Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species

Gibson, Josie; Pidwill, Grace R.; Carnell, Oliver; Surewaard, Bas G. J.; Shamarina, Daria; Sutton, Joshua A. F.; Jeffery, Charlotte; Derré-Bobillot, Aurélie; Archambaud, Cristel; Siggins, Matthew K.; Pollitt, Eric J. G.; Johnston, Simon A.; Serror, Pascale; Sriskandan, Shiranee; Renshaw, Stephen A.; Foster, Simon J.

doi:10.1371/journal.ppat.1009880

Cited by 12 publications

(16 citation statements)

References 59 publications

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“…We have previously established a macrophage infection assay, using both cultured RAW264.7 cells and human monocyte derived macrophages (MDMs), which leads to the formation of bacterial masses 17 , as depicted in Fig. 1 a.…”

Section: Resultsmentioning

confidence: 99%

“…A key facet of the macrophage arsenal employed to combat S. aureus are reactive oxygen species (ROS). ROS are pivotal in a phenomenon termed “augmentation” where the presence of commensal organisms, or their components, within the S. aureus inoculum ameliorates ROS within macrophages leading to increased bacterial survival 17 . This is important as S. aureus will generally infect the host by emerging from the current microflora of the host environment.…”

Section: Introductionmentioning

confidence: 99%

“…This has firmly established the phenomenon as a key, early aspect of disease and that macrophages are involved. However, to dissect the relationship between S. aureus and macrophages, here we have utilised an in vitro macrophage model of S. aureus interaction, using an experimental and modelling approach 17 . We show that clonality is host-dependent, as increasing the multiplicity of infection (MOI) did not enhance numbers of bacterial masses formed.…”

Section: Introductionmentioning

confidence: 99%

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Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches

Pidwill

Pyrah

Sutton

et al. 2023

Sci Rep

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Staphylococcus aureus is a human commensal and also an opportunist pathogen causing life threatening infections. During S. aureus disease, the abscesses that characterise infection can be clonal, whereby a large bacterial population is founded by a single or few organisms. Our previous work has shown that macrophages are responsible for restricting bacterial growth such that a population bottleneck occurs and clonality can emerge. A subset of phagocytes fail to control S. aureus resulting in bacterial division, escape and founding of microabscesses that can seed other host niches. Here we investigate the basis for clonal microabscess formation, using in vitro and in silico models of S. aureus macrophage infection. Macrophages that fail to control S. aureus are characterised by formation of intracellular bacterial masses, followed by cell lysis. High-resolution microscopy reveals that most macrophages had internalised only a single S. aureus, providing a conceptual framework for clonal microabscess generation, which was supported by a stochastic individual-based, mathematical model. Once a threshold of masses was reached, increasing the number of infecting bacteria did not result in greater mass numbers, despite enhanced phagocytosis. This suggests a finite number of permissive, phagocyte niches determined by macrophage associated factors. Increased understanding of the parameters of infection dynamics provides avenues for development of rational control measures.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches

Pidwill

Pyrah

Sutton

et al. 2023

Sci Rep

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“…The commensal bacteria found in the anterior naris are S. epidermidis , Cutibacterium acnes , Dolosigranulum pigrum , Finegoldia magna , Corynebacterium spp., Moraxella spp., Peptoniphilus spp., and Anaerococcus spp ( Kumpitsch et al., 2019 ).. S. epidermidis that was used in the current study is one of the most predominant opportunistic bacterial species in the naris, suggesting the great possibility of coexistence of both bacteria species in the same location. Importantly, it has been shown that a broad range of microorganisms including Micrococcus luteus , Escherichia Coli , Roseomonas mucosa , and Saccharomyces cerevisiae are able to augment the S. aureus pathogenicity in sepsis ( Boldock et al., 2018 ; Gibson et al., 2021 ). Indeed, a study of the overall microbial composition in anterior nare bacterial community in 40 healthy individuals revealed that in most of the cases the other commensal strains were much more prevalent in high abundance than S. aureus ( Wos-Oxley et al., 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Commensal Bacteria Augment Staphylococcus aureus septic Arthritis in a Dose-Dependent Manner

Ali

Mohammad

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundSeptic arthritis is considered one of the most dangerous joints diseases and is mainly caused by the Gram-positive bacterium Staphylococcus aureus (S. aureus). Human skin commensals are known to augment S. aureus infections. The aim of this study was to investigate if human commensals could augment S. aureus-induced septic arthritis.MethodNMRI mice were inoculated with S. aureus alone or with a mixture of S. aureus together with either of the human commensal Staphylococcus epidermidis (S. epidermidis) or Streptococcus mitis (S. mitis). The clinical, radiological and histopathological changes due to septic arthritis were observed. Furthermore, the serum levels of chemokines and cytokines were assessed.ResultsMice inoculated with a mixture of S. aureus and S. epidermidis or S. mitis developed more severe and frequent clinical arthritis compared to mice inoculated with S. aureus alone. This finding was verified pathologically and radiologically. Furthermore, the ability of mice to clear invading bacteria in the joints but not in kidneys was hampered by the bacterial mixture compared to S. aureus alone. Serum levels of monocyte chemoattractant protein 1 were elevated at the early phase of disease in the mice infected with bacterial mixture compared with ones infected with S. aureus alone. Finally, the augmentation effect in septic arthritis development by S. epidermidis was bacterial dose-dependent.ConclusionThe commensal bacteria dose-dependently augment S. aureus-induced septic arthritis in a mouse model of septic arthritis.

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“…Co-infection of S. aureus and commensal bacteria only led to the proliferation of S. aureus within KCs [ 80 ]. The commensal bacteria augment S. aureus infection by acting as a sink for ROS production, thereby increasing the chance that S. aureus can initiate replication inside KCs [ 81 ]. Many other bacterial, fungal, or parasitic species have been shown to use circulating phagocytes as an opportunity for dissemination, such as Mycobacterium tuberculosis , Listeria monocytogenes , Leishmania , and Cryptococcus neoformans [ 82 , 83 , 84 , 85 ].…”

Section: Bacterial Specificity Of the Intracellular Reservoirmentioning

confidence: 99%

Intracellular Habitation of Staphylococcus aureus: Molecular Mechanisms and Prospects for Antimicrobial Therapy

Hommes

Surewaard

2022

Biomedicines

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Methicillin-resistant Staphylococcus aureus (MRSA) infections pose a global health threat, especially with the continuous development of antibiotic resistance. As an opportunistic pathogen, MRSA infections have a high mortality rate worldwide. Although classically described as an extracellular pathogen, many studies have shown over the past decades that MRSA also has an intracellular aspect to its infectious cycle, which has been observed in vitro in both non-professional as well as professional phagocytes. In vivo, MRSA has been shown to establish an intracellular niche in liver Kupffer cells upon bloodstream infection. The staphylococci have evolved various evasion strategies to survive the antimicrobial environment of phagolysosomes and use these compartments to hide from immune cells and antibiotics. Ultimately, the host cells get overwhelmed by replicating bacteria, leading to cell lysis and bacterial dissemination. In this review, we describe the different intracellular aspects of MRSA infection and briefly mention S. aureus evasion strategies. We discuss how this intracellular niche of bacteria may assist in antibiotic tolerance development, and lastly, we describe various new antibacterial strategies that target the intracellular bacterial niche.

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Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species

Cited by 12 publications

References 59 publications

Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches

Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches

Commensal Bacteria Augment Staphylococcus aureus septic Arthritis in a Dose-Dependent Manner

Intracellular Habitation of Staphylococcus aureus: Molecular Mechanisms and Prospects for Antimicrobial Therapy

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