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Intracellular Bacteria

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1. A Mycobacterium avium subsp. paratuberculosis relA deletion mutant and a 35 kDa major membrane protein elicit development of cytotoxic T lymphocytes with ability to kill intracellular bacteria (PubMed)

A Mycobacterium avium subsp. paratuberculosis relA deletion mutant and a 35 kDa major membrane protein elicit development of cytotoxic T lymphocytes with ability to kill intracellular bacteria Efforts to develop live attenuated vaccines against Mycobacterium avium subspecies paratuberculosis (Map), using indirect methods to screen Map deletion mutants for potential efficacy, have not been successful. A reduction in the capacity to survive in macrophages has not predicted the ability of mutants (...) culture assays for analysis and evaluation of cytotoxic T cells generated against ΔMap/relA or MMP. Analysis of the effector activity of responding cells revealed the reason ΔMap/relA could not establish a persistent infection was that vaccination elicited development of cytotoxic CD8 T cells (CTL) with the capacity to kill intracellular bacteria. We demonstrated the same CTL response could be elicited with two rounds of antigenic stimulation of APC pulsed with ΔMap/relA or MMP ex vivo. Cytotoxicity

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2018 Veterinary Research

2. Mitochondrial fragmentation affects neither the sensitivity to TNFα-induced apoptosis of Brucella-infected cells nor the intracellular replication of the bacteria (PubMed)

Mitochondrial fragmentation affects neither the sensitivity to TNFα-induced apoptosis of Brucella-infected cells nor the intracellular replication of the bacteria Mitochondria are complex organelles that participate in many cellular functions, ranging from ATP production to immune responses against viruses and bacteria. This integration of a plethora of functions within a single organelle makes mitochondria a very attractive target to manipulate for intracellular pathogens. We characterised

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2018 Scientific reports

3. Pathogenic mechanisms of intracellular bacteria. (PubMed)

Pathogenic mechanisms of intracellular bacteria. We wished to overview recent data on a subset of epigenetic changes elicited by intracellular bacteria in human cells. Reprogramming the gene expression pattern of various host cells may facilitate bacterial growth, survival, and spread.DNA-(cytosine C5)-methyltransferases of Mycoplasma hyorhinis targeting cytosine-phosphate-guanine (CpG) dinucleotides and a Mycobacterium tuberculosis methyltransferase targeting non-CpG sites methylated the host (...) a cellular gene, whereas Mycobacterium leprae altered the epigenotype, phenotype, and fate of infected Schwann cells. The 'keystone pathogen' oral bacterium Porphyromonas gingivalis induced local DNA methylation and increased the level of histone acetylation in host cells. These epigenetic changes at the biofilm-gingiva interface may contribute to the development of periodontitis.Epigenetic regulators produced by intracellular bacteria alter the epigenotype and gene expression pattern of host cells

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2017 Current Opinion in Infectious Diseases

4. An analysis of surface proteomics results reveals novel candidates for intracellular/surface moonlighting proteins in bacteria.

An analysis of surface proteomics results reveals novel candidates for intracellular/surface moonlighting proteins in bacteria. Proteins expressed on the bacterial cell surface play important roles in infection and virulence and can be targets for vaccine development or used as biomarkers. Surprisingly, an increasing number of surface proteins are being found to be identical to intracellular enzymes and chaperones, and a few dozen intracellular/surface moonlighting proteins have been found (...) that have different functions inside the cell and on the cell surface. The results of twenty-two published bacterial surface proteomics studies were analyzed using bioinformatics tools to consider how many additional intracellular proteins are also found on the cell surface. More than 1000 out of the 3619 proteins observed on the cell surface lack the transmembrane alpha-helices or transmembrane beta-barrels found in integral membrane proteins and also lack the signal peptides found in proteins secreted

2017 Molecular bioSystems

5. HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes (PubMed)

HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes Recent evidence on HDAC6 function underlines its role as a key protein in the innate immune response to viral infection. However, whether HDAC6 regulates innate immunity during bacterial infection remains unexplored. To assess the role of HDAC6 in the regulation of defence mechanisms against intracellular bacteria, we used the Listeria monocytogenes (Lm) infection (...) to be caused by a defect in autophagy. Hence, Hdac6-/- BMDCs accumulate higher levels of the autophagy marker p62 and show defective phagosome-lysosome fusion. These data underline the important function of HDAC6 in dendritic cells not only in bacterial autophagy, but also in the proper activation of TLR signalling. These results thus demonstrate an important regulatory role for HDAC6 in the innate immune response to intracellular bacterial infection.

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2017 PLoS pathogens

6. Peptidoglycan in obligate intracellular bacteria (PubMed)

Peptidoglycan in obligate intracellular bacteria Peptidoglycan is the predominant stress-bearing structure in the cell envelope of most bacteria, and also a potent stimulator of the eukaryotic immune system. Obligate intracellular bacteria replicate exclusively within the interior of living cells, an osmotically protected niche. Under these conditions peptidoglycan is not necessarily needed to maintain the integrity of the bacterial cell. Moreover, the presence of peptidoglycan puts bacteria (...) tsutsugamushi, Wolbachia and Anaplasma marginale. This grouping is likely to reflect biological differences in their infection cycle compared with peptidoglycan-negative obligate intracellular bacteria such as Ehrlichia and Anaplasma phagocytophilum, as well as obligate intracellular bacteria with classical peptidoglycan such as Coxiella, Buchnera and members of the Rickettsia genus. The signature gene set of the peptidoglycan-intermediate group reveals insights into minimal enzymatic requirements

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2017 Molecular microbiology

7. How to rewire the host cell: A home improvement guide for intracellular bacteria (PubMed)

How to rewire the host cell: A home improvement guide for intracellular bacteria Intracellular bacterial pathogens have developed versatile strategies to generate niches inside the eukaryotic cells that allow them to survive and proliferate. Making a home inside the host offers many advantages; however, intracellular bacteria must also overcome many challenges, such as disarming innate immune signaling and accessing host nutrient supplies. Gaining entry into the cell and avoiding degradation (...) is only the beginning of a successful intracellular lifestyle. To establish these replicative niches, intracellular pathogens secrete various virulence proteins, called effectors, to manipulate host cell signaling pathways and subvert host defense mechanisms. Many effectors mimic host enzymes, whereas others perform entirely novel enzymatic functions. A large volume of work has been done to understand how intracellular bacteria manipulate membrane trafficking pathways. In this review, we focus on how

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2017 The Journal of cell biology

8. The E3 ubiquitin ligase NEDD4 enhances killing of membrane-perturbing intracellular bacteria by promoting autophagy (PubMed)

The E3 ubiquitin ligase NEDD4 enhances killing of membrane-perturbing intracellular bacteria by promoting autophagy The E3 ubiquitin ligase NEDD4 has been intensively studied in processes involved in viral infections, such as virus budding. However, little is known about its functions in bacterial infections. Our investigations into the role of NEDD4 in intracellular bacterial infections demonstrate that Mycobacterium tuberculosis and Listeria monocytogenes, but not Mycobacterium bovis BCG (...) , replicate more efficiently in NEDD4 knockdown macrophages. In parallel, NEDD4 knockdown or knockout impaired basal macroautophagy/autophagy, as well as infection-induced autophagy. Conversely, NEDD4 expression promoted autophagy in an E3 catalytic activity-dependent manner, thereby restricting intracellular Listeria replication. Mechanistic studies uncovered that endogenous NEDD4 interacted with BECN1/Beclin 1 and this interaction increased during Listeria infection. Deficiency of NEDD4 resulted

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2017 Autophagy

9. Manipulation of Host Cholesterol by Obligate Intracellular Bacteria (PubMed)

Manipulation of Host Cholesterol by Obligate Intracellular Bacteria Cholesterol is a multifunctional lipid that plays important metabolic and structural roles in the eukaryotic cell. Despite having diverse lifestyles, the obligate intracellular bacterial pathogens Chlamydia, Coxiella, Anaplasma, Ehrlichia, and Rickettsia all target cholesterol during host cell colonization as a potential source of membrane, as well as a means to manipulate host cell signaling and trafficking. To promote host (...) cell entry, these pathogens utilize cholesterol-rich microdomains known as lipid rafts, which serve as organizational and functional platforms for host signaling pathways involved in phagocytosis. Once a pathogen gains entrance to the intracellular space, it can manipulate host cholesterol trafficking pathways to access nutrient-rich vesicles or acquire membrane components for the bacteria or bacteria-containing vacuole. To acquire cholesterol, these pathogens specifically target host cholesterol

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2017 Frontiers in cellular and infection microbiology

10. Engineering of obligate intracellular bacteria: progress, challenges and paradigms (PubMed)

Engineering of obligate intracellular bacteria: progress, challenges and paradigms It is estimated that approximately one billion people are at risk of infection with obligate intracellular bacteria, but little is known about the underlying mechanisms that govern their life cycles. The difficulty in studying Chlamydia spp., Coxiella spp., Rickettsia spp., Anaplasma spp., Ehrlichia spp. and Orientia spp. is, in part, due to their genetic intractability. Recently, genetic tools have been (...) developed; however, optimizing the genomic manipulation of obligate intracellular bacteria remains challenging. In this Review, we describe the progress in, as well as the constraints that hinder, the systematic development of a genetic toolbox for obligate intracellular bacteria. We highlight how the use of genetically manipulated pathogens has facilitated a better understanding of microbial pathogenesis and immunity, and how the engineering of obligate intracellular bacteria could enable the discovery

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2017 Nature reviews. Microbiology

11. T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria (PubMed)

T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria Th1 cells can be activated by TCR-independent stimuli, but the importance of this pathway in vivo and the precise mechanisms involved require further investigation. Here, we used a simple model of non-cognate Th1 cell stimulation in Salmonella-infected mice to examine these issues. CD4 Th1 cell expression of both IL-18R and DR3 was required for optimal IFN-γ (...) is a critical element of efficient bacterial clearance. Thus, IL-18R and DR3 are critical players in non-cognate stimulation of Th1 cells and this response plays an important role in protection against intracellular bacteria.

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2017 PLoS pathogens

12. Boeravinone B, A Novel Dual Inhibitor of NorA Bacterial Efflux Pump of Staphylococcus aureus and Human P-Glycoprotein, Reduces the Biofilm Formation and Intracellular Invasion of Bacteria (PubMed)

Boeravinone B, A Novel Dual Inhibitor of NorA Bacterial Efflux Pump of Staphylococcus aureus and Human P-Glycoprotein, Reduces the Biofilm Formation and Intracellular Invasion of Bacteria This study elucidated the role of boeravinone B, a NorA multidrug efflux pump inhibitor, in biofilm inhibition. The effects of boeravinone B plus ciprofloxacin, a NorA substrate, were evaluated in NorA-overexpressing, wild-type, and knocked-out Staphylococcus aureus (SA-1199B, SA-1199, and SA-K1758 (...) , respectively). The mechanism of action was confirmed using the ethidium bromide accumulation and efflux assay. The role of boeravinone B as a human P-glycoprotein (P-gp) inhibitor was examined in the LS-180 (colon cancer) cell line. Moreover, its role in the inhibition of biofilm formation and intracellular invasion of S. aureus in macrophages was studied. Boeravinone B reduced the minimum inhibitory concentration (MIC) of ciprofloxacin against S. aureus and its methicillin-resistant strains; the effect

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2017 Frontiers in microbiology

13. Unexpected genomic features in widespread intracellular bacteria: evidence for motility of marine chlamydiae (PubMed)

Unexpected genomic features in widespread intracellular bacteria: evidence for motility of marine chlamydiae Chlamydiae are obligate intracellular bacteria comprising important human pathogens and symbionts of protists. Molecular evidence indicates a tremendous diversity of chlamydiae particularly in marine environments, yet our current knowledge is based mainly on terrestrial representatives. Here we provide first insights into the biology of marine chlamydiae representing three divergent

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2017 The ISME journal

14. Dual functionality nanobioconjugates targeting intracellular bacteria in cancer cells with enhanced antimicrobial activity (PubMed)

Dual functionality nanobioconjugates targeting intracellular bacteria in cancer cells with enhanced antimicrobial activity Bacterial drug resistance has emerged as a serious global threat mandating the development of novel methodologies that allow facile modulation of antimicrobial action in a controlled fashion. Conjugating antibiotics to nanoparticles helps to meet this goal by increasing the drug's overall avidity, bioavailability and easier internalisation into mammalian cells, targeting (...) bacteria that otherwise escape antibacterial action by host cell-localisation. We used polymyxin B sulfate (PMB) and sushi peptide as model drugs against Gram-negative bacteria and established their enhanced antimicrobial activity on Escherichia coli (E. coli) cells after conjugation to gold nanoparticles (AuNPs). The efficacy of the bioconjugates was also tested on Salmonella typhi (S. typhi) bacteria infected into cervical cancer cells (HeLa) and further improved through specific targeting via folate

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2017 Scientific reports

15. Ubiquitination of Innate Immune Regulator TRAF3 Orchestrates Expulsion of Intracellular Bacteria by Exocyst Complex (PubMed)

Ubiquitination of Innate Immune Regulator TRAF3 Orchestrates Expulsion of Intracellular Bacteria by Exocyst Complex Although the intracellular trafficking system is integral to most physiologic activities, its role in mediating immune responses to infection has remained elusive. Here, we report that infected bladder epithelial cells (BECs) mobilized the exocyst complex, a powerful exporter of subcellular vesicles, to rapidly expel intracellular bacteria back for clearance. Toll-like receptor (...) (TLR) 4 signals emanating from bacteria-containing vesicles (BCVs) were found to trigger K33-linked polyubiquitination of TRAF3 at Lys168, which was then detected by RalGDS, a guanine nucleotide exchange factor (GEF) that precipitated the assembly of the exocyst complex. Although this distinct modification of TRAF3 served to connect innate immune signaling to the cellular trafficking apparatus, it crucially ensured temporal and spatial accuracy in determining which among the many subcellular

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2016 Immunity

16. LL37:DNA complexes provide antimicrobial activity against intracellular bacteria in human macrophages (PubMed)

LL37:DNA complexes provide antimicrobial activity against intracellular bacteria in human macrophages As part of the innate host response neutrophils release neutrophil extracellular traps (NETs), protein:DNA complexes that contain a number of antimicrobial peptides (AMPs), such as cathelicidin. Human cathelicidin in its active form, LL37, has potent antimicrobial activity against bacteria. However, whether LL37 derived from NETs contributes to antimicrobial activity against intracellular (...) defence against intracellular bacteria in human macrophages.© 2016 John Wiley & Sons Ltd.

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2016 Immunology

17. Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis (PubMed)

Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis Inflammasomes activate caspase-1 in response to cytosolic contamination or perturbation. This inflammatory caspase triggers the opening of the GSDMD pore in the plasma membrane, resulting in lytic cell death called pyroptosis. We had previously assumed that pyroptosis releases intracellular bacteria to the extracellular space. Here, we find that viable bacteria instead (...) remain trapped within the cellular debris of pyroptotic macrophages. This trapping appears to be an inevitable consequence of how osmotic lysis ruptures the plasma membrane, and may also apply to necroptosis and some forms of nonprogrammed necrosis. Although membrane tears release soluble cytosolic contents, they are small enough to retain organelles and bacteria. We call this structure the pore-induced intracellular trap (PIT), which is conceptually parallel to the neutrophil extracellular trap (NET

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2016 The Journal of experimental medicine

18. Live imaging of the genetically intractable obligate intracellular bacteria Orientia tsutsugamushi using a panel of fluorescent dyes (PubMed)

Live imaging of the genetically intractable obligate intracellular bacteria Orientia tsutsugamushi using a panel of fluorescent dyes Our understanding of the molecular mechanisms of bacterial infection and pathogenesis are disproportionally derived from a small number of well-characterised species and strains. One reason for this is the enormous time and resources required to develop a new organism into experimental system that can be interrogated at the molecular level, in particular

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2016 Journal of microbiological methods

19. Intracellular Bacteria

Intracellular Bacteria Intracellular Bacteria Toggle navigation Brain Head & Neck Chest Endocrine Abdomen Musculoskeletal Skin Infectious Disease Hematology & Oncology Cohorts Diagnostics Emergency Findings Procedures Prevention & Management Pharmacy Resuscitation Trauma Emergency Procedures Ultrasound Cardiovascular Emergencies Lung Emergencies Infectious Disease Pediatrics Neurologic Emergencies Skin Exposure Miscellaneous Abuse Cancer Administration 4 Intracellular Bacteria Intracellular (...) Bacteria Aka: Intracellular Bacteria , Obligate Intracellular Bacteria , Intracellular Pathogen , Intracellular Fungi , Intracellular Protozoa From Related Chapters II. Types: Bacterial Obligate Intracellular Parasites (except ) III. Types: Bacterial Optional Intracellular Parasites Other species and other species Rhodococcus equi IV. Types: Intracellular Fungi V. Types: Intracellular Protozoa Trypanomsoma cruzi Toxplasma VI. Types: Intracellular Viruses All viruses are obligate intracellular s VII

2018 FP Notebook

20. Saliva induces expression of antimicrobial peptides and promotes intracellular killing of bacteria in keratinocytes by EGFR-transactivation. (PubMed)

Saliva induces expression of antimicrobial peptides and promotes intracellular killing of bacteria in keratinocytes by EGFR-transactivation. Wounds in the oral cavity, constantly exposed to both saliva and bacteria, heal quickly without infection. Furthermore, during licking of skin wounds, saliva promotes wound healing and plays a role in keeping the wound free of infection.To investigate whether saliva induces expression of antimicrobial peptides (AMPs) in human epidermal keratinocytes (...) and whether saliva promotes clearance of intracellular bacteria in these cells.Expression of AMPs was investigated in the oral mucosa and ex vivo injured skin by immunohistochemistry. Human beta-defensin-3 expression was investigated in epidermal keratinocytes after saliva stimulation, using real-time polymerase chain reaction and immunofluorescence.We found higher expression of AMPs in the oral mucosa than in the epidermis. Saliva accelerated the injury-induced expression of AMPs in human skin ex vivo

2016 British Journal of Dermatology

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