathogens because of a host-driven process called nutritional immunity. Considering its central role in adaptation to nutritional stresses, we hypothesized that (p)ppGpp mediates E. faecalis virulence through regulation of metal homeostasis. Indeed, supplementation of serum with either Fe or Mn restored growth and survival of the Δrel ΔrelQ [(p)ppGpp 0 ] strain to wild-type levels. Using a chemically defined medium, we found that (p)ppGpp accumulates in response to either Fe depletion or Mn depletion and that the (p)ppGpp 0 strain has a strong growth requirement for Mn that is alleviated by Fe supplementation. Although inactivation of the nutrient-sensing regulator codY restored some phenotypes of the (p)ppGpp 0 strain, transcriptional analysis showed that the (p)ppGpp/CodY network does not promote transcription of known metal transporters. Interestingly, physiologic and enzymatic investigations suggest that the (p)ppGpp 0 strain requires higher levels of Mn in order to cope with high levels of endogenously produced reactive oxygen species (ROS). Because (p)ppGpp mediates antibiotic persistence and virulence in several bacteria, our findings have broad implications and provide new leads for the development of novel therapeutic and preventive strategies against E. faecalis and beyond. KEYWORDS (p)ppGpp, Enterococcus, manganese, metal homeostasis, nutritional immunity, oxidative stress E nterococcus faecalis is a common member of the human gut microbiota but also a leading cause of a number of hospital-acquired infections such as endocarditis and surgical wound and urinary tract infections (1). The association of this opportunistic pathogen with disease relies on its exceptional resilience, which allows it to prevail in the unfavorable hospital setting while providing a competitive advantage over other bacteria during both infection and treatment.Among the most prominent regulators involved in bacterial adaptation to stress are the nucleotide second messengers guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), collectively, (p)ppGpp, best known as the effectors of the stringent response (SR) (2). While initially discovered to accumulate in response to amino acid starvation, (p)ppGpp has also been shown to accumulate in response to restrictions in carbon, fatty acids, and iron, as well as in response to other nonnutritional stresses (3). During the SR, (p)ppGpp accumulation triggers transcriptional alterations that lead to general repression of rapid growth and simultaneous activation of stress survival, nutrient uptake, and biosynthesis pathways. In addition to its involvement in...

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“…Os animais controles não apresentaram nenhuma alteração clínica evidente, mantendo-se aparentemente normais. A resposta clínica ao aporte de ferro no grupo doente justifica-se pela disponibilidade maior de ferro para as atividades metabólicas microbianas, como indicado por Messenger & Barclay (1983).…”

Section: Resultsunclassified

Peroxidação lipídica em cabras com anemia e doença respiratória tratadas com ferro por via parenteral

Santos

Botteon

et al. 2014

Pesq. Vet. Bras.

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RESUMO.-Objetivou-se avaliar a progressão da doença e o dano oxidativo em cabras com anemia e doença respirató-ria mediante aplicação de ferro parenteral. Foram estudadas seis cabras, adultas, com parâmetros eritrocitários indicativos e anemia e manifestações de doença respiratória (tosse, espirros e secreção nasal). O grupo controle foi composto por seis cabras adultas, sadias. As cabras de ambos os grupos após serem submetidos à avaliação clínica receberam dose similar (0,5g) de hidróxido férrico em complexo dextrânico, por via intramuscular. Amostras de sangue colhidas com EDTA, antes da aplicação do ferro e 48 horas depois foram utilizadas para determinação da concentração de substâncias reativas ao ácido tiobarbitúrico (TBARS). Nas cabras doentes antes da aplicação do ferro os valores de TBARS foram equivalentes aos valores mensurados nos controles antes e após a aplicação do ferro (p>0,05). Os valores mensurados nas cabras doentes foram muito mais elevados (p<0,001) no mesmo grupo de animais depois da aplicação do ferro e nos controles antes e após a aplicação. A aplicação do ferro agravou a condição clinica dos animais com doença respiratória, sendo evidenciada uma condição de toxidade refletida pelo estresse oxidativo. Assim sendo, não se deve recomendar tal suplementação nos caprinos acometidos de doenças do aparelho respiratório. Aimed to evaluate the progression of the disease and oxidative damage in goats with anemia and respiratory disease by application of parenteral iron. Six goats, adults, with anemia and respiratory disease (coughing, sneezing and nasal discharge) were studied. The control group was composed of six adults goats, healthy. The goats of both groups after undergoing clinical evaluation received similar dose (0.5g) of ferric hydroxide in complex dextran intramuscularly. Blood samples collected in EDTA before the application of iron and 48 hours were taken for determination of concentration of thiobarbituric acid reactive substances (TBARS). In patients goats before the application of iron TBARS values were equivalent to the measured values in the control group before and after applying the iron (p>0.05). The values measured in patients goats were significantly higher (p<0.001) in the group of animals even after the application of iron and controls before and after application. The application of iron worsened the clinical condition of the animals with respiratory disease, evidencing a condition of toxicity reflected by oxidative stress. Therefore, one should not recommend to supplementation in goats with respiratory diseases.

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Bacteria, iron and pathogenicity

Cited by 75 publications

References 27 publications

The methylthio group (ms2) of N6-(4-hydroxyisopentenyl)-2-methylthioadenosine (ms2io6A) present next to the anticodon contributes to the decoding efficiency of the tRNA

The methylthio group (ms2) of N6-(4-hydroxyisopentenyl)-2-methylthioadenosine (ms2io6A) present next to the anticodon contributes to the decoding efficiency of the tRNA

Association of Metal Homeostasis and (p)ppGpp Regulation in the Pathophysiology of Enterococcus faecalis

Peroxidação lipídica em cabras com anemia e doença respiratória tratadas com ferro por via parenteral

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