About this Research Topic
Tuberculosis is one of the serious global public health problems. According to the statistics of the World Health Organization, there are about 10 million people suffering from tuberculosis and 1.5 million deaths in 2020. With the increasing emphasis on TB prevention and treatment in various countries, the number of annual TB deaths worldwide decreased by 45% between 2000 and 2019. However, due to the emergence of the COVID-19 epidemic and the shortage of medical resources, the number of newly diagnosed TB cases worldwide has decreased significantly, from 7.1 million in 2019 to 5.8 million in 2020, far lower than the total of 10 million in 2020. The decline in the prevalence of TB tends to be flat, which also proves that the treatment of TB is becoming more difficult. Therefore, tuberculosis is still one of the deadliest infectious diseases in the world. With the emergence of drug-resistant strains, the global mobility of population and the epidemic of AIDS, the treatment and control of tuberculosis is becoming more and more difficult.
Mycobacterium tuberculosis, the bacterium causing TB, is an intracellular pathogen, which can enter a persistent state after being taken up by macrophages. Persisters are one of the main reasons for the long-term drug therapy, relapse and drug resistance of TB, and also one of the reasons for the difficulty in TB control. A persister is different from a drug resistant mutant of M. tuberculosis; it does not grow in the presence of a lethal concentration of antibiotics, it belongs to the drug-tolerant cell subgroup, and its resistance to antibiotics cannot be inherited. Persisters are genetically identical to the rest of the bacterial population, but they are dormant, which protects them from killing by antibiotics. When re-cultured and restored to growth, all kinds of physiological activities and the drug sensitivity of the persister are not different from those of the original strain. To establish dormancy, the bacterium must evade the immune system. Once conditions are favourable, for example under conditions of immune suppression, the pathogen reactivates, exiting its dormant state and causing disease.
In this Research topic, we will focus on factors affecting the drug resistance and virulence of M. tuberculosis, and factors affecting dormancy, immune evasion and pathogen persistence in the host. The research topic includes but is not limited to:
• The identification and characterization of drug resistance- and tolerance-related factors and virulence factors, including studies of their structure and function.
• The interaction between host and pathogen, including evasion of the immune system to enter dormancy, granuloma formation and factors affecting reactivation of latent disease.
• Novel therapies targeting persisters or host molecules involved in persistence
• Biomarkers of latent and active disease
Mycobacterium tuberculosis, the bacterium causing TB, is an intracellular pathogen, which can enter a persistent state after being taken up by macrophages. Persisters are one of the main reasons for the long-term drug therapy, relapse and drug resistance of TB, and also one of the reasons for the difficulty in TB control. A persister is different from a drug resistant mutant of M. tuberculosis; it does not grow in the presence of a lethal concentration of antibiotics, it belongs to the drug-tolerant cell subgroup, and its resistance to antibiotics cannot be inherited. Persisters are genetically identical to the rest of the bacterial population, but they are dormant, which protects them from killing by antibiotics. When re-cultured and restored to growth, all kinds of physiological activities and the drug sensitivity of the persister are not different from those of the original strain. To establish dormancy, the bacterium must evade the immune system. Once conditions are favourable, for example under conditions of immune suppression, the pathogen reactivates, exiting its dormant state and causing disease.
In this Research topic, we will focus on factors affecting the drug resistance and virulence of M. tuberculosis, and factors affecting dormancy, immune evasion and pathogen persistence in the host. The research topic includes but is not limited to:
• The identification and characterization of drug resistance- and tolerance-related factors and virulence factors, including studies of their structure and function.
• The interaction between host and pathogen, including evasion of the immune system to enter dormancy, granuloma formation and factors affecting reactivation of latent disease.
• Novel therapies targeting persisters or host molecules involved in persistence
• Biomarkers of latent and active disease
Keywords: Mycobacterium tuberculosis, drug resistance, virulence, persister, immunity
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