scholarly journals Time-Resolved Proteome Analysis of Listeria monocytogenes during Infection Reveals the Role of the AAA+ Chaperone ClpC for Host Cell Adaptation

mSystems ◽  
2021 ◽  
Author(s):  
Marlène S. Birk ◽  
Rina Ahmed-Begrich ◽  
Stefan Tran ◽  
Alexander K. W. Elsholz ◽  
Christian K. Frese ◽  
...  

Survival and proliferation of pathogenic bacteria inside the host depend on their ability to adapt to the changing environment. Profiling the underlying changes on the bacterial proteome level during the infection process is important to gain a better understanding of the pathogenesis and the host-dependent adaptation processes.

Author(s):  
Ann-Kathrin Mix ◽  
Griseldis Goob ◽  
Erik Sontowski ◽  
Christof R. Hauck

AbstractPathogenic bacteria have evolved a variety of highly selective adhesins allowing these microbes to engage specific surface determinants of their eukaryotic host cells. Receptor clustering induced by the multivalent microorganisms will not only anchor the bacteria to the tissue, but will inevitably trigger host cell signaling. It has become clear, that these bacteria-initiated signaling events can be seen as a form of localized communication with host epithelial cells. Such a microscale communication can have immediate consequences in the form of changes in host cell membrane morphology or cytoskeletal organization, but can also lead to transcriptional responses and medium- and long-term alterations in cellular physiology. In this review, we will discuss several examples of this form of microscale communication between bacterial pathogens and mammalian host cells and try to delineate their downstream ramifications in the infection process. Furthermore, we will highlight recent findings that specialized pathogenic bacteria utilize the adhesin-based interaction to diffuse the short-range messenger molecule nitric oxide into the host tissue. While anti-adhesive strategies to disrupt the initial bacterial attachment have not yet translated into medical applications, the ability to interfere with the microscale communication emanating on the host side provides an unconventional approach for preventing infectious diseases.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Gokhlesh Kumar ◽  
Karin Hummel ◽  
Katharina Noebauer ◽  
Timothy J. Welch ◽  
Ebrahim Razzazi-Fazeli ◽  
...  

2021 ◽  
Vol 17 (8) ◽  
pp. e1009837
Author(s):  
Yi Gong ◽  
Xiaoyuan Wei ◽  
Wanwei Sun ◽  
Xin Ren ◽  
Jiao Chen ◽  
...  

It is well known that exosomes could serve as anti-microbial immune factors in animals. However, despite growing evidences have shown that the homeostasis of the hemolymph microbiota was vital for immune regulation in crustaceans, the relationship between exosomes and hemolymph microbiota homeostasis during pathogenic bacteria infection has not been addressed. Here, we reported that exosomes released from Vibrio parahaemolyticus-infected mud crabs (Scylla paramamosain) could help to maintain the homeostasis of hemolymph microbiota and have a protective effect on the mortality of the host during the infection process. We further confirmed that miR-224 was densely packaged in these exosomes, resulting in the suppression of HSP70 and disruption of the HSP70-TRAF6 complex, then the released TRAF6 further interacted with Ecsit to regulate the production of mitochondrial ROS (mROS) and the expression of Anti-lipopolysaccharide factors (ALFs) in recipient hemocytes, which eventually affected hemolymph microbiota homeostasis in response to the pathogenic bacteria infection in mud crab. To the best of our knowledge, this is the first document that reports the role of exosome in the hemolymph microbiota homeostasis modulation during pathogen infection, which reveals the crosstalk between exosomal miRNAs and innate immune response in crustaceans.


Toxins ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 38 ◽  
Author(s):  
Brittney N. Nguyen ◽  
Daniel A. Portnoy

Listeriolysin O (LLO) is a pore-forming cytolysin that allows Listeria monocytogenes to escape from phagocytic vacuoles and enter the host cell cytosol. LLO is expressed continuously during infection, but it has been a challenge to evaluate the importance of LLO secreted in the host cell cytosol because deletion of the gene encoding LLO (hly) prevents localization of L. monocytogenes to the cytosol. Here, we describe a L. monocytogenes strain (hlyfl) in which hly is flanked by loxP sites and Cre recombinase is under the transcriptional control of the L. monocytogenes actA promoter, which is highly induced in the host cell cytosol. In less than 2 h after infection of bone marrow-derived macrophages (BMMs), bacteria were 100% non-hemolytic. hlyfl grew intracellularly to levels 10-fold greater than wildtype L. monocytogenes and was less cytotoxic. In an intravenous mouse model, 90% of bacteria were non-hemolytic within three hours in the spleen and eight hours in the liver. The loss of LLO led to a 2-log virulence defect in the spleen and a 4-log virulence defect in the liver compared to WT L. monocytogenes. Thus, the production of LLO in the cytosol has significant impact on the pathogenicity of L. monocytogenes.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Gokhlesh Kumar ◽  
Karin Hummel ◽  
Katharina Noebauer ◽  
Timothy J. Welch ◽  
Ebrahim Razzazi-Fazeli ◽  
...  

Author(s):  
Pramod Dhakal ◽  
Ankit a Achary ◽  
Vedamurthy Joshi

Bioenhancers are drug facilitator which do not show the typical drug activity but in combination to enhance the activity of other molecule in several way including increase the bioavailability of drug across the membrane, potentiating the drug molecules by conformational interaction, acting as receptor for drug molecules and making target cell more receptive to drugs and promote and increase the bioactivity or bioavailability or the uptake of drugs in combination therapy. The objective of the present study was to evaluate the antibacterial and activity of combination in Azadirachta indica extract with cow urine distillate and pepper extract against common pathogenic bacteria, a causative agent of watery diarrhea. It has been found that Indian indigenous cow urine and its distillate also possess bioenhancing ability. Bioenhancing role of cow urine distillate (CUD) and pepper extract was investigated on antibacterial activity of ethanol extract of Azadirachta indica. Antibacterial activity of ethanol extract neem alone and in combination with CUD and pepper extract were determined the ATCC strains against Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and E-coli by cup plate diffusion method. Ethanol extract of neem has showed more effect on P. aeruginosa, E-coli than S. aureus and K. pneumonia with combination of CUD and pepper extract. CUD and pepper did not show any inhibition of test bacteria in low concentration. The antibacterial effect of combination of extract and CUD was higher than the inhibition caused by extract alone and is suggestive of the bioenhancing role of cow urine distillate and pepper. Moreover, inhibition of test bacteria was observed with less concentration of extract on combining with CUD


2020 ◽  
Vol 27 ◽  
Author(s):  
Ramarao Malla ◽  
Mohammad Amjad Kamal

: Cervical cancer (CC) is the fourth leading cancer in women in the age group 15-44 globally. Experimental as well as epidemiological studies identified that type16 and 18 HPV cause 70% of precancerous cervical lesions as well as cervical cancer worldwide by bringing about genetic as well as epigenetic changes in the host genome. The insertion of the HPV genome triggers various defense mechanisms including the silencing of tumor suppressor genes as well as activation of oncogenes associated with cancer metastatic pathway. E6 and E7 are small oncoproteins consisting of 150 and 100 amino acids respectively. These oncoproteins affect the regulation of the host cell cycle by interfering with p53 and pRb. Further these oncoproteins adversely affect the normal functions of the host cell by binding to their signaling proteins. Recent studies demonstrated that E6 and E7 oncoproteins are potential targets for CC. Therefore, this review discusses the role of E6 and E7 oncoproteins in metastasis and drug resistance as well as their regulation, early oncogene mediated signaling pathways. This review also uncovers the recent updates on molecular mechanisms of E6 and E7 mediated phytotherapy, gene therapy, immune therapy, and vaccine strategies as well as diagnosis through precision testing. Therefore, understanding the potential role of E6/E7 in metastasis and drug resistance along with targeted treatment, vaccine, and precision diagnostic strategies could be useful for the prevention and treatment of cervical cancer.


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