Pathogen | EPFL Graph Search

In biology, a pathogen (πάθος, pathos "suffering", "passion" and -γενής, -genēs "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ. The term pathogen came into use in the 1880s. Typically, the term pathogen is used to describe an infectious microorganism or agent, such as a virus, bacterium, protozoan, prion, viroid, or fungus. Small animals, such as helminths and insects, can also cause or transmit disease. However, these animals are usually referred to as parasites rather than pathogens. The scientific study of microscopic organisms, including microscopic pathogenic organisms, is called microbiology, while parasitology refers to the scientific study of parasites and the organisms that host them. There are several pathways through which pathogens can invade a host. The principal pathways have differen

Functional characterization of the virulence determinant ESX-1 from Mycobacterium tuberculosis

Paloma Julia Soler Arnedo

Tuberculosis (TB) is a chronic infectious disease that mainly affects the lungs and causes extensive human morbidity and mortality. It results from infection with Mycobacterium tuberculosis, a slow-growing intracellular pathogen that can replicate and survive inside macrophages. M. tuberculosis relies on the specialised ESX-1 secretion system to export virulence factors needed for intracellular spread and pathogenesis. The ESX-1 apparatus is a multi-subunit nanomachine composed of ~20 polypeptides including membrane proteins, ATPases, proteases, chaperones and substrates. Although many of the individual components of this secretion system have been characterised, the overall mechanism underlying ESX-1 secretion is still far from clear. To obtain a more comprehensive picture of the functioning of the ESX-1 apparatus, we have studied various components which were largely unexplored in M. tuberculosis. The structural component EccE1, the ESX-1 specific protein EspL and the transcriptional regulator WhiB6 have been investigated in this thesis using an integrative approach involving genetics, biochemistry, proteomics and microscopy. We have demonstrated that EccE1 is a membrane- and cell-wall associated protein critical for secretion of ESX-1 substrates and M. tuberculosis-mediated cell lysis. Deletion of eccE1 from the chromosome severely compromised secretion of EsxA, EsxB, EspA and EspC but not EspB. Localization studies using a florescent-fusion protein showed that EccE1 localises to the poles of M. tuberculosis in the presence of an active ESX-1 system. Our study also shows that EspL is a cytosolic protein needed for stabilising EspE, EspF and EspH, suggesting that it acts as a specific chaperone of the ESX-1 secretion system. Moreover, EspL was shown to interact with EspD and to be important for the secretion of ESX-1 substrates. Lack of EspL resulted in a growth defect ex vivo, loss of cytotoxicity and reduction of innate cytokine production demonstrating its critical role in M. tuberculosis virulence. Analysis of the transcriptional response revealed that the only gene deregulated in the absence of espL was whiB6, encoding a transcriptional factor that positively controls ESX-1 genes. To explore the role of this regulator in M. tuberculosis virulence, we generated a deletion mutant of whiB6 and discovered that its loss resulted in severe reduction of cytotoxicity ex vivo. Overall this investigation improves our current understanding of the ESX-1 secretion system and of the molecular basis of M. tuberculosis virulence. The increased knowledge of the complex interactions between the pathogen and the human host will hopefully translate into new strategies to control the spread of TB.

EPFL2018

Evaluation of pathogens inactivation during thermophilic anaerobic digestion of faecal sludge

Karin Valentine Gallandat López

There is an urgent need to develop comprehensive and sustainable sanitation systems in developing countries, including faecal sludge (FS) treatment technologies that help reduce environmental and human health risks. Anaerobic digestion (AD) is widely used for the treatment of biowastes but its potential for FS sanitization still needs to be assessed. The goal of this work was to evaluate pathogens inactivation during thermophilic AD of a synthetic surrogate for FS through biomethane potential (BMP) tests. Salmonella, Ascaris suum eggs and phages T4 and MS2 were selected as models for bacterial, parasitic and viral pathogens, respectively. Salmonella were not detected anymore after 110 minutes of thermophilic AD. In anaerobic conditions at 55°C, concentrations of phages T4 and MS2 were below detection levels after 3 and 4 days, and no potentially viable Ascaris eggs were found after 15 days. Methods need to be optimized in order to improve the reliability of viability checks on Ascaris eggs. Future experiments could focus on this model, which will a priori be the limiting factor for the dimensioning of anaerobic digesters that yield safe-to-use end products.

2014

The role of immune effectors in controlling Drosophila-microbes interactions

Alice Marra

All live beings are in constant interaction with microorganisms that may be beneficial, deleterious or commensal. Insects in particular live in close contact with microorganisms. This is especially true for species, like the fruit fly Drosophila melanogaster that feed, lay eggs and develop on or close to decomposing organic matter. In contrast to vertebrates, insects did not evolve an adaptive immune system to combat pathogens selectively. They instead rely on surprisingly efficient innate defense mechanisms for the control and clearance of all microbes without any species-specific targeting. Innate immunity encompasses a wide range of mechanisms that rely on direct pathogen recognition and elimination. In addition, metabolic and behavioral responses also strongly affect the outcome of insect interactions with both pathogenic and non-pathogenic bacteria. Although the Drosophila immune system has been extensively described, little is known about the role of immune effectors in tolerating and controlling symbiotic microbes. For this reason, during my PhD studies, I investigated how Drosophila melanogaster immune effectors differentially interact with mutualistic symbionts. First, I investigated the role of some of the host antimicrobials, called antimicrobial peptides and lysozymes, in maintaining the homeostasis of the gut microbiota. I found that both antimicrobial peptides and lysozymes can actively regulate the gut microbiota composition and abundancy, especially during aging. In a second part of my thesis, I got interested in Spiroplasma, a heritable symbiotic bacterium that lives within the fly hemolymph. I characterized the role of the Drosophila iron transporter Transferrin 1 (Tsf1) during Spiroplasma-Drosophila symbiosis. I first showed that mutant flies for tsf1 have an impaired Spiroplasma load, due to iron relocation from the hemolymph to the fat body, where it becomes inaccessible for Spiroplasma. Furthermore, I demonstrated that Spiroplasma scavenges host iron only when it is bound to the protein, which points to Tsf1 and iron transport as a control mechanism for hemolymphatic symbionts. Collectively, my studies contribute to a better understanding of how the innate immune effectors interact with Drosophila microbial symbionts to both regulate and maintain stable, long-lasting, interactions.

EPFL2021