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Intracellular Bacteria

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1. Persistent Intracellular Staphylococcus aureus in Keratinocytes Lead to Activation of the Complement System with Subsequent Reduction in the Intracellular Bacterial Load Full Text available with Trip Pro

Persistent Intracellular Staphylococcus aureus in Keratinocytes Lead to Activation of the Complement System with Subsequent Reduction in the Intracellular Bacterial Load The complement system is an ancient part of the innate immune system important for both tissue homeostasis and host defense. However, bacteria like Staphylococcus aureus (SA) possess elaborative mechanisms for evading both the complement system and other parts of the immune system. One of these evasive mechanisms-important (...) dermatitis patients analyzed by bacterial culture and microscopy, demonstrated that SA colonization was associated with the presence of intracellular bacteria and deposition of the TCC in epidermis in vivo. Complement activation on keratinocytes with persistent intracellular bacteria was found with sera deficient/depleted of the complement components C1q, Mannan-binding lectin, or complement factor B, demonstrating involvement of more than one complement activation pathway. Viable bacterial counts showed

2018 Frontiers in immunology

2. Purification of Intracellular Bacterial Communities during Experimental Urinary Tract Infection Reveals an Abundant and Viable Bacterial Reservoir Full Text available with Trip Pro

to form intracellular collections (termed intracellular bacterial communities [IBCs]) within the epithelial cells lining the bladder lumen. IBCs are seen in both infected mice and humans and are a potential cause of recurrent UTI. Genetic and molecular studies of IBCs have been hampered both by the low number of bacteria in IBCs relative to the number extracellular bacteria and by population bottlenecks that occur during IBC formation. We now report the development of a simple and rapid technique (...) Purification of Intracellular Bacterial Communities during Experimental Urinary Tract Infection Reveals an Abundant and Viable Bacterial Reservoir Urinary tract infections (UTIs) are a major infection of humans, particularly affecting women. Recurrent UTIs can cause significant discomfort and expose patients to high levels of antibiotic use, which in turn contributes to the development of higher antibiotic resistance rates. Most UTIs are caused by uropathogenic Escherichia coli, which is able

2018 Infection and immunity

3. Apoptosis inhibition by intracellular bacteria and its consequence on host immunity. (Abstract)

. Conversely, many obligate intracellular bacterial pathogens and some facultative-intracellular bacteria inhibit apoptosis, preventing efferocytosis, and evading innate host defenses. The molecular mechanism of bacterial effectors includes secreted proteins that bind to and inhibit apoptosis cell signaling pathways. We provide an overview of the known bacterial effectors, their host cell targets and their importance for the virulence of human pathogens.Copyright © 2019 Elsevier Ltd. All rights reserved. (...) Apoptosis inhibition by intracellular bacteria and its consequence on host immunity. Regulated cell death via apoptosis not only is important for organismal homeostasis but also serves as an innate defense mechanism. The engulfment of apoptotic infected cells, a process known as efferocytosis, is a common pathway for the destruction of many intracellular bacteria. Some pathogens take advantage of efferocytosis to prevent activation of macrophages and thereby facilitate their dissemination

2019 Current opinion in immunology

4. Metabolic reprogramming: an innate cellular defence mechanism against intracellular bacteria? (Abstract)

Metabolic reprogramming: an innate cellular defence mechanism against intracellular bacteria? The limited metabolic resources of a cell represent an intriguing 'conflict of interest' during host-pathogen interactions, as the battle for nutrients might determine the outcome of an infection. To adapt their metabolic needs, innate immune cells such as monocytes, macrophages or dendritic cells reprogram their metabolism upon activation by microbial compounds. In turn, infection by intracellular (...) bacteria provokes metabolic alterations of the host cell that benefit the pathogen. Here, we discuss the state-of-the-art knowledge on metabolic reprogramming of host cells upon activation or infection with intracellular bacteria. The study of the host-driven and pathogen-driven metabolic alterations that seem to co-exist during infection is an emerging field that will define the metabolic pathways that might be targeted to combat infection.Copyright © 2019 Elsevier Ltd. All rights reserved.

2019 Current opinion in immunology

5. 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 Full Text available with Trip Pro

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

2017 Frontiers in microbiology

6. Intracellular Bacterial Infections: A Challenge for Developing Cellular Mediated Immunity Vaccines for Farmed Fish Full Text available with Trip Pro

in aquaculture is largely attributed to empirical vaccine designs based on inactivation of whole cell (WCI) bacteria vaccines. However, an upcoming challenge in vaccine design is the increase of intracellular bacterial pathogens that are not responsive to WCI vaccines. Intracellular bacterial vaccines evoke cellular mediated immune (CMI) responses that “kill” and eliminate infected cells, unlike WCI vaccines that induce humoral immune responses whose protective mechanism is neutralization (...) Intracellular Bacterial Infections: A Challenge for Developing Cellular Mediated Immunity Vaccines for Farmed Fish Aquaculture is one of the most rapidly expanding farming systems in the world. Its rapid expansion has brought with it several pathogens infecting different fish species. As a result, there has been a corresponding expansion in vaccine development to cope with the increasing number of infectious diseases in aquaculture. The success of vaccine development for bacterial diseases

2018 Microorganisms

7. Francisella tularensis D-Ala D-Ala Carboxypeptidase DacD Is Involved in Intracellular Replication and It Is Necessary for Bacterial Cell Wall Integrity Full Text available with Trip Pro

Francisella tularensis D-Ala D-Ala Carboxypeptidase DacD Is Involved in Intracellular Replication and It Is Necessary for Bacterial Cell Wall Integrity D-alanyl-D-alanine carboxypeptidase, product of dacD gene in Francisella, belongs to penicillin binding proteins (PBPs) and is involved in remodeling of newly synthetized peptidoglycan. In E. coli, PBPs are synthetized in various growth phases and they are able to substitute each other to a certain extent. The DacD protein was found (...) to be accumulated in fraction enriched in membrane proteins from severely attenuated dsbA deletion mutant strain. It has been presumed that the DsbA is not a virulence factor by itself but that its substrates, whose correct folding and topology are dependent on the DsbA oxidoreductase and/or isomerase activities, are the primary virulence factors. Here we demonstrate that Francisella DacD is required for intracellular replication and virulence in mice. The dacD insertion mutant strain showed higher sensitivity

2018 Frontiers in cellular and infection microbiology

8. Runx3 Mediates Resistance to Intracellular Bacterial Infection by Promoting IL12 Signaling in Group 1 ILC and NCR+ILC3 Full Text available with Trip Pro

Runx3 Mediates Resistance to Intracellular Bacterial Infection by Promoting IL12 Signaling in Group 1 ILC and NCR+ILC3 Innate lymphoid cells (ILCs) are the most recently identified family of the innate immune system and are hypothesized to modulate immune functions prior to the generation of adaptive immune responses. Subsets of ILCs reside in the mucosa and regulate immune responses to external pathogens; however, their role and the mechanism by which they protect against intracellular (...) bacterial infection is not completely understood. In this report, using S. typhimurium and L. monocytogenes, we found that the levels of group 1 ILCs and NCR+ ILC3s were increased upon infection and that these increases were associated with Runt-related transcription factor 3 (Runx3) expression. Runx3 fl/fl PLZF-cre mice were much more sensitive to infection with the intracellular bacterial pathogens S. typhimurium and L. monocytogenes partially due to abnormal Group 1 ILC and NCR+ILC3 function. We also

2018 Frontiers in immunology

9. Transient Nutrient Deprivation Promotes Macropinocytosis-Dependent Intracellular Bacterial Community Development Full Text available with Trip Pro

Transient Nutrient Deprivation Promotes Macropinocytosis-Dependent Intracellular Bacterial Community Development Nutrient limitation restricts bacterial growth in privileged sites such as the middle ear. Transient heme-iron restriction of nontypeable Haemophilus influenzae (NTHI), the major causative agent of chronic and recurrent otitis media (OM), promotes new and diverse phenotypes that can influence planktonic, biofilm, and intracellular lifestyles of NTHI. However, the bacterial responses (...) to nutrient restriction that impact intracellular fate and survival of NTHI are unknown. In this work, we provide evidence for the role of transient heme-iron restriction in promoting the formation of intracellular bacterial communities (IBCs) of NTHI both in vitro and in vivo in a preclinical model of OM. We show that transient heme-iron restriction of NTHI results in significantly increased invasion and intracellular populations that escape or evade the endolysosomal pathway for increased intracellular

2018 mSphere

10. Intracellular membranes of bacterial endospores are reservoirs for spore core membrane expansion during spore germination Full Text available with Trip Pro

Intracellular membranes of bacterial endospores are reservoirs for spore core membrane expansion during spore germination Bacterial endospores are formed by certain bacteria, such as Bacillus subtilis or the pathogenic Bacillus anthracis and Clostridioides difficile, to allow survival in environmental conditions which are lethal to vegetative bacteria. The spores possess a particular architecture and molecular inventory which endow them with a remarkable resistance against desiccation, heat (...) as more or less compressed vesicles or tubules within the dormant spore core. Investigations of spores from different species suggest that these intracellular membrane structures below the core membrane are a general feature of endospore forming bacteria.

2018 Scientific reports

11. Male infertility: the intracellular bacterial hypothesis Full Text available with Trip Pro

Male infertility: the intracellular bacterial hypothesis Infertility is a disease that affects one in seven couples. As male infertility affects approximately 30% of these couples with an unknown cause in half the cases, it represents a major public health concern. The classic treatment of male infertility involves intrauterine insemination, with modest outcome, and in vitro fertilization with intracytoplasmic sperm injection, which is known to be invasive and expensive, without treating (...) . The potential negative impact of these bacteria on male fertility might not only involve semen parameters but also, as with C. trachomatis, include important physiological mechanisms such as fertilization processes that are not routinely assessed during infertility investigation. Basic research is important to help determine the exact effect of these bacteria on male fertility to develop targeted treatment and go beyond in vitro fertilization with intracytoplasmic sperm injection.

2018 New Microbes and New Infections

12. Microevolution in response to transient heme-iron restriction enhances intracellular bacterial community development and persistence Full Text available with Trip Pro

Microevolution in response to transient heme-iron restriction enhances intracellular bacterial community development and persistence Bacterial pathogens must sense, respond and adapt to a myriad of dynamic microenvironmental stressors to survive. Adaptation is key for colonization and long-term ability to endure fluctuations in nutrient availability and inflammatory processes. We hypothesize that strains adapted to survive nutrient deprivation are more adept for colonization and establishment (...) of middle ear fluid. In contrast to this clinical paradigm, we observed that the icc mutant strain formed significantly more intracellular bacterial communities (IBCs) than the parental strain early during experimental OM. Although the number of IBCs formed by the parental strain was low at early stages of OM, we observed a significant increase at later stages that coincided with absence of recoverable effusion, suggesting the presence of a mucosal reservoir following resolution of clinical disease

2018 PLoS pathogens

13. GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections Full Text available with Trip Pro

GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain; however, the roles of GABA in antimicrobial host defenses are largely unknown. Here we demonstrate that GABAergic activation enhances antimicrobial responses against intracellular bacterial infection. Intracellular bacterial infection decreases GABA levels in vitro in macrophages and in vivo in sera (...) . Treatment of macrophages with GABA or GABAergic drugs promotes autophagy activation, enhances phagosomal maturation and antimicrobial responses against mycobacterial infection. In macrophages, the GABAergic defense is mediated via macrophage type A GABA receptor (GABAAR), intracellular calcium release, and the GABA type A receptor-associated protein-like 1 (GABARAPL1; an Atg8 homolog). Finally, GABAergic inhibition increases bacterial loads in mice and zebrafish in vivo, suggesting that the GABAergic

2018 Nature communications

14. Heparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages Full Text available with Trip Pro

Heparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages Iron is a crucial micronutrient for both mammals and their associated pathogens, and extensive literature has shown that Mycobacterium tuberculosis (Mtb) bacilli inhibited from acquiring iron from the host are severely attenuated. In contrast, increased dietary iron concentrations or patients with hemochromatosis have long been associated with a more severe tuberculosis (...) (TB) disease outcome. We have observed that upon macrophage infection, Mtb bacilli strongly promote intracellular iron sequestration, both through increased expression of hepcidin, a key mammalian iron regulatory protein, and downregulation of the iron exporter protein, ferroportin. Heparin is a highly sulfated glycosaminoglycan released by mast cells and basophils at sites of tissue injury. During Mtb infection, heparin alters intracellular trafficking in alveolar epithelial cells and decreases

2018 Scientific reports

15. Immunity against the Obligate Intracellular Bacterial Pathogen Rickettsia australis Requires a Functional Complement System Full Text available with Trip Pro

Immunity against the Obligate Intracellular Bacterial Pathogen Rickettsia australis Requires a Functional Complement System The complement system has a well-defined role in deterring blood-borne infections. However, complement is not entirely efficacious, as several bacterial pathogens, including some obligate intracellular pathogens, have evolved mechanisms for resistance. It is presumed that obligate intracellular bacteria evade complement attack by residing within a host cell; however (...) , recent studies have challenged this presumption. Here, we demonstrate that the complement system is activated during infection with the obligate intracellular bacterium Rickettsia australis and that genetic ablation of complement increases susceptibility to infection. Interaction of Rickettsia australis with serum-borne complement leads to activation of the complement cascade, producing three effector mechanisms that could negatively influence R. australis. The C9-dependent membrane attack complex

2018 Infection and immunity

16. Overexpression of Cu-Zn SOD in Brucella abortus suppresses bacterial intracellular replication via down-regulation of Sar1 activity Full Text available with Trip Pro

Overexpression of Cu-Zn SOD in Brucella abortus suppresses bacterial intracellular replication via down-regulation of Sar1 activity Brucella Cu-Zn superoxide dismutase (Cu-Zn SOD) is a periplasmic protein, and immunization of mice with recombinant Cu-Zn SOD protein confers protection against Brucella abortus infection. However, the role of Cu-Zn SOD during the process of Brucella infection remains unknown. Here, we report that Cu-Zn SOD is secreted into culture medium and is translocated (...) into host cells independent of type IV secretion systems (T4SS). Furthermore, co-immunoprecipitation and immunofluorescence studies reveal that Brucella abortus Cu-Zn SOD interacts with the small GTPase Sar1. Overexpression of Cu-Zn SOD in Brucella abortus inhibits bacterial intracellular growth by abolishing Sar1 activity in a manner independent of reactive oxygen species (ROS) production.

2018 Oncotarget

17. The Immunoregulation of Th17 in Host against Intracellular Bacterial Infection Full Text available with Trip Pro

of pathogens, including bacteria and viruses. The underlying mechanisms by which Th17 performs include dendritic cell (DC) regulation, neutrophil recruitment, Th1 modulation, and T regulatory cell (Treg) balance. In recent years, researchers have generated an accumulating wealth of evidence on the role of Th17/IL17 in protective immunity to intracellular bacterial pathogens, such as Mycobacterium tuberculosis and Chlamydia trachomatis, which are one of the most important pathogens that inflict significant (...) The Immunoregulation of Th17 in Host against Intracellular Bacterial Infection T helper 17 cells (Th17) constitute a distinct subset of helper T cells with a unique transcriptional profile (STAT3, RORγ, and RORα), cytokine production pattern (IL17 family), and requirement of specific cytokines for their differentiation (TGF-β, IL6, IL21, and IL23). Recent studies involving experimental animals and humans have shown that Th17/IL17 plays a crucial role in host defense against a variety

2018 Mediators of inflammation

18. The Binary Toxin CDT of Clostridium difficile as a Tool for Intracellular Delivery of Bacterial Glucosyltransferase Domains Full Text available with Trip Pro

The Binary Toxin CDT of Clostridium difficile as a Tool for Intracellular Delivery of Bacterial Glucosyltransferase Domains Binary toxins are produced by several pathogenic bacteria. Examples are the C2 toxin from Clostridium botulinum, the iota toxin from Clostridium perfringens, and the CDT from Clostridium difficile. All these binary toxins have ADP-ribosyltransferases (ADPRT) as their enzymatically active component that modify monomeric actin in their target cells. The binary C2 toxin (...) uptake was demonstrated by the analysis of cell morphology, cytoskeleton staining, and intracellular substrate glucosylation. The fusion toxins were functional only when the adapter domain of CDTa was N-terminally located, according to its native orientation. Thus, like other binary toxins, the CDTaN/b system can be used for standardized delivery systems not only for bacterial ADPRTs but also for a variety of bacterial glucosyltransferase domains.

2018 Toxins

19. A cell-based infection assay identifies efflux pump modulators that reduce bacterial intracellular load Full Text available with Trip Pro

A cell-based infection assay identifies efflux pump modulators that reduce bacterial intracellular load Bacterial efflux pumps transport small molecules from the cytoplasm or periplasm outside the cell. Efflux pump activity is typically increased in multi-drug resistant (MDR) pathogens; chemicals that inhibit efflux pumps may have potential for antibiotic development. Using an in-cell screen, we identified three efflux pump modulators (EPMs) from a drug diversity library. The screening platform (...) uses macrophages infected with the human Gram-negative pathogen Salmonella enterica (Salmonella) to identify small molecules that prevent bacterial replication or survival within the host environment. A secondary screen for hit compounds that increase the accumulation of an efflux pump substrate, Hoechst 33342, identified three small molecules with activity comparable to the known efflux pump inhibitor PAβN (Phe-Arg β-naphthylamide). The three putative EPMs demonstrated significant antibacterial

2018 PLoS pathogens

20. Autophagy and Its Interaction With Intracellular Bacterial Pathogens Full Text available with Trip Pro

Autophagy and Its Interaction With Intracellular Bacterial Pathogens Cellular responses to stress can be defined by the overwhelming number of changes that cells go through upon contact with and stressful conditions such as infection and modifications in nutritional status. One of the main cellular responses to stress is autophagy. Much progress has been made in the understanding of the mechanisms involved in the induction of autophagy during infection by intracellular bacteria. This review (...) aims to discuss recent findings on the role of autophagy as a cellular response to intracellular bacterial pathogens such as, Streptococcus pyogenes, Mycobacterium tuberculosis, Shigella flexneri, Salmonella typhimurium, Listeria monocytogenes, and Legionella pneumophila, how the autophagic machinery senses these bacteria directly or indirectly (through the detection of bacteria-induced nutritional stress), and how some of these bacterial pathogens manage to escape from autophagy.

2018 Frontiers in immunology

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