Reduced Innate Immune Response to a Staphylococcus aureus Small Colony Variant Compared to Its Wild-Type Parent Strain

Ou, Judy; Drilling, Amanda; Cooksley, Clare; Bassiouni, Ahmed; Kidd, Stephen P.; Psaltis, Alkis J.; Wormald, Peter John; Vreugde, Sarah

doi:10.3389/fcimb.2016.00187

Cited by 25 publications

(24 citation statements)

References 44 publications

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“…Here we showed there to be no difference in ability to invade cells between pairs of an isogenic SCV or closely related SCV and an NCP S. epidermidis isolate (see Fig. S2E and F in the supplemental material), as previously shown for S. aureus (65). In addition, we showed a positive correlation between SCV formation and time of intracellular persistence in human fibroblasts with multiple staphylococcal strains and extended these findings to infection in osteoblasts.…”

Section: Discussionsupporting

confidence: 88%

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Survival of Staphylococcus epidermidis in Fibroblasts and Osteoblasts

Perez

Patel

2018

Infect Immun

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is a leading cause of infections associated with indwelling medical devices, including prosthetic joint infection. While biofilm formation is assumed to be the main mechanism underlying the chronic infections causes, we hypothesized that also evades immune killing, contributing to its pathogenesis. Here, we show that prosthetic joint-associated isolates can persist intracellularly within human fibroblasts and inside human and mouse osteoblasts. We also show that the intracellularly persisting bacteria reside primarily within acidic phagolysosomes and that over the course of infection, small colony variants are selected for. Moreover, upon eukaryotic cell death, these bacteria, which can outlive their host, can escape into the extracellular environment, providing them an opportunity to form biofilms on implant surfaces at delayed time points in implant-associated infection. In summary, the acidic phagolysomes of fibroblasts and osteoblasts serve as reservoirs for chronic or delayed infection.

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Section: Discussionsupporting

confidence: 88%

“…( Fig. S2C), suggesting that SCVs do not have an increased ability to invade cells in comparison to NCP isolates, as previously shown for one S. aureus NCP and SCV pair (65).…”

Section: Resultssupporting

confidence: 80%

Survival of Staphylococcus epidermidis in Fibroblasts and Osteoblasts

Perez

Patel

2018

Infect Immun

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“…Pathogens also alter their phenotype to adjust themselves within the epithelium to cause chronic infections. A small colony variant of Staphylococcus aureus often persists intracellularly including in the epithelium due to its ability to exert minimal inflammatory response compared to wild type strains (30). These examples demonstrate a wide array of pathogen mechanisms to outsmart epithelial phagocytosis, which contributes to the disease pathogenesis.…”

Section: How Pathogens Circumvent Phagocytic Abilitymentioning

confidence: 99%

Mechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens

et al. 2020

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Bacterial lung infections are major healthcare challenges killing millions of people worldwide and resulting in a huge economic burden. Both basic and clinical research have elucidated host mechanisms that contribute to the bacterial clearance where an indispensable role of immune cells has been established. However, the role of respiratory epithelial cells in bacterial clearance has garnered limited attention due to their weak inflammatory or phagocytic ability compared to immune cells such as macrophages and neutrophils. These studies often underappreciate the fact that epithelial cells are the most abundant cells in the lung, not only serving as building blocks but also providing immune protection throughout the lung. Epithelial cells function either independently to eradicate the pathogen or communicate with immune cells to orchestrate pathogen clearance. The epithelial cells have multiple mechanisms that include mucus production, antimicrobial peptide production, muco-ciliary clearance, and phagocytosis, all of which contribute to their direct antibacterial function. Secretion of cytokines to recruit immune cells and potentiate their antimicrobial activities is a pathway by which the epithelium contributes to bacterial clearance. Successful pathogens outsmart epithelial resistance and find a way to replicate in sufficient numbers to establish infections in the airway or lung epithelial surfaces. In this mini-review, we discuss evidences that establish important roles for epithelial host defense against invading respiratory bacterial pathogens and demonstrate how pathogens outsmart these epithelial immune mechanisms to successfully establish infection. Finally, we discuss briefly how to boost epithelial immunity to improve outcomes in bacterial lung infections.

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“…For example, the poor drug loading capacity and instability of the liposomes remain important issues. 41 Low loading capacity of polymeric nanoparticles for the polar antimicrobial agents is always faced due to the mutual repulsion between the hydrophilic active molecules and the hydrophobic polymers. The lack of reasonable large-scale production is still another bottleneck for polymeric nanoparticles.…”

Section: Current Challengesmentioning

confidence: 99%

“…39 It was reported that the intracellular infection of WCH-SK2 wild-type promoted the expression of much more factors (TLR2, tissue remodeling factors, and proinflammatory cytokines) than WCH-SK2 SCV (only upregulated expression of TLR2). 40 In addition, the metabolism level and growth of SCVs will be slower than the normal phenotype due to the obstacle of tricarboxylic acid metabolism and energy production, [41][42][43][44] because of dependence to hemin, menadione and thymidine. 1,45…”

mentioning

confidence: 99%

A review on nanosystems as an effective approach against infections of <em>Staphylococcus aureus</em>

Zhou¹,

Li²,

Chen³

et al. 2018

IJN

109

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Staphylococcus aureus (S. aureus) is an important zoonotic bacteria and hazardous for the health of human beings and livestock globally. The characteristics like biofilm forming, facultative intracellular survival, and growing resistance of S. aureus pose a great challenge to its use in therapy. Nanoparticles are considered as a promising way to overcome the infections’ therapeutic problems caused by S. aureus. In this paper, the present progress and challenges of nanoparticles in the treatment of S. aureus infection are focused on stepwise. First, the survival and infection mechanism of S. aureus are analyzed. Second, the treatment challenges posed by S. aureus are provided, which is followed by the third step including the advantages of nanoparticles in improving the penetration and accumulation ability of their payload antibiotics into cell, inhibiting S. aureus biofilm formation, and enhancing the antibacterial activity against resistant isolates. Finally, the challenges and future perspective of nanoparticles for S. aureus infection therapy are introduced. This review will help the readers to realize that the nanosystems can effectively fight against the S. aureus infection by inhibiting biofilm formation, enhancing intracellular delivery, and improving activity against methicillin-resistant S. aureus and small colony variant phenotypes as well as aim to help researchers looking for more efficient nano-systems to combat the S. aureus infections.

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Reduced Innate Immune Response to a Staphylococcus aureus Small Colony Variant Compared to Its Wild-Type Parent Strain

Cited by 25 publications

References 44 publications

Survival of Staphylococcus epidermidis in Fibroblasts and Osteoblasts

Survival of Staphylococcus epidermidis in Fibroblasts and Osteoblasts

Mechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens

A review on nanosystems as an effective approach against infections of <em>Staphylococcus aureus</em>

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