Infection of HeLa cells with
            <scp>
              <i>Chlamydia trachomatis</i>
            </scp>
            inhibits protein synthesis and causes multiple changes to host cell pathways

Ohmer, Michaela; Tzivelekidis, Tina; Niedenführ, Nora; Volceanov-Hahn, Larisa; Barth, Svenja; Vier, Juliane; Börries, Melanie; Busch, Hauke; Kook, Lucas; Biniossek, Martin L.; Schilling, Oliver; Kirschnek, Susanne; Häcker, Georg

doi:10.1111/cmi.12993

Cited by 13 publications

(12 citation statements)

References 56 publications

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“…A Click-iT-reaction was performed as described previously following the manufacturer's instructions (Thermo Fisher Scientific; catalog no. C10269) (38). Briefly, 2 h before harvesting, cells were incubated in methionine-and cystine-free medium (Dulbecco modified Eagle medium [DMEM]; Thermo Fisher Scientific; catalog no.…”

Section: Methodsmentioning

confidence: 99%

Apoptosis Functions in Defense against Infection of Mammalian Cells with Environmental Chlamydiae

2020

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Apoptotic cell death can be an efficient defense reaction of mammalian cells infected with obligate intracellular pathogens; the host cell dies and the pathogen cannot replicate. While this is well established for viruses, there is little experimental support for such a concept in bacterial infections. All Chlamydiales are obligate intracellular bacteria, and different species infect vastly different hosts. Chlamydia trachomatis infects human epithelial cells; Parachlamydia acanthamoebae replicates in amoebae. We here report that apoptosis impedes growth of P. acanthamoebae in mammalian cells. In HeLa human epithelial cells, P. acanthamoebae infection induced apoptosis, which was inhibited when mitochondrial apoptosis was blocked by codeletion of the mediators of mitochondrial apoptosis, Bax and Bak, by overexpression of Bcl-XL or by deletion of the apoptosis initiator Noxa. Deletion of Bax and Bak in mouse macrophages also inhibited apoptosis. Blocking apoptosis permitted growth of P. acanthamoebae in HeLa cells, as measured by fluorescence in situ hybridization, assessment of genome replication and protein synthesis, and the generation of infectious progeny. Coinfection with C. trachomatis inhibited P. acanthamoebae-induced apoptosis, suggesting that the known antiapoptotic activity of C. trachomatis can also block P. acanthamoebae-induced apoptosis. C. trachomatis coinfection could not rescue P. acanthamoebae growth in HeLa; in coinfected cells, C. trachomatis even suppressed the growth of P. acanthamoebae independently of apoptosis, while P. acanthamoebae surprisingly enhanced the growth of C. trachomatis. Our results show that apoptosis can be used in the defense of mammalian cells against obligate intracellular bacteria and suggest that the known antiapoptotic activity of human pathogenic chlamydiae is indeed required to permit their growth in human cells.

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Section: Methodsmentioning

confidence: 99%

Apoptosis Functions in Defense against Infection of Mammalian Cells with Environmental Chlamydiae

2020

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“…In subsequent studies, multiple research groups were able to show that proliferation of certain medically important microorganisms like Shigella, Salmonella, Chlamydia or Legionella within host cells resulted in the inhibition of eukaryotic protein synthesis Formal, 1980, 1981;McCusker et al, 1991;Ohmer et al, 2019). In Shigella and Salmonella, observed cytotoxic effects were attributed to the production of cytotoxins, Shiga or Shigalike toxins by the pathogens (Brown et al, 1980;Koo et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Targeting Eukaryotic mRNA Translation by Legionella pneumophila

Belyi

2020

Front. Mol. Biosci.

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Legionella is a gram-negative microorganism and an infectious agent of pneumonia in humans. It is an intracellular pathogen and multiplies in different eukaryotic cells like amoebae, ciliated protozoa, macrophages, monocytes, and lung epithelial cells. Proliferation of L. pneumophila in eukaryotic cells depends on its type 4 secretion system, which delivers an arsenal of bacterial effector proteins to cytoplasm of its host. Once within the cytoplasm, effectors modify a broad range of host activities, including mRNA translation. Translation is inhibited by Legionella through the action of several effector proteins including Lgt1, Lgt2, Lgt3, SidI, LegK4, SidL, and RavX. Lgt1-3 and SidI target elongation factors: Lgt1-3 mono-glucosylate elongation factor eEF1A, while SidI binds eEF1A, and eEF1Bγ. Effector LegK4 inhibits protein synthesis by phosphorylating Hsp70 proteins, while SidL and RavX have no defined targets in protein synthesis machinery thus far. In addition to direct inhibition of protein synthesis, SidI also affects the stress response, whereas Lgt1-3 -unfolded protein response and cell-cycle progression of host cells. Whether manipulation of these processes is linked to canonical or non-canonical function(s) of targeted elongation factors remains unknown.

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“…Exotoxins (e.g., diphtheria toxin from C. diphtheriae, shiga toxin from S. dysenteriae and exotoxin A from P. aeruginosa) block protein translation by inactivating the host elongation factor 2 (EF2) via ADP-ribosylation [154]. C. trachomatis substantially inhibits host protein synthesis, possibly by inducing ER or mitochondrial stress [155]. L. pneumophila uses several effectors to interfere with host protein translation.…”

Section: Blockade Of Protein Translationmentioning

confidence: 99%

NOD-Like Receptors: Guards of Cellular Homeostasis Perturbation during Infection

Pei

Dorhoi

2021

IJMS

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The innate immune system relies on families of pattern recognition receptors (PRRs) that detect distinct conserved molecular motifs from microbes to initiate antimicrobial responses. Activation of PRRs triggers a series of signaling cascades, leading to the release of pro-inflammatory cytokines, chemokines and antimicrobials, thereby contributing to the early host defense against microbes and regulating adaptive immunity. Additionally, PRRs can detect perturbation of cellular homeostasis caused by pathogens and fine-tune the immune responses. Among PRRs, nucleotide binding oligomerization domain (NOD)-like receptors (NLRs) have attracted particular interest in the context of cellular stress-induced inflammation during infection. Recently, mechanistic insights into the monitoring of cellular homeostasis perturbation by NLRs have been provided. We summarize the current knowledge about the disruption of cellular homeostasis by pathogens and focus on NLRs as innate immune sensors for its detection. We highlight the mechanisms employed by various pathogens to elicit cytoskeleton disruption, organelle stress as well as protein translation block, point out exemplary NLRs that guard cellular homeostasis during infection and introduce the concept of stress-associated molecular patterns (SAMPs). We postulate that integration of information about microbial patterns, danger signals, and SAMPs enables the innate immune system with adequate plasticity and precision in elaborating responses to microbes of variable virulence.

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Infection of HeLa cells with Chlamydia trachomatis inhibits protein synthesis and causes multiple changes to host cell pathways

Cited by 13 publications

References 56 publications

Apoptosis Functions in Defense against Infection of Mammalian Cells with Environmental Chlamydiae

Apoptosis Functions in Defense against Infection of Mammalian Cells with Environmental Chlamydiae

Targeting Eukaryotic mRNA Translation by Legionella pneumophila

NOD-Like Receptors: Guards of Cellular Homeostasis Perturbation during Infection

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