Metabolic Cross-talk Between Human Bronchial Epithelial Cells and Internalized Staphylococcus aureus as a Driver for Infection*

Medina, Laura M Palma; Becker, Ann‐Kristin; Michalik, Stephan; Yedavally, Harita; Raineri, Elisa J M; Hildebrandt, Petra; Salazar, Manuela Gesell; Surmann, Kristin; Pförtner, Henrike; Mekonnen, Solomon; Salvati, Anna; Kaderali, Lars; Dijl, Jan Maarten van; Völker, Uwe

doi:10.1074/mcp.ra118.001138

Cited by 33 publications

(48 citation statements)

References 63 publications

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“…Three biological replicates for each condition were analysed. A Q Exactive™ Plus mass spectrometer (Thermo Fisher Scientific, MA, USA) coupled with an UltiMate™ 3000 UHPLC system (Thermo Fisher Scientific, MA, USA) was used for LC‐ESI MS/MS analysis of the tryptic peptide mixtures with the parameters given in Table S4 (Palma Medina et al ., 2019). Data are available at MassiVE (http://ftp://massive.ucsd.edu/MSV000084766/).…”

Section: Methodsmentioning

confidence: 99%

Impact of high salinity and the compatible solute glycine betaine on gene expression of Bacillus subtilis

Rath

Sappa

Hoffmann

et al. 2020

Environmental Microbiology

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Summary The Gram‐positive bacterium Bacillus subtilis is frequently exposed to hyperosmotic conditions. In addition to the induction of genes involved in the accumulation of compatible solutes, high salinity exerts widespread effects on B. subtilis physiology, including changes in cell wall metabolism, induction of an iron limitation response, reduced motility and suppression of sporulation. We performed a combined whole‐transcriptome and proteome analysis of B. subtilis 168 cells continuously cultivated at low or high (1.2 M NaCl) salinity. Our study revealed significant changes in the expression of more than one‐fourth of the protein‐coding genes and of numerous non‐coding RNAs. New aspects in understanding the impact of high salinity on B. subtilis include a sustained low‐level induction of the SigB‐dependent general stress response and strong repression of biofilm formation under high‐salinity conditions. The accumulation of compatible solutes such as glycine betaine aids the cells to cope with water stress by maintaining physiologically adequate levels of turgor and also affects multiple cellular processes through interactions with cellular components. Therefore, we additionally analysed the global effects of glycine betaine on the transcriptome and proteome of B. subtilis and revealed that it influences gene expression not only under high‐salinity, but also under standard growth conditions.

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Section: Methodsmentioning

confidence: 99%

Impact of high salinity and the compatible solute glycine betaine on gene expression of Bacillus subtilis

Rath

Sappa

Hoffmann

et al. 2020

Environmental Microbiology

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“…While S. aureus infecting the airway are adapting to the local environment, a similar process of metabolic adaptation occurs in host cells. In response to internalized staphylococci, human bronchial epithelial cells increase glucose uptake and catabolism, as well as amino acid utilization (108). These metabolic changes observed in bronchial epithelial cells upon S. aureus infection are reminiscent of other studies using HeLa cells and more physiologically relevant cell types, such as bone marrow-derived macrophages (BMDMs) (111) and human primary keratinocytes (112).…”

Section: Metabolic Competition Between Host and S Aureusmentioning

confidence: 74%

“…changes include increased levels of phosphoenolpyruvate (PEP) carboxykinase (PckA) involved in gluconeogenesis (108). Of note, the upregulation of these enzymes was previously shown to be important particularly in glutamate catabolism to supply intermediates such as oxaloacetate, α-ketoglutarate and succinyl-coenzyme-A and subsequently gluconeogenesis via PckA when glucose is depleted (Figure 2A) (109).…”

Section: Metabolic Adaptation Of S Aureus To the Lungmentioning

confidence: 99%

“…Following invasion of human bronchial epithelial cells, S. aureus adapt to the intracellular environment. Internalized bacteria display population heterogeneity with one bacterial subset replicating and eventually causing host cell death whilst another subset persists by reducing growth rates (Figure 2A) (108). In order to survive and persist, the latter subset increases fermentation and amino acid catabolism, upregulating enzymes including 2-oxoglutarate dehydrogenase (SucA), succinyl coenzyme-A synthetase (SucC), succinate dehydrogenase (SdhA), and fumarase/fumarate hydratase (FumC), which are involved in the TCA cycle activity (Figure 2A, red arrows).…”

Section: Metabolic Adaptation Of S Aureus To the Lungmentioning

confidence: 99%

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Pulmonary Pathogens Adapt to Immune Signaling Metabolites in the Airway

Riquelme

Lung

2020

Front. Immunol.

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A limited number of pulmonary pathogens are able to evade normal mucosal defenses to establish acute infection and then adapt to cause chronic pneumonias. Pathogens, such as Pseudomonas aeruginosa or Staphylococcus aureus, are typically associated with infection in patients with underlying pulmonary disease or damage, such as cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). To establish infection, bacteria express a well-defined set of so-called virulence factors that facilitate colonization and activate an immune response, gene products that have been identified in murine models. Less well-understood are the adaptive changes that occur over time in vivo, enabling the organisms to evade innate and adaptive immune clearance mechanisms. These colonizers proliferate, generating a population sufficient to provide selection for mutants, such as small colony variants and mucoid variants, that are optimized for long term infection. Such host-adapted strains have evolved in response to selective pressure such as antibiotics and the recruitment of phagocytes at sites of infection and their release of signaling metabolites (e.g., succinate). These metabolites can potentially function as substrates for bacterial growth and but also generate oxidant stress. Whole genome sequencing and quantified expression of selected genes have helped to explain how P. aeruginosa and S. aureus adapt to the presence of these metabolites over the course of in vivo infection. The serial isolation of clonally related strains from patients with cystic fibrosis has provided the opportunity to identify bacterial metabolic pathways that are altered under this immune pressure, such as the anti-oxidant glyoxylate and pentose phosphate pathways, routes contributing to the generation of biofilms. These metabolic pathways and biofilm itself enable the organisms to dissipate oxidant stress, while providing protection from phagocytosis. Stimulation of host immune signaling metabolites by these pathogens drives bacterial adaptation and promotes their persistence in the airways. The inherent metabolic flexibility of P. aeruginosa and S. aureus is a major factor in their success as pulmonary pathogens.

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“…In order to decrease the urea concentration for efficient trypsin digestion, 60 µL aqueous ammonium bicarbonate solution (20 mmol L –1 ; ABC‐buffer) were added. S. aureus proteins were extracted with lysostaphin and digested with trypsin as described before . S. suis on filters were incubated for 30 min, at 37 °C, 1400 rpm (Eppendorf ThermoMixer, Germany) with 30 µL ABC‐buffer (50 mmol L –1 ) containing 2.5 ng lysozyme to disrupt the cells.…”

mentioning

confidence: 99%

Improving Proteome Coverage for Small Sample Amounts: An Advanced Method for Proteomics Approaches with Low Bacterial Cell Numbers

et al. 2019

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Proteome analyses are often hampered by the low amount of available starting material like a low bacterial cell number obtained from in vivo settings. Here, the single pot solid‐phase enhanced sample preparation (SP3) protocol is adapted and combined with effective cell disruption using detergents for the proteome analysis of bacteria available in limited numbers only. Using this optimized protocol, identification of peptides and proteins for different Gram‐positive and Gram‐negative species can be dramatically increased and, reliable quantification can also be ensured. This adapted method is compared to already established strain‐specific sample processing protocols for Staphylococcus aureus, Streptococcus suis, and Legionella pneumophila. The highest species‐specific increase in identifications is observed using the adapted method with L. pneumophila samples by increasing protein and peptide identifications up to 300% and 620%, respectively. This increase is accompanied by an improvement in reproducibility of protein quantification and data completeness between replicates. Thus, this protocol is of interest for performing comprehensive proteomics analyses of low bacterial cell numbers from different settings ranging from infection assays to environmental samples.

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Metabolic Cross-talk Between Human Bronchial Epithelial Cells and Internalized Staphylococcus aureus as a Driver for Infection*

Abstract: U. (2019). Metabolic cross-talk between human bronchial epithelial cells and internalized Staphylococcus aureus as a driver for infection.

Cited by 33 publications

References 63 publications

Impact of high salinity and the compatible solute glycine betaine on gene expression of Bacillus subtilis

Impact of high salinity and the compatible solute glycine betaine on gene expression of Bacillus subtilis

Pulmonary Pathogens Adapt to Immune Signaling Metabolites in the Airway

Improving Proteome Coverage for Small Sample Amounts: An Advanced Method for Proteomics Approaches with Low Bacterial Cell Numbers

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