Staphylococcus aureus Survives in Cystic Fibrosis Macrophages, Forming a Reservoir for Chronic Pneumonia

Cao, Li; Wu, Yuqing; Riehle, Andrea; Ma, Jie; Kamler, Markus; Gulbins, Erich; Grassmé, Heike

doi:10.1128/iai.00883-16

Cited by 37 publications

(40 citation statements)

References 47 publications

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“…In vitro and animal model studies suggest that those with CF exhibit dysregulated inflammatory responses to S. aureus [ 13 ] and the organism may even survive within macrophages [ 14 ]. S. aureus is equally implicated in early lung damage in such studies [ 15 ] and detection is independently associated with lower respiratory tract inflammation [ 16 ].…”

Section: Microbiologymentioning

confidence: 99%

Staphylococcus aureus in cystic fibrosis: problem bug or an innocent bystander?

Hurley¹

2018

Breathe

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Staphylococcus aureus is a commonly encountered organism in day-to-day living. However, the epidemiology is complicated by three different patterns of carriage. Up to 60% of the population hosts the organism at any one time and, while ∼20% are considered “persistent carriers” due to their status of being continuous hosts of the same strain, a further 20% never host S. aureus and so are considered non-carriers [1]. S. aureus is commonly encountered in childhood with nasopharyngeal carriage among healthy children as high as 48% in the USA [2] and 36% in the Netherlands [3]. S. aureus carriage varies markedly by occupation, as do the proportions of those who carry antibiotic resistant strains (methicillin-resistant S. aureus (MRSA)) [1].

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Section: Microbiologymentioning

confidence: 99%

Staphylococcus aureus in cystic fibrosis: problem bug or an innocent bystander?

Hurley¹

2018

Breathe

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“…Several studies demonstrate the existence of intracellular S. aureus in tissue and phagocytic cells in vivo [e.g. 12, 13-16]. Invasion of tissue cells is facilitated by numerous different bacterial adhesins and followed by escape from the bacteria-containing vacuole and cytosolic replication [reviewed in 17, 18, 19].…”

Section: Introductionmentioning

confidence: 99%

IntracellularStaphylococcus aureusemploys the cysteine protease staphopain A to induce host cell death in epithelial cells

Stelzner

Hertlein

Sroka

et al. 2020

Preprint

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Staphylococcus aureus is a major human pathogen, which can invade and survive in non-professional and professional phagocytes. Intracellularity is thought to contribute to pathogenicity and persistence of the bacterium. Upon internalization by epithelial cells, cytotoxic S. aureus strains can escape from the phagosome, replicate in the cytosol and induce host cell death. Here, we identified a staphylococcal cysteine protease to induce cell death by intracellular S. aureus after translocation into the host cell cytoplasm. We demonstrated that loss of staphopain A function leads to delayed onset of host cell death and prolonged intracellular replication of S. aureus in epithelial cells. Overexpression of staphopain A in a non-cytotoxic strain facilitated intracellular killing of the host cell even in the absence of detectable intracellular replication. Moreover, staphopain A contributed to efficient colonization of the lung in a mouse pneumonia model. Our study suggests that staphopain A is utilized by S. aureus to mediate escape from the host cell and thus contributes to tissue destruction and dissemination of infection. Author Summary Staphylococcus aureus is a well-known antibiotic-resistant pathogen that emerges in hospital and community settings and can cause a variety of diseases ranging from skin abscesses to lung inflammation and blood poisoning. The bacterium asymptomatically colonizes the upper respiratory tract and skin of about one third of the human population and takes advantage of opportune conditions, like immunodeficiency or breached barriers, to cause infection. Although S. aureus is not regarded as a professional intracellular bacterium, it can be internalized by human cells and subsequently exit the host cells by induction of cell death, which is considered to cause tissue destruction and spread of infection. The bacterial virulence factors and underlying molecular mechanisms involved in the intracellular lifestyle of S. aureus remain largely unknown. We identified a bacterial cysteine protease to contribute to host cell death mediated by intracellular S. aureus. Staphopain A induced killing of the host cell after translocation of the pathogen into the cell cytosol, while bacterial proliferation was not required. Further, the protease enhanced survival of the pathogen during lung infection. These findings reveal a novel, intracellular role for the bacterial protease staphopain A.

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“…treatment, S. aureus is able to persist over several years (Kahl et al, 1998;Schwerdt et al, 2018), causing inflammation (Sagel et al, 2009) and a decline in lung function (Junge et al, 2016). The long-term persistence of S. aureus might be facilitated by its ability to enter, replicate, and reside in professional phagocytes like macrophages (Li et al, 2017) and neutrophils (Gresham et al, 2000) and non-professional phagocytes as keratinocytes, fibroblasts, endothelial, and epithelial cells (Strobel et al, 2016), including also CF cells (Jarry & Cheung, 2006;Kahl et al, 2000). Furthermore, in some S. aureus CF isolates long-term persistence might be caused by enhanced production of nuclease, which was shown to facilitate bacterial escape from neutrophil extracellular traps (Herzog et al, 2019).…”

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confidence: 99%

Importance of superoxide dismutases A and M for protection ofStaphylococcus aureusin the oxidative stressful environment of cystic fibrosis airways

Janina

Chaves‐Moreno

Niemann

et al. 2020

Cellular Microbiology

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Staphylococcus aureus is one of the earliest pathogens that persists the airways of cystic fibrosis (CF) patients and contributes to increased inflammation and decreased lung function. In contrast to other staphylococci, S. aureus possesses two superoxide dismutases (SODs), SodA and SodM, with SodM being unique to S. aureus. Both SODs arm S. aureus for its fight against oxidative stress, a by‐product of inflammatory reactions. Despite complex investigations, it is still unclear if both enzymes are crucial for the special pathogenicity of S. aureus. To investigate the role of both SODs during staphylococcal persistence in CF airways, we analysed survival and gene expression of S. aureus CF isolates and laboratory strains in different CF‐related in vitro and ex vivo settings. Bacteria located in inflammatory and oxidised CF sputum transcribed high levels of sodA and sodM. Especially expression values of sodM were remarkably higher in CF sputum than in bacterial in vitro cultures. Interestingly, also S. aureus located in airway epithelial cells expressed elevated transcript numbers of both SODs, indicating that S. aureus is exposed to oxidative stress at various sites within CF airways. Both enzymes promoted survival of S. aureus during polymorphonuclear leukocyte killing and seem to act compensatory, thereby giving evidence that the interwoven interaction of SodA and SodM contributes to S. aureus virulence and facilitates S. aureus persistence within CF airways.

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Staphylococcus aureus Survives in Cystic Fibrosis Macrophages, Forming a Reservoir for Chronic Pneumonia

Cited by 37 publications

References 47 publications

Staphylococcus aureus in cystic fibrosis: problem bug or an innocent bystander?

Staphylococcus aureus in cystic fibrosis: problem bug or an innocent bystander?

IntracellularStaphylococcus aureusemploys the cysteine protease staphopain A to induce host cell death in epithelial cells

Importance of superoxide dismutases A and M for protection ofStaphylococcus aureusin the oxidative stressful environment of cystic fibrosis airways

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