Lack of nutritional immunity in diabetic skin infections promotes
            <i>Staphylococcus aureus</i>
            virulence

Thurlow, Lance; Stephens, Amelia C.; Hurley, Kelly E.; Richardson, Anthony R.

doi:10.1126/sciadv.abc5569

Cited by 53 publications

(64 citation statements)

References 43 publications

(62 reference statements)

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“…Glucose is an essential nutrient for the human body, serving as a primary fuel for energy production [ 1 ]. Many studies have also suggested that pathogens can exploit glucose as either a nutrient or a signal molecule that induces virulence functions [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Indeed, glucose acquisition is essential for the full virulence potential of pathogenic bacteria [ 11 , 12 ] including Pseudomonas aeruginosa , a major cause of nosocomial infection as well as infection in hosts with compromised defenses [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Glucose-Binding of Periplasmic Protein GltB Activates GtrS-GltR Two-Component System in Pseudomonas aeruginosa

Cao

Lan

2021

Microorganisms

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A two-component system GtrS-GltR is required for glucose transport activity in P. aeruginosa and plays a key role during P. aeruginosa-host interactions. However, the mechanism of action of GtrS-GltR has not been definitively established. Here, we show that gltB, which encodes a periplasmic glucose binding protein, is essential for the glucose-induced activation of GtrS-GltR in P. aeruginosa. We determined that GltB is capable of binding to membrane regulatory proteins including GtrS, the sensor kinase of the GtrS-GltR TCS. We observed that alanine substitution of glucose-binding residues abolishes the ability of GltB to promote the activation of GtrS-GltR. Importantly, like the gtrS deletion mutant, gltB deletion mutant showed attenuated virulence in both Drosophila melanogaster and mouse models of infection. In addition, using CHIP-seq experiments, we showed that the promoter of gltB is the major in vivo target of GltR. Collectively, these data suggest that periplasmic binding protein GltB and GtrS-GltR TCS form a complex regulatory circuit that regulates the virulence of P. aeruginosa in response to glucose.

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Section: Introductionmentioning

confidence: 99%

Glucose-Binding of Periplasmic Protein GltB Activates GtrS-GltR Two-Component System in Pseudomonas aeruginosa

Cao

Lan

2021

Microorganisms

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“…Nevertheless, in our study, the agr system was down-regulated in the S. aureus and C. albicans co-cultured group, while an increase in toxin expression was still observed, which may indicate another pathway managing staphylococcal pathogenicity. A recent study showed that high levels of glycometabolism, leading to increased intracellular ATP, might up-regulate the agr system activity and subsequently promote S. aureus infection [ 40 ]. Interestingly, our transcriptome analysis also revealed an elevation in sugar transmembrane transportation and metabolism, which may explain the increasingly expressed virulence factors ( Figure S6 ).…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus Synergized with Candida albicans to Increase the Pathogenesis and Drug Resistance in Cutaneous Abscess and Peritonitis Murine Models

Niu

et al. 2021

Pathogens

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The mixed species of Staphylococcus aureus and Candida albicans can cause infections on skin, mucosa or bloodstream; however, mechanisms of their cross-kingdom interactions related to pathogenesis and drug resistance are still not clear. Here an increase of S. aureus proliferation and biofilm formation was observed in S. aureus and C. albicans dual-species culture, and the synergistic pathogenic effect was then confirmed in both local (cutaneous abscess) and systemic infection (peritonitis) murine models. According to the transcriptome analysis of the dual-species culture, virulence factors of S. aureus were significantly upregulated. Surprisingly, the beta-lactams and vancomycin-resistant genes in S. aureus as well as azole-resistant genes in C. albicans were also significantly increased. The synergistic effects on drug resistance to both antibacterial and antifungal agents were further proved both in vitro and in cutaneous abscess and peritonitis murine models treated by methicillin, vancomycin and fluconazole. The synergistic interactions between S. aureus and C. albicans on pathogenesis and drug resistance highlight the importance of targeting the microbial interactions in polyspecies-associated infections.

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“…For instance, a recent study interrogating the increased susceptibility of diabetic patients to specific staphylococcal infections highlighted the roles in virulence of S . aureus glucose transporter genes in host nutritional immunity (Thurlow, Stephens, Hurley, & Richardson, 2020). The limitations of some models used in S .…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

IntracellularStaphylococcus aureusand host cell death pathways

Soe

Bedoui

Stinear

et al. 2021

Cellular Microbiology

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Staphylococcus aureus is a major opportunistic human pathogen that is globally prevalent. Although S. aureus and humans may have co‐evolved to the point of commensalism, the bacterium is equipped with virulence factors causing devastating infections. The adoption of an intracellular lifestyle by S. aureus is an important facet of its pathogenesis. Occupying a privileged intracellular compartment permits evasion from the bactericidal actions of host immunity and antibiotics. However, this localization exposes S. aureus to cell‐intrinsic processes comprising autophagy, metabolic challenges and clearance mechanisms orchestrated by host programmed cell death pathways (PCDs), including apoptosis, pyroptosis and necroptosis. Mounting evidence suggests that S. aureus deploys pathoadaptive mechanisms that modulate the expression of its virulence factors to prevent elimination through PCD pathways. In this review, we critically analyse the current literature on the interplay between S. aureus virulence factors with the key, intertwined nodes of PCD. We discuss how S. aureus adaptation to the human host plays an essential role in the evasion of PCD, and we consider future directions to study S. aureus–PCD interactions.

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Lack of nutritional immunity in diabetic skin infections promotes Staphylococcus aureus virulence

Cited by 53 publications

References 43 publications

Glucose-Binding of Periplasmic Protein GltB Activates GtrS-GltR Two-Component System in Pseudomonas aeruginosa

Glucose-Binding of Periplasmic Protein GltB Activates GtrS-GltR Two-Component System in Pseudomonas aeruginosa

Staphylococcus aureus Synergized with Candida albicans to Increase the Pathogenesis and Drug Resistance in Cutaneous Abscess and Peritonitis Murine Models

IntracellularStaphylococcus aureusand host cell death pathways

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