Inside job: Staphylococcus aureus host-pathogen interactions

Horn, Jessica; Stelzner, Kathrin; Rudel, Thomas; Fraunholz, Martin

doi:10.1016/j.ijmm.2017.11.009

Cited by 170 publications

(172 citation statements)

References 264 publications

Supporting

Mentioning

168

Contrasting

Order By: Relevance

“…Escape from the phagosome is followed by intracellular replication of S. aureus in the host cell cytoplasm of non-phagocytic cells (S3C and D Fig, S1 movie) [18, 66]. Using live cell imaging we monitored replication of JE2 in HeLa cells, which was accompanied by contraction and rounding of the host cell (Fig 3C, upper panel, S2 movie).…”

Section: Resultsmentioning

confidence: 99%

“…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]. In professional phagocytes, intracellular S. aureus is able to resist the antimicrobial attack by the host cell and replication occurs within phagosomes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Stelzner

Hertlein

Sroka

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…S. aureus possesses several virulence mechanisms to accommodate a diversity of niches. For example, S. aureus can invade and survive in host cells including epithelial cells, osteoblasts, neutrophils, and macrophages resulting in chronic infections . Indeed, several main antibiotics such as β‐lactams lack efficacy to eradicate intracellular pathogens, as they can poorly bypass cell membranes and/or are rapidly cleared off by efflux pumps ( Figure a).…”

Section: Resultsmentioning

confidence: 99%

Compartmentalized Encapsulation of Two Antibiotics in Porous Nanoparticles: an Efficient Strategy to Treat Intracellular Infections

Semiramoth

Hall

et al. 2019

Part & Part Syst Charact

View full text Add to dashboard Cite

Combinatorial drug therapies emerge among the most promising strategies to treat complex pathologies such as cancer and severe infections. Biocompatible nanoparticles of mesoporous iron carboxylate metal–organic framework (nanoMOFs) are used here to address the challenging aspects related to the coincorporation of two antibiotics. Amoxicillin and potassium clavulanate, a typical example of drugs used in tandem, are efficiently coincorporated with payloads up to 36 wt%. Due to the occurrence of two distinct pore sizes/apertures within the MOF architecture, each drug is able to infiltrate the porous framework and localize within separate compartments. Molecular simulations predict drug loadings and locations consistent with experimental findings. Drug loaded nanoMOFs that are internalized by Staphylococcus aureus infected macrophages are able to colocalize with the pathogen, which in turn leads to an alleviation of bacterial infection. The data also reveal potential antibacterial properties of nanoMOFs alone as well as their ability to deliver a high payload of drugs to fight intracellular bacteria. These results pave the way toward the design of engineered “all‐in‐one” nanocarriers in which both the loaded drugs and their carrier play a role in fighting intracellular infections.

show abstract

“…Staphylococcus aureus invades a variety of non‐professional phagocytic cells (NPPC): epithelial and endothelial cells, osteoblasts, fibroblast, keratinocytes, and others (see, for instance, Strobel et al, ; Horn, Stelzner, Rudel, & Fraunholz, ). Internalised S .…”

Section: Introductionmentioning

confidence: 99%

“…Staphylococcus aureus invades a variety of non-professional phagocytic cells (NPPC): epithelial and endothelial cells, osteoblasts, fibroblast, keratinocytes, and others (see, for instance, Strobel et al, 2016;Horn, Stelzner, Rudel, & Fraunholz, 2017). Internalised S. aureus can survive within host cells for extended periods (see, e.g., Melly, Thomison, & Rogers, 1960;Hamill, Vann, & Proctor, 1986;Lowy, Fant, Higgins, Ogawa, & Hatcher, 1988;Kubica et al, 2008;Tuchscherr et al, 2011).…”

mentioning

confidence: 99%

In or out: Phagosomal escape ofStaphylococcus aureus

Moldovan

Fraunholz

2019

Cellular Microbiology

View full text Add to dashboard Cite

Staphylococcus aureus is internalised by host cells in vivo, and recent research results suggest that the bacteria use this intracellularity to persist in the host and form a reservoir for recurrent infections. However, in different cells types, the pathogen resorts to alternative strategies to survive phagocytosis and the antimicrobial mechanisms of host cells. In non‐professional phagocytes, S. aureus either escapes the endosome followed by cytoplasmic replication or replicates within autophagosomes. Professional phagocytes possess a limited capacity to kill S. aureus and hence the bacteria, well equipped with immune evasive mechanisms, replicate within the cells, eventually lyse out of the cells and thus persist in a continuous cycle of phagocytosis, host cell death, and bacterial release.

show abstract

Inside job: Staphylococcus aureus host-pathogen interactions

Cited by 170 publications

References 264 publications

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

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

Compartmentalized Encapsulation of Two Antibiotics in Porous Nanoparticles: an Efficient Strategy to Treat Intracellular Infections

In or out: Phagosomal escape ofStaphylococcus aureus

Contact Info

Product

Resources

About