Who’s in control? Regulation of metabolism and pathogenesis in space and time

King, Alyssa N.; Mets, François De; Brinsmade, Shaun R.

doi:10.1016/j.mib.2020.05.009

Cited by 20 publications

(17 citation statements)

References 77 publications

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“…The rCCR phenotypes were not consistent with the commonly applied, systems biology criterion, which maximizes growth rate 43 , 44 . Pseudomonads are commonly found in consortia and the rCCR metabolism is proposed to provide fitness advantages in these competitive environments 59 , 60 . Consortia with populations expressing rCCR and cCCR phenotypes have the metabolic basis for an effective division of labor, thus avoiding overlapping substrate preferences which can result in species competition and exclusion 61 – 65 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa reverse diauxie is a multidimensional, optimized, resource utilization strategy

McGill

Yung

Hunt

et al. 2021

Sci Rep

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Pseudomonas aeruginosa is a globally-distributed bacterium often found in medical infections. The opportunistic pathogen uses a different, carbon catabolite repression (CCR) strategy than many, model microorganisms. It does not utilize a classic diauxie phenotype, nor does it follow common systems biology assumptions including preferential consumption of glucose with an ‘overflow’ metabolism. Despite these contradictions, P. aeruginosa is competitive in many, disparate environments underscoring knowledge gaps in microbial ecology and systems biology. Physiological, omics, and in silico analyses were used to quantify the P. aeruginosa CCR strategy known as ‘reverse diauxie’. An ecological basis of reverse diauxie was identified using a genome-scale, metabolic model interrogated with in vitro omics data. Reverse diauxie preference for lower energy, nonfermentable carbon sources, such as acetate or succinate over glucose, was predicted using a multidimensional strategy which minimized resource investment into central metabolism while completely oxidizing substrates. Application of a common, in silico optimization criterion, which maximizes growth rate, did not predict the reverse diauxie phenotypes. This study quantifies P. aeruginosa metabolic strategies foundational to its wide distribution and virulence including its potentially, mutualistic interactions with microorganisms found commonly in the environment and in medical infections.

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Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa reverse diauxie is a multidimensional, optimized, resource utilization strategy

McGill

Yung

Hunt

et al. 2021

Sci Rep

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“…M. tuberculosis encodes for several two-component systems that allow the pathogen to respond to environmental cues, including oxygen. Two-component systems are composed of a sensor kinase and a cognate response regulator (reviewed: [126][127][128]). Recently, it was reported that an M. tuberculosis strain lacking the M. tuberculosis two-component regulatory system MtrA/MtrB (MtrAB) showed a decreased viability under hypoxia.…”

Section: Bacterial Oxygen Sensingmentioning

confidence: 99%

Mechanisms controlling bacterial infection in myeloid cells under hypoxic conditions

Hayek

Schatz

Bogdan

et al. 2020

Cell. Mol. Life Sci.

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Various factors of the tissue microenvironment such as the oxygen concentration influence the host–pathogen interaction. During the past decade, hypoxia-driven signaling via hypoxia-inducible factors (HIF) has emerged as an important factor that affects both the pathogen and the host. In this chapter, we will review the current knowledge of this complex interplay, with a particular emphasis given to the impact of hypoxia and HIF on the inflammatory and antimicrobial activity of myeloid cells, the bacterial responses to hypoxia and the containment of bacterial infections under oxygen-limited conditions. We will also summarize how low oxygen concentrations influence the metabolism of neutrophils, macrophages and dendritic cells. Finally, we will discuss the consequences of hypoxia and HIFα activation for the invading pathogen, with a focus on Pseudomonas aeruginosa, Mycobacterium tuberculosis, Coxiella burnetii, Salmonella enterica and Staphylococcus aureus. This includes a description of the mechanisms and microbial factors, which the pathogens use to sense and react to hypoxic conditions.

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“…Specific examples of sRNAs targeting TCS genes are presented in Table 2. Such regulatory connections have recently been described in both Gram-negative and Gram-positive pathogens and are associated with stress response, colony morphology, motility, competence control, and other virulence-related processes [13,192]. The advantages of combining sRNA-mediated regulation with protein-mediated control are multiple.…”

Section: Participation Of Srnas In Regulatory Networkmentioning

confidence: 99%

Interplay between Regulatory RNAs and Signal Transduction Systems during Bacterial Infection

Piattelli

Peltier

Soutourina

2020

Genes

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The ability of pathogenic bacteria to stably infect the host depends on their capacity to respond and adapt to the host environment and on the efficiency of their defensive mechanisms. Bacterial envelope provides a physical barrier protecting against environmental threats. It also constitutes an important sensory interface where numerous sensing systems are located. Signal transduction systems include Two-Component Systems (TCSs) and alternative sigma factors. These systems are able to sense and respond to the ever-changing environment inside the host, altering the bacterial transcriptome to mitigate the impact of the stress. The regulatory networks associated with signal transduction systems comprise small regulatory RNAs (sRNAs) that can be directly involved in the expression of virulence factors. The aim of this review is to describe the importance of TCS- and alternative sigma factor-associated sRNAs in human pathogens during infection. The currently available genome-wide approaches for studies of TCS-regulated sRNAs will be discussed. The differences in the signal transduction mediated by TCSs between bacteria and higher eukaryotes and the specificity of regulatory RNAs for their targets make them appealing targets for discovery of new strategies to fight against multi-resistant bacteria.

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Who’s in control? Regulation of metabolism and pathogenesis in space and time

Cited by 20 publications

References 77 publications

Pseudomonas aeruginosa reverse diauxie is a multidimensional, optimized, resource utilization strategy

Pseudomonas aeruginosa reverse diauxie is a multidimensional, optimized, resource utilization strategy

Mechanisms controlling bacterial infection in myeloid cells under hypoxic conditions

Interplay between Regulatory RNAs and Signal Transduction Systems during Bacterial Infection

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