scholarly journals WIPI-1 Positive Autophagosome-Like Vesicles Entrap PathogenicStaphylococcus aureusfor Lysosomal Degradation

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Mario Mauthe ◽  
Wenqi Yu ◽  
Oleg Krut ◽  
Martin Krönke ◽  
Friedrich Götz ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Staphylococcus Aureus ◽  
Cell Division ◽  
Membrane Protein ◽  
Host Cell ◽  
Effector Function ◽  
Host Cells ◽  
Lysosomal Degradation ◽  
Content Analyses ◽  
Confocal And Electron Microscopy

Invading pathogens provoke the autophagic machinery and, in a process termed xenophagy, the host cell survives because autophagy is employed as a safeguard for pathogens that escaped phagosomes. However, some pathogens can manipulate the autophagic pathway and replicate within the niche of generated autophagosome-like vesicles. By automated fluorescence-based high content analyses, we demonstrate thatStaphylococcus aureusstrains (USA300, HG001, SA113) stimulate autophagy and become entrapped in intracellular PtdIns(3)P-enriched vesicles that are decorated with human WIPI-1, an essential PtdIns(3)P effector of canonical autophagy and membrane protein of both phagophores and autophagosomes. Further,agr-positiveS. aureus(USA300, HG001) strains were more efficiently entrapped in WIPI-1 positive autophagosome-like vesicles when compared toagr-negative cells (SA113). By confocal and electron microscopy we provide evidence that single- and multiple-Staphylococci entrapped undergo cell division. Moreover, the number of WIPI-1 positive autophagosome-like vesicles entrapping Staphylococci significantly increased upon (i) lysosomal inhibition by bafilomycin A1and (ii) blocking PIKfyve-mediated PtdIns(3,5)P2generation by YM201636. In summary, our results provide evidence that the PtdIns(3)P effector function of WIPI-1 is utilized during xenophagy ofStaphylococcus aureus. We suggest that invadingS. aureuscells become entrapped in autophagosome-like WIPI-1 positive vesicles targeted for lysosomal degradation in nonprofessional host cells.

scholarly journals A Single-Pass Type I Membrane Protein from the Apicomplexan Parasite Cryptosporidium parvum with Nanomolar Binding Affinity to Host Cell Surface

2021 ◽  
Vol 9 (5) ◽  
pp. 1015
Author(s):  
Tianyu Zhang ◽  
Xin Gao ◽  
Dongqiang Wang ◽  
Jixue Zhao ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Cell Surface ◽  
Host Cell ◽  
Binding Affinity ◽  
Cryptosporidium Parvum ◽  
Host Cells ◽  
Watery Diarrhea ◽  
Type I ◽  
Single Pass ◽  
Host Cell Surface

Cryptosporidium parvum is a globally recognized zoonotic parasite of medical and veterinary importance. This parasite mainly infects intestinal epithelial cells and causes mild to severe watery diarrhea that could be deadly in patients with weakened or defect immunity. However, its molecular interactions with hosts and pathogenesis, an important part in adaptation of parasitic lifestyle, remain poorly understood. Here we report the identification and characterization of a C. parvum T-cell immunomodulatory protein homolog (CpTIPH). CpTIPH is a 901-aa single-pass type I membrane protein encoded by cgd5_830 gene that also contains a short Vibrio, Colwellia, Bradyrhizobium and Shewanella (VCBS) repeat and relatively long integrin alpha (ITGA) N-terminus domain. Immunofluorescence assay confirmed the location of CpTIPH on the cell surface of C. parvum sporozoites. In congruence with the presence of VCBS repeat and ITGA domain, CpTIPH displayed high, nanomolar binding affinity to host cell surface (i.e., Kd(App) at 16.2 to 44.7 nM on fixed HCT-8 and CHO-K1 cells, respectively). The involvement of CpTIPH in the parasite invasion is partly supported by experiments showing that an anti-CpTIPH antibody could partially block the invasion of C. parvum sporozoites into host cells. These observations provide a strong basis for further investigation of the roles of CpTIPH in parasite-host cell interactions.

The cell cycle of symbiotic Chlorella. I. The relationship between host feeding and algal cell growth and division

1985 ◽  
Vol 77 (1) ◽  
pp. 225-239
Author(s):  
P.J. McAuley
Keyword(s):  
Cell Division ◽  
Cell Growth ◽  
Host Cell ◽  
Algal Cell ◽  
Host Cells ◽  
Digestive Cell ◽  
Host Feeding ◽  
Digestive Cells ◽  
Division Factor ◽  
Cell Mitosis

When green hydra were starved, cell division of the symbiotic algae within their digestive cells was inhibited, but algal cell growth, measured as increase in either mean volume or protein content per cell, was not. Therefore, control of algal division by the host digestive cells must be effected by direct inhibition of algal mitosis rather than by controlling algal cell growth. The number of algae per digestive cell increased slightly during starvation, eventually reaching a new stable level. A number of experiments demonstrated that although there was a relationship between host cell and algal mitosis, this was not causal: the apparent entrainment of algal mitosis to that of the host cells could be disrupted. Thus, there was a delay in algal but not host cell mitosis when hydra were fed after prolonged starvation, and algae repopulated starved hydra with lower than normal numbers of algae (reinfected aposymbionts or hydra transferred to light after growth in continuous darkness). Two experiments demonstrated a direct stimulation of algal cell division by host feeding. Relationships of algal and host cell mitosis to numbers of Artemia digested per hydra were different, and in hydra fed extracted Artemia algal, but not host cell, mitosis was reduced in comparison to that in control hydra fed live shrimp. It is proposed that algal division may be dependent on a division factor, derived from host digestion of prey, whose supply is controlled by the host cells. Numbers of algae per cell would be regulated by competition for division factor, except at host cell mitosis, when the algae may have temporarily uncontrolled access to host pools of division factor. The identity of the division factor is not known, but presumably is a metabolite needed by both host cells and algae.

scholarly journals Daptomycin Exerts Bactericidal Activity without Lysis of Staphylococcus aureus

2008 ◽  
Vol 52 (6) ◽  
pp. 2223-2225 ◽  
Author(s):  
Nicole Cotroneo ◽  
Robert Harris ◽  
Nancy Perlmutter ◽  
Terry Beveridge ◽  
Jared A. Silverman
Keyword(s):  
Electron Microscopy ◽  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Division ◽  
Bactericidal Activity ◽  
Membrane Integrity ◽  
Cell Lysis

ABSTRACT The ability of daptomycin to produce bactericidal activity against Staphylococcus aureus while causing negligible cell lysis has been demonstrated using electron microscopy and the membrane integrity probes calcein and ToPro3. The formation of aberrant septa on the cell wall, suggestive of impairment of the cell division machinery, was also observed.

scholarly journals Competitive adherence as a mechanism of bacterial interference

1983 ◽  
Vol 29 (6) ◽  
pp. 700-703 ◽  
Author(s):  
Debra Jan Bibel ◽  
Raza Aly ◽  
Charlene Bayles ◽  
Walter G. Strauss ◽  
Henry R. Shinefield ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Host Cell ◽  
Virulent Strain ◽  
Host Cells ◽  
Aureus Strain ◽  
Attachment Sites ◽  
Specific Attachment ◽  
Mucosal Cells ◽  
Bacterial Interference

To determine whether competition among bacteria for specific attachment sites on host cells can explain bacterial interference, Staphylococcus aureus strain 502A was tested in turn against two different nasal coryneforms, a strain of Pseudomonas aeruginosa, and a virulent strain of S. aureus, all in the presence of nasal mucosal cells. Particularly examined was the influence of sequence in which bacteria were presented to the nasal cells in comparison with initial mixtures and individual suspensions. Results paralleled those observed in clinical prophylaxis: the bacterium first to adhere to the epithelial cells was able, under uniform conditions, to interfere with the colonization of subsequently added bacteria. Secondary adherence was not eliminated but substantially reduced, and was probably related to steric blockage by the initial colonizer and its particular ability to dissociate from the host cell.

scholarly journals Intracellular Staphylococcus aureus employs the cysteine protease staphopain A to induce host cell death in epithelial cells

2020 ◽  
Author(s):  
Kathrin Stelzner ◽  
Tobias Hertlein ◽  
Aneta Sroka ◽  
Adriana Moldovan ◽  
Kerstin Paprotka ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Death ◽  
Epithelial Cells ◽  
Host Cell ◽  
Cysteine Protease ◽  
Host Cells ◽  
Upper Respiratory Tract ◽  
Intracellular Replication ◽  
Tissue Destruction ◽  
Host Cell Death

AbstractStaphylococcus 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 SummaryStaphylococcus 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.

scholarly journals Study of Staphylococcus aureus Biofilm Ability to Destroy Bone Matrix in Absences of Host Immunity

2020 ◽  
Author(s):  
ahmed Al Ghaithi ◽  
Sultan Al Mastari ◽  
John Husband ◽  
Mohammed al kindi ◽  
Atika Al Bimani
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Staphylococcus Aureus ◽  
Raman Spectroscopy ◽  
Immune System ◽  
Bone Resorption ◽  
Bone Quality ◽  
Host Cells ◽  
Immune System Activation ◽  
Scanning Electron

AbstractPurposeOsteomyelitis is an infectious bone process leading to bone necrosis and destruction. Published reports on pathogen biofilm thus far have focused on indirect bone resorption mediated by host cells and factors secondary to immune system activation. However, direct bone resorption due to biofilm pathogen has not been adequately studied yet. This study aims to investigate the effect of biofilm pathogen in ex-vivo human bones in the absence of the host immune response using Raman spectroscopy and Scanning electron microscopy.MethodsBone samples collected from patients who underwent knee replacement surgeries were inoculated with Staphylococcus aureus bacteria. Bacterial direct effects on the bone quality were then examined, at various time intervals, using Raman spectroscopy and scanning electron microscopy.ResultsRaman spectroscopy and scanning electron demonstrated the destruction of bone structure and drop in bone quality.ConclusionThis experiment shows the direct effect of bacteria on bone during osteomyelitis in addition to the recognised destruction caused by the host immune system.

scholarly journals Selective Host Cell Death by Staphylococcus aureus: A Strategy for Bacterial Persistence

2021 ◽  
Vol 11 ◽  
Author(s):  
Dominique Missiakas ◽  
Volker Winstel
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Death ◽  
Host Cell ◽  
Intervention Strategies ◽  
Host Cells ◽  
Intracellular Killing ◽  
Mammalian Development ◽  
Cell Responses ◽  
Cell Death Pathways ◽  
Host Cell Death

Host cell death programs are fundamental processes that shape cellular homeostasis, embryonic development, and tissue regeneration. Death signaling and downstream host cell responses are not only critical to guide mammalian development, they often act as terminal responses to invading pathogens. Here, we briefly review and contrast how invading pathogens and specifically Staphylococcus aureus manipulate apoptotic, necroptotic, and pyroptotic cell death modes to establish infection. Rather than invading host cells, S. aureus subverts these cells to produce diffusible molecules that cause death of neighboring hematopoietic cells and thus shapes an immune environment conducive to persistence. The exploitation of cell death pathways by S. aureus is yet another virulence strategy that must be juxtaposed to mechanisms of immune evasion, autophagy escape, and tolerance to intracellular killing, and brings us closer to the true portrait of this pathogen for the design of effective therapeutics and intervention strategies.

scholarly journals Nonprofessional Phagocytic Cell Receptors Involved inStaphylococcus aureusInternalization

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Nayeli Alva-Murillo ◽  
Joel Edmundo López-Meza ◽  
Alejandra Ochoa-Zarzosa
Keyword(s):  
Staphylococcus Aureus ◽  
Host Cell ◽  
Soft Tissues ◽  
Scavenger Receptor ◽  
Host Cells ◽  
Phagocytic Cell ◽  
Phagocytic Cells ◽  
Cell Receptors ◽  
Life Threatening ◽  
Bacterial Effectors

Staphylococcus aureusis a successful human and animal pathogen. The majority of infections caused by this pathogen are life threatening, primarily becauseS. aureushas developed multiple evasion strategies, possesses intracellular persistence for long periods, and targets the skin and soft tissues. Therefore, it is very important to understand the mechanisms employed byS. aureusto colonize and proliferate in these cells. The aim of this review is to describe the recent discoveries concerning the host receptors of nonprofessional phagocytes involved inS. aureusinternalization. Most of the knowledge related to the interaction ofS. aureuswith its host cells has been described in professional phagocytic cells such as macrophages. Here, we showed that in nonprofessional phagocytes theα5β1 integrin host receptor, chaperons, and the scavenger receptor CD36 are the main receptors employed duringS. aureusinternalization. The characterization and identification of new bacterial effectors and the host cell receptors involved will undoubtedly lead to new discoveries with beneficial purposes.

scholarly journals Quantitative Analysis of Gentamicin, Azithromycin, Telithromycin, Ciprofloxacin, Moxifloxacin, and Oritavancin (LY333328) Activities against Intracellular Staphylococcus aureus in Mouse J774 Macrophages

2003 ◽  
Vol 47 (7) ◽  
pp. 2283-2292 ◽  
Author(s):  
Cristina Seral ◽  
Françoise Van Bambeke ◽  
Paul M. Tulkens
Keyword(s):  
Electron Microscopy ◽  
Staphylococcus Aureus ◽  
Quantitative Analysis ◽  
Strain Atcc ◽  
Cellular Accumulation ◽  
Intracellular Activity ◽  
Infected Cells ◽  
Intracellular Activities ◽  
Extracellular Activity ◽  
Confocal And Electron Microscopy

ABSTRACT Using J774 macrophages, the intracellular activities of gentamicin, azithromycin, telithromycin, ciprofloxacin, moxifloxacin, and oritavancin (LY333328) against Staphylococcus aureus (strain ATCC 25923) have been quantitatively assessed in a 24-h model. S. aureus was positively localized in phagolysosomes by confocal and electron microscopy, and extracellular growth was prevented with 0.5 mg of gentamicin/liter (1× MIC) in controls. When tested at extracellular concentrations equivalent to their maximum concentrations in human serum, all antibiotics except azithromycin caused a significant reduction of the postphagocytosis inoculum within 24 h, albeit to markedly different extents (telithromycin [2 mg/liter], 0.60 log; ciprofloxacin [4.3 mg/liter], 0.81 log; gentamicin [18 mg/liter], 1.21 log; moxifloxacin [4 mg/liter], 1.51 log; oritavancin [25 mg/liter], 3.49 log). Intracellular activities were not systematically related to drug accumulation (apparent cellular-to-extracellular concentration ratios in infected cells: ciprofloxacin, 3.2; gentamicin, 6.8; telithromycin, 8.7; moxifloxacin, 13.4; azithromycin, 50; oritavancin, 348). Intracellular activity was not directly correlated to extracellular activity as measured in broth. Conditions of pH 5 (i.e., mimicking that of phagolysosomes) markedly reduced the activity of gentamicin, azithromycin, and telithromycin (≥32×) and fairly extensively reduced that of ciprofloxacin and moxifloxacin (≥4×) but did not affect oritavancin activity. We conclude that the cellular accumulation of antibiotics is not the only parameter to take into account for intracellular activity but that local environmental conditions (such as pH) and other factors can also prove critical.

Sign in / Sign up

Export Citation Format

Share Document