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Virulence variation of Mycobacterium avium in myeloid cells

Cancade, Sacha (2023) MOBN03 20222
Degree Projects in Molecular Biology
Popular Abstract
A better understanding of Mycobacterium avium for a better treatment?

Nontuberculous mycobacteria (NTM) are common bacteria found in water and soil. They are opportunistic pathogens of humans and animals. Among them, a group called Mycobacterium avium complex (MAC) is a major cause of pulmonary diseases. These infections are very hard to treat and have high mortality rates. Mycobacterium avium is the most prevalent NTM species found in patient samples in Europe. M. avium diseases are on the rise, not only in individuals with weakened immune systems but also in immunocompetent peoples with chronic pulmonary conditions. Those conditions cause them to have inflammation caused by a type of immune cell, the neutrophils. It is difficult to... (More)
A better understanding of Mycobacterium avium for a better treatment?

Nontuberculous mycobacteria (NTM) are common bacteria found in water and soil. They are opportunistic pathogens of humans and animals. Among them, a group called Mycobacterium avium complex (MAC) is a major cause of pulmonary diseases. These infections are very hard to treat and have high mortality rates. Mycobacterium avium is the most prevalent NTM species found in patient samples in Europe. M. avium diseases are on the rise, not only in individuals with weakened immune systems but also in immunocompetent peoples with chronic pulmonary conditions. Those conditions cause them to have inflammation caused by a type of immune cell, the neutrophils. It is difficult to treat these infections because M. avium is naturally resistant to many antibiotics. The available treatments are long and toxic. Additionally, precisely diagnosing M. avium infections is complex, and we need more reliable diagnostic methods.
M. avium mainly targets macrophages, which are key immune cells. These bacteria have developed strategies to invade and multiply within macrophages. They can also infect neutrophils. Neutrophils help control the infection in early stages, but they seem to be detrimental as the disease progresses.
We need a better understanding of the interactions between M. avium and host cells in order to develop improved treatments, diagnostic techniques, and preventive measures.

Within a population of bacteria, distinct forms can emerge, visually distinguishable by their appearances. M. avium has two main appearances. First, the smooth transparent form (SmT), very efficient at infecting cells, more common among patients and capable of multiplying within macrophages. This form displays higher antibiotic resistance and has mechanisms to avoid elimination by host. Secondly, the smooth opaque form (SmO), less capable of causing infections in macrophages and more easily eliminated. The bacteria can switch back and forth between those two appearances. It could be that SmO is a form more adapted to life in the environment. When entering the organism, interactions with the host could induced its conversion into SmT, the form more capable at infecting.
However, we are uncertain about the exact factors controlling this switch, but we supposed that they depend on the type of cells that are infected. Comprehension of the mechanisms behind this switch is important to explain M. avium’s ability to cause disease and thus develop strategies to combat the infection.

The aim of this project was to study a new strain, LU439, and to investigate the changes that occur in M. avium when it infects macrophages compare to neutrophils. We wanted to identify the factors and conditions in the host that trigger the changes in these bacteria and understand the molecular mechanisms involved. By exploring these processes, we hope to contribute to the development of more effective strategies for managing M. avium infections. Indeed, finding a way to prevent M. avium from switching to the form causing disease may be used to stop infections in susceptible individuals. while inducing a switch toward the harmless form of the bacteria could be used to treat infected patients since it would be more easily eliminated by the host and responds better to antibiotics.

We characterized this strain LU439 by conducting various experiments. The results shown strong characteristics corresponding to previous descriptions of M. avium found in literature. Thus, the LU439 strain appears to be a valuable model system for further experimentation.

In neutrophils, SmO form appear to be capable of persisting within the cells and even grow, while SmT form display a bigger growth than during macrophages infection. This difference in bacterial growth may be due to the early cell death of neutrophils, indicating their limited ability to control the infection.
Thus, we are investigating on the possibility that interaction with neutrophils could favorized a switch toward SmT, the more infective form.

These findings could be used to clarify the complex interactions between bacteria and host cells, and thus, contribute to a better understanding of the mechanisms underlying M. avium infections and to a better clinical management of this disease.

Molecular Biology Master’s Thesis (60hp)
Main Supervisor: Julia Lienard (Lund University)
Co-Supervisor: Katie Laschanzky (Lund University) (Less)
Please use this url to cite or link to this publication:
author
Cancade, Sacha
supervisor
organization
course
MOBN03 20222
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9140656
date added to LUP
2023-10-31 11:09:07
date last changed
2023-10-31 11:09:07
@misc{9140656,
  author       = {{Cancade, Sacha}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Virulence variation of Mycobacterium avium in myeloid cells}},
  year         = {{2023}},
}