Mycobacterium Tuberculosis Virulence: Insights and Impact on Vaccine Development

Abstract

The existing TB vaccine, the attenuated Mycobacterium bovis strain BCG, is effective in protecting infants from severe forms of the disease, while its efficacy in protecting adults from pulmonary TB is poor. In the last two decades, a renewed interest in TB resulted in the development of several candidate vaccines that are now entering clinical trials. However, most of these vaccines are based on a common rationale and aim to induce a strong T-cell response against Mycobacterium tuberculosis. Recent advancements in the understanding of M. tuberculosis virulence determinants and associated pathogenic strategies are opening a new and broader view of the complex interaction between this remarkable pathogen and the human host, providing insights at molecular level that could lead to a new rationale for the design of novel antitubercular vaccines. A vaccination strategy that simultaneously targets different steps in TB pathogenesis may result in improved protection and reduced TB transmission.

Differential determinants of virulence in twoMycobacterium tuberculosisColombian clinical isolates of the LAM09 family

“…In vitro culture of Mtb under conditions restricting survival and/or proliferation such as hypoxia, acidic pH, and nutrient deprivation, among others, which happen during macrophage infection, has been used to find critical genes associated to virulence and pathogenicity [71,72]. A carbon-restricted medium such as Sauton's has been used to simulate particular stress conditions found by Mtb during its residency in phagocytic cells or inside the granuloma.…”

Bacterial Virulence Factors: Secreted for Survival

“…Various ligands present on the mycobacterial cell surface such as phosphatidylinositol mannoside (PIM), HSP70, 19 kDa lipoprotein, lipoarabinomannan (LAM) are recognised by phagocytic receptors and/or specific pattern recognition receptors (PRRs) present at the cell membrane of macrophages or DCs [3]. Uptake through some of the receptors is thought to be favourable for the pathogen's survival [4]. Within the phagosomes, Mtb generates a complex response and undergoes substantial metabolic shift to adapt in the hostile environment [5].…”

The Alternative Sigma Factors SigE and SigB Are Involved in Tolerance and Persistence to Antitubercular Drugs

“…Moreover, the fact that M. tuberculosis is able to infect and reside in different populations of host cells and the fact that during infection it must face different stressful environmental conditions (8) may account for the coexistence of different subpopu-lations experiencing different physiological states and, consequently, different drug sensitivities.…”