Quantitative analysis of Streptococcus pneumoniae TIGR4 response to in vitro iron restriction by 2‐D LC ESI MS/MS

Nanduri, Bindu; Shah, Pratik; Ramkumar, Mahalingam; Allen, Edward B.; Swiatlo, Edwin; Burgess, Shane C.; Lawrence, Mark L.

doi:10.1002/pmic.200701048

Cited by 27 publications

(25 citation statements)

References 68 publications

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“…Proteomic analyses were carried out with proteins isolated from independent triplicate cultures of wild-type and DpotABCD and speE mutant strains. Proteins were trypsin-digested and desalted as previously described (Nanduri et al, 2008). Briefly, approximately 20 mg protein was reduced with 5 mM dithiothreitol at 65 uC for 5 min and alkylated with 10 mM iodoacetamide at 30 uC for 30 min.…”

Section: Proteomic Analysesmentioning

confidence: 99%

“…For protein identifications where gXcorr50 in a dataset, this method accounts for the discontinuity in identification by including a correction factor. We used a correction factor of 0.5 (Nanduri et al, 2008) for reporting the log 2 ratio of protein abundance.…”

Section: Proteomic Analysesmentioning

confidence: 99%

“…Indeed, pneumococci possess multiple mechanisms for carbohydrate uptake and metabolism that are intricately linked to their pathogenesis (Iyer et al, 2005;Iyer & Camilli, 2007). Transport and biosynthesis of amino acids, manganese and iron have been shown to be important for pneumococcal pathogenesis (Basavanna et al, 2009;Gupta et al, 2009;Nanduri et al, 2008;Rosch et al, 2009;Yesilkaya et al, 2000). A thorough understanding of pneumococcal metabolism is required for designing effective therapeutic and prophylactic strategies.…”

Section: Introductionmentioning

confidence: 99%

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Polyamine biosynthesis and transport mechanisms are crucial for fitness and pathogenesis of Streptococcus pneumoniae

et al. 2011

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Polyamines such as cadaverine, putrescine and spermidine are polycationic molecules that have pleiotropic effects on cells via their interaction with nucleic acids. Streptococcus pneumoniae (the pneumococcus) is a Gram-positive pathogen capable of causing pneumonia, septicaemia, otitis media and meningitis. Pneumococci have a polyamine transport operon (potABCD) responsible for the binding and transport of putrescine and spermidine, and can synthesize cadaverine and spermidine using their lysine decarboxylase (cad) and spermidine synthase (speE) enzymes. Previous studies from our laboratory have shown that an increase in PotD expression is seen following exposure to various stresses, while during infection, potD inactivation significantly attenuates pneumococcal virulence, and anti-PotD immune responses are protective in mice. In spite of their relative importance, not much is known about the global contribution of polyamine biosynthesis and transport pathways to pneumococcal disease. Mutants deficient in polyamine biosynthesis (DspeE or Dcad) or transport genes (DpotABCD) were constructed and were found to be attenuated in murine models of pneumococcal colonization and pneumonia, either alone or in competition with the wild-type strain. The DspeE mutant was also attenuated during invasive disease, while the potABCD and cad genes seemed to be dispensable. HPLC analyses showed reduced intracellular polyamine levels in all mutant strains compared with wild-type bacteria. Highthroughput proteomic analyses indicated reduced expression of growth, replication and virulence factors in mutant strains. Thus, polyamine biosynthesis and transport mechanisms are intricately linked to the fitness, survival and pathogenesis of the pneumococcus in host microenvironments, and may represent important targets for prophylactic and therapeutic interventions.

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Section: Proteomic Analysesmentioning

confidence: 99%

Section: Proteomic Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polyamine biosynthesis and transport mechanisms are crucial for fitness and pathogenesis of Streptococcus pneumoniae

et al. 2011

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“…Because iron-deprivation conditions are directly relevant to the host environment, several recent analyses of transcriptomic and/or proteomic profiles under iron-limiting conditions were performed to identify iron-responsive genes in Staphylococcus aureus [17], Mycobacterium tuberculosis [19], Streptococcus pneumoniae [20], Bacillus anthracis [21], and Listeria monocytogenes [22]. These studies revealed Fur- and/or DtxR-regulated genes as well as iron-responsive genes that may be controlled independently of these known iron-sensing metalloregulators.…”

Section: Iron Metalloregulation: a Pathogen’s Response To Host-inducementioning

confidence: 99%

Metalloregulation of Gram-positive pathogen physiology

Wakeman¹,

Skaar²

2012

Current Opinion in Microbiology

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Due to the unique redox potential of transition metals, many of these elements serve important roles as cofactors in numerous enzymes. However, the reactive nature of metal becomes an intracellular threat when these ions are present in excess. Therefore, all organisms require mechanisms for sensing small fluctuations in metal levels to maintain a controlled balance of uptake, efflux, and sequestration. The ability to sense metal ion concentration is especially important for the survival of pathogenic bacteria because host organisms can both restrict access to essential metals from invading pathogens and utilize the innate toxicity of certain metals for bacterial killing. Host-induced metal ion fluctuations must be rapidly sensed by pathogenic bacteria so that they can activate metal transport systems, alter their physiology to accommodate differences in metal concentrations, and regulate the expression of virulence factors.

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“…Very recently, a combined translatomics/proteomics approach has been applied to 346 identify novel iron-transporting proteins in the pneumococcus (Yang et al 2016). Previously, 347 it had been approached using only proteomics (Nanduri et al 2008;Yang et al 2015). 348…”

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confidence: 99%

Peer Review #1 of "Multi-omic profiling to assess the effect of iron starvation in Streptococcus pneumoniae TIGR4 (v0.2)"

2018

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17We applied multi-omics approaches (transcriptomics, proteomics and metabolomics) to study 18 the effect of iron starvation on the Gram-positive human pathogen Streptococcus pneumoniae 19 to elucidate global changes in the bacterium in a condition similar to what can be found in the 20 host during an infectious episode. We treated the reference strain TIGR4 with the iron 21 chelator deferoxamine mesylate. DNA microarrays revealed changes in the expression of 22 operons involved in multiple biological processes, with a prevalence of genes coding for ion 23 binding proteins. We also studied the changes in protein abundance by 2-DE followed by 24 MALDI-TOF/TOF analysis of total cell extracts and secretome fractions. The main proteomic 25 changes were found in proteins related to the primary and amino sugars metabolism, 26 especially in enzymes with divalent cations as cofactors. Finally, the metabolomic analysis of 27 intracellular metabolites showed altered levels of amino sugars involved in the cell wall 28peptidoglycan metabolism. This work shows the utility of multi-perspective studies that can 29 provide complementary results for the comprehension of how a given condition can influence 30 on global physiological changes in microorganisms. 31 32 3 Introduction 33Bacteria need a plethora of factors for optimal growth, being iron an essential micronutrient. 34Within the human body, the free concentration of this element is approximately 10 -18 M (Yang 35 et al. 2014), which is too low to hold a growth capable of supporting bacterial infections. The 36 low concentrations of free iron within the host are due to the scavenging of this element by 37 different high-affinity proteins (e.g. transferrin, lactoferrin, haemoglobin, etc.) (Froehlich et 38 al. 2009). Therefore, in order to survive in the host, pathogens need to develop especial 39 strategies to uptake the minimum amount that they require of such a nutrient (Nanduri et al. 40 2008), as the direct extraction of this metal cation from host iron-containing proteins or by 41 capturing ferric-binding siderophores from host environments via ABC transporters (Ge & 42 Sun 2014). Moreover, the capacity of bacterial pathogens for iron acquisition represents itself 43 an important virulence determinant (Kanaujia et al. 2015). In addition, pathogens can also 44 modify their energetic metabolism to adapt it to the environmental situation within the host. 45Streptococcus pneumoniae, also known as the pneumococcus, is a Gram-positive 46 microorganism that lives as a commensal in the human respiratory tract and that, under 47 appropriate circumstances, becomes pathogenic, being able to cause high morbidity and 48 mortality (Blasi et al. 2012; Olaya-Abril et al. 2014b). This bacterium is a major cause of 49 mucosal diseases such as otitis media and sinusitis, and is a prevalent pathogen in different 50 invasive diseases including pneumonia, bacteremia, meningitis, and sepsis (O'Brien et al. 512009). Pneumococcal pneumonia, which is the major clinical manife...

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Quantitative analysis of Streptococcus pneumoniae TIGR4 response to in vitro iron restriction by 2‐D LC ESI MS/MS

Cited by 27 publications

References 68 publications

Polyamine biosynthesis and transport mechanisms are crucial for fitness and pathogenesis of Streptococcus pneumoniae

Polyamine biosynthesis and transport mechanisms are crucial for fitness and pathogenesis of Streptococcus pneumoniae

Metalloregulation of Gram-positive pathogen physiology

Peer Review #1 of "Multi-omic profiling to assess the effect of iron starvation in Streptococcus pneumoniae TIGR4 (v0.2)"

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