scholarly journals Role of caveolae in Leishmania chagasi phagocytosis and intracellular survival in macrophages

2006 ◽  
Vol 8 (7) ◽  
pp. 1106-1120 ◽  
Author(s):  
Nilda E. Rodriguez ◽  
Upasna Gaur ◽  
Mary E. Wilson
Keyword(s):  
Intracellular Survival ◽  
Leishmania Chagasi

An AraC/XylS Family Transcriptional Regulator Modulates the Oxidative Stress Response of Francisella tularensis

2021 ◽  
Author(s):  
Dina Marghani ◽  
Zhuo Ma ◽  
Anthony J. Centone ◽  
Weihua Huang ◽  
Meenakshi Malik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Francisella Tularensis ◽  
Human Disease ◽  
Transcriptional Regulator ◽  
Intracellular Survival ◽  
Gram Negative ◽  
Expression Of Genes ◽  
Transcription Regulators

Francisella tularensis is a Gram-negative bacterium that causes a fatal human disease known as tularemia. The Centers for Disease Control have classified F. tularensis as Category A Tier-1 Select Agent. The virulence mechanisms of Francisella are not entirely understood. Francisella possesses very few transcription regulators, and most of these regulate the expression of genes involved in intracellular survival and virulence. The F. tularensis genome sequence analysis reveals an AraC ( FTL_ 0689) transcriptional regulator homologous to the AraC/XylS family of transcriptional regulators. In Gram-negative bacteria, AraC activates genes required for L-arabinose utilization and catabolism. The role of the FTL_ 0689 regulator in F. tularensis is not known. In this study, we characterized the role of FTL_ 0689 in gene regulation of F. tularensis and investigated its contribution to intracellular survival and virulence. The results demonstrate that FTL_0689 in Francisella is not required for L-arabinose utilization. Instead, FTL_ 0689 specifically regulates the expression of the oxidative and global stress response, virulence, metabolism, and other key pathways genes required by Francisella when exposed to oxidative stress. The FTL_0689 mutant is attenuated for intramacrophage growth and virulence in mice. Based on the deletion mutant phenotype, FTL_0689 was termed osrR ( o xidative s tress r esponse r egulator). Altogether, this study elucidates the role of the osrR transcriptional regulator in tularemia pathogenesis. IMPORTANCE: The virulence mechanisms of category A select agent Francisella tularensis , the causative agent of a fatal human disease known as tularemia, remain largely undefined. The present study investigated the role of a transcriptional regulator and its overall contribution to the oxidative stress resistance of F. tularensis . The results provide an insight into a novel gene regulatory mechanism, especially when Francisella is exposed to oxidative stress conditions. Understanding such Francisella - specific regulatory mechanisms will identify potential targets for developing effective therapies and vaccines to prevent tularemia.

Rv2223c, an acid inducible carboxyl-esterase of Mycobacterium tuberculosis enhanced the growth and survival of Mycobacterium smegmatis

2019 ◽  
Vol 14 (16) ◽  
pp. 1397-1415
Author(s):  
Pratibha Maan ◽  
Jagdeep Kaur
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Intracellular Survival ◽  
Growth And Survival ◽  
Enhanced Expression ◽  
Stress Environment ◽  
In Vitro Stress ◽  
Carboxyl Esterase

Aim: To elucidate the role of Rv2223c in Mycobacterium tuberculosis. Methods: Purified recombinant Rv2223c protein was characterized. Expression of rv2223c in the presence of different stress environment and subcellular localization were performed in M. tuberculosis H37Ra and Mycobacterium smegmatis ( MS_2223c). Effect of its overexpression on growth rate, infection and intracellular survival in THP-1/PBMC cells were studied. Results: rRv2223c demonstrated esterase activity with preference for pNP-octanoate and hydrolyzed trioctanoate to di- and mono-octanoate. Expression of rv2223c was upregulated in acidic and nutritive stress conditions. rRv2223c was identified in extracellular and cell wall fractions. MS_2223c exhibited enhanced growth, survival during in vitro stress, infection and intracellular survival. Conclusions: Rv2223c is a secretary, carboxyl-esterase, with enhanced expression under acidic and nutritive stress condition and might help in intracellular survival of bacteria.

scholarly journals Regulation of Cell Growth during Serum Starvation and Bacterial Survival in Macrophages by the Bifunctional Enzyme SpoT in Helicobacter pylori

2008 ◽  
Vol 190 (24) ◽  
pp. 8025-8032 ◽  
Author(s):  
Yan Ning Zhou ◽  
William G. Coleman ◽  
Zhaoxu Yang ◽  
Yi Yang ◽  
Nathaniel Hodgson ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Cell Growth ◽  
Intracellular Survival ◽  
Hydrolase Activity ◽  
Serum Starvation ◽  
Bifunctional Enzyme ◽  
Synthetase Activity ◽  
Bacterial Survival ◽  
H Pylori

ABSTRACT In Helicobacter pylori the stringent response is mediated solely by spoT. The spoT gene is known to encode (p)ppGpp synthetase activity and is required for H. pylori survival in the stationary phase. However, neither the hydrolase activity of the H. pylori SpoT protein nor the role of SpoT in the regulation of growth during serum starvation and intracellular survival of H. pylori in macrophages has been determined. In this study, we examined the effects of SpoT on these factors. Our results showed that the H. pylori spoT gene encodes a bifunctional enzyme with both a hydrolase activity and the previously described (p)ppGpp synthetase activity, as determined by introducing the gene into Escherichia coli relA and spoT defective strains. Also, we found that SpoT mediates a serum starvation response, which not only restricts the growth but also maintains the helical morphology of H. pylori. Strikingly, a spoT null mutant was able to grow to a higher density in serum-free medium than the wild-type strain, mimicking the “relaxed” growth phenotype of an E. coli relA mutant during amino acid starvation. Finally, SpoT was found to be important for intracellular survival in macrophages during phagocytosis. The unique role of (p)ppGpp in cell growth during serum starvation, in the stress response, and in the persistence of H. pylori is discussed.

scholarly journals Intracellular Survival of Leishmania major in Neutrophil Granulocytes after Uptake in the Absence of Heat-Labile Serum Factors

2002 ◽  
Vol 70 (2) ◽  
pp. 826-835 ◽  
Author(s):  
Helmut Laufs ◽  
Kerstin Müller ◽  
Jens Fleischer ◽  
Norbert Reiling ◽  
Nicole Jahnke ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Intracellular Survival ◽  
Host Cells ◽  
Polymorphonuclear Neutrophil ◽  
Heat Inactivation ◽  
Neutrophil Granulocytes ◽  
Complement Components ◽  
Serum Factors

ABSTRACT The role of polymorphonuclear neutrophil granulocytes (PMN) in defense against the intracellular parasite Leishmania is poorly understood. In the present study, the interaction of human PMN with Leishmania major promastigotes was investigated in vitro. In the presence of fresh human serum, about 50% of PMN phagocytosed the parasites within 10 min and the parasite uptake led to PMN activation, resulting in the killing of most ingested parasites. Heat inactivation of the serum markedly reduced the rate of early parasite phagocytosis, suggesting a role of complement components in the early uptake of Leishmania. However, over 50% of PMN were able to ingest parasites in the presence of heat-inactivated serum if the coincubation was extended to 3 h. After 3 h, 10% of the PMN were found to internalize Leishmania even under serum-free conditions. These findings indicate that PMN possess mechanisms for both opsonin/complement-dependent and -independent uptake of Leishmania. Both pathways of uptake could be partially blocked by anti-CR3 antibody. Mannan-binding lectin was found not to be involved in this process. When phagocytosed in the absence of opsonin, the majority of Leishmania parasites survived intracellularly in PMN for at least 1 day. These data suggest a dual role of PMN in the early response to L. major infection. On the one hand, PMN can rapidly eliminate the intracellular parasites, and on the other hand, Leishmania can survive intracellularly in PMN. These data, together with the finding that intact parasites were seen in PMN isolated from the skin of infected mice, suggest that PMN can serve as host cells for the intracellular survival of Leishmania within the first hours or days after infection.

scholarly journals The Involvement of Mycobacterium Type III-A CRISPR-Cas System in Oxidative Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Fan Yang ◽  
Lingqing Xu ◽  
Lujie Liang ◽  
Wanfei Liang ◽  
Jiachen Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Envelope ◽  
Reduction Process ◽  
Intracellular Survival ◽  
Host Immunity ◽  
Type I ◽  
Type Iii

Type I and type II CRISPR-Cas systems are employed to evade host immunity by targeting interference of bacteria’s own genes. Although Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, possesses integrated type III-A CRISPR-Cas system, its role in mycobacteria remains obscure. Here, we observed that seven cas genes (csm2∼5, cas10, cas6) were upregulated in Mycobacterium bovis BCG under oxidative stress treatment, indicating the role of type III-A CRISPR-Cas system in oxidative stress. To explore the functional role of type III-A CRISPR-Cas system, TCC (Type III-A CRISPR-Cas system, including cas6, cas10, and csm2-6) mutant was generated. Deletion of TCC results in increased sensitivity in response to hydrogen peroxide and reduced cell envelope integrity. Analysis of RNA-seq dataset revealed that TCC impacted on the oxidation-reduction process and the composition of cell wall which is essential for mycobacterial envelop integrity. Moreover, disrupting TCC led to poor intracellular survival in vivo and in vitro. Finally, we showed for the first time that TCC contributed to the regulation of regulatory T cell population, supporting a role of TCC in modulating host immunity. Our finding reveals the important role of TCC in cell envelop homeostasis. Our work also highlights type III-A CRISPR-Cas system as an important factor for intracellular survival and host immunoregulation in mycobacteria, thus may be a potential target for therapy.

The role of TREM-2 in internalization and intracellular survival of Brucella abortus in murine macrophages

2015 ◽  
Vol 163 (3-4) ◽  
pp. 194-201 ◽  
Author(s):  
Pan Wei ◽  
Qiang Lu ◽  
Guimei Cui ◽  
Zhenhong Guan ◽  
Li Yang ◽  
...  
Keyword(s):  
Brucella Abortus ◽  
Intracellular Survival ◽  
Murine Macrophages

scholarly journals The role of autophagy in the intracellular survival ofCampylobacter concisus

FEBS Open Bio ◽  
2014 ◽  
Vol 4 (1) ◽  
pp. 301-309 ◽  
Author(s):  
Jose A. Burgos-Portugal ◽  
Hazel M. Mitchell ◽  
Natalia Castaño-Rodríguez ◽  
Nadeem O. Kaakoush
Keyword(s):  
Intracellular Survival

scholarly journals Role of the 85-Kilobase Plasmid and Plasmid-Encoded Virulence-Associated Protein A in Intracellular Survival and Virulence of Rhodococcus equi

1999 ◽  
Vol 67 (7) ◽  
pp. 3548-3557 ◽  
Author(s):  
Steeve Giguère ◽  
Mary K. Hondalus ◽  
Julie A. Yager ◽  
Patricia Darrah ◽  
David M. Mosser ◽  
...  
Keyword(s):  
Clinical Isolate ◽  
Protein A ◽  
Intracellular Survival ◽  
Rhodococcus Equi ◽  
Mouse Macrophages ◽  
Young Horses ◽  
Native Host ◽  
Derivatives Of

ABSTRACT Rhodococcus equi is a facultative intracellular pathogen of macrophages and a cause of pneumonia in young horses (foals) and immunocompromised people. Isolates of R. equi from pneumonic foals typically contain large, 85- or 90-kb plasmids encoding a highly immunogenic virulence-associated protein (VapA). The objective of this study was to determine the role of the 85-kb plasmid and VapA in the intracellular survival and virulence of R. equi. Clinical isolates containing the plasmid and expressing VapA efficiently replicated within mouse macrophages in vitro, while plasmid-cured derivatives of these organisms did not multiply intracellularly. An isolate harboring the large plasmid also replicated in the tissues of experimentally infected mice, whereas its plasmid-cured derivative was rapidly cleared. All foals experimentally infected with a plasmid-containing clinical isolate developed severe bronchopneumonia, whereas the foals infected with its plasmid-cured derivative remained asymptomatic and free of visible lung lesions. By day 14 postinfection, lung bacterial burdens had increased considerably in foals challenged with the plasmid-containing clinical isolate. In contrast, bacteria could no longer be cultured from the lungs of foals challenged with the isogenic plasmid-cured derivative. A recombinant, plasmid-cured derivative expressing wild-type levels of VapA failed to replicate in macrophages and remained avirulent for both mice and foals. These results show that the 85-kb plasmid of R. equi is essential for intracellular replication within macrophages and for development of disease in the native host, the foal. However, expression of VapA alone is not sufficient to restore the virulence phenotype.

scholarly journals Exploring the Possible Role of Nature in Curing Leishmaniasis

2019 ◽  
pp. 1-21
Author(s):  
Ravinder Sharma ◽  
Vikas Gupta ◽  
Viney Chawla ◽  
Pooja Chawla
Keyword(s):  
Natural Products ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Chemotherapeutic Agents ◽  
Leishmania Braziliensis ◽  
Leishmania Chagasi ◽  
Major Health Problem ◽  
Major Health ◽  
Number Of Plant Species

Background: Communicable diseases have always been a threat to mankind since times immemorial. Leishmaniasis, an infectious disease caused by protozoan of various species of leishmania, is a major health problem spreading across 98 countries and about 350 million people stand the risk of this infection worldwide. Medical research has struggled a lot to combat this disease. Objective: Among the various approaches available for treatment of Leishmaniasis, many are costly so there is a need to develop effective but economical and easily available antileishmanial agents. Methods: Natural products are important source of various new medicaments and their derivatives can be used for synthetic modification and bioactivity optimization. Therefore, in order to fulfil the need for novel, economical, more effective and safer chemotherapeutic agents, scientists have explored Mother Nature in detail. Results: A number of plant species possess inhibitory activity against certain types of parasites such as Leishmania major, Leishmania amazonensis, Leishmania aethiopica, Leishmania braziliensis, Leishmania mexicana, Leishmania infantum, Leishmania chagasi and Leishmania donovani. Moreover natural products are economical, safer, more effective and without considerable side effects. Conclusion: The present review highlights the leishmanicidal activity of various natural products with an insight in to their possible mechanism.

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