Evolution of Mycobacterium tuberculosis: New Insights into Pathogenicity and Drug Resistance.

The tuberculosis agent Mycobacterium tuberculosis has undergone a long and selective evolution toward human infection and represents one of the most widely spread pathogens due to its efficient aerosol-mediated human-to-human transmission. With the availability of more and more genome sequences, the evolutionary trajectory of this obligate pathogen becomes visible, which provides us with new insights into the molecular events governing evolution of the bacterium and its ability to accumulate drug-resistance mutations. In this review, we summarize recent developments in mycobacterial research related to this matter that are important for a better understanding of the current situation and future trends and developments in the global epidemiology of tuberculosis, as well as for possible public health intervention possibilities.

pks5-recombination-mediated surface remodelling in Mycobacterium tuberculosis emergence.

Mycobacterium tuberculosis is a major, globally spread, aerosol-transmitted human pathogen, thought to have evolved by clonal expansion from a Mycobacterium canettii-like progenitor. In contrast, extant M. canettii strains are rare, genetically diverse, and geographically restricted mycobacteria of only marginal epidemiological importance.

Key experimental evidence of chromosomal DNA transfer among selected tuberculosis-causing mycobacteria.

Horizontal gene transfer (HGT) is a major driving force of bacterial diversification and evolution. For tuberculosis-causing mycobacteria, the impact of HGT in the emergence and distribution of dominant lineages remains a matter of debate. Here, by using fluorescence-assisted mating assays and whole genome sequencing, we present unique experimental evidence of chromosomal DNA transfer between tubercle bacilli of the early-branching Mycobacterium canettii clade.

Revisiting the role of phospholipases C in virulence and the lifecycle of Mycobacterium tuberculosis.

Mycobacterium tuberculosis, the agent of human tuberculosis has developed different virulence mechanisms and virulence-associated tools during its evolution to survive and multiply inside the host. Based on previous reports and by analogy with other bacteria, phospholipases C (PLC) of M. tuberculosis were thought to be among these tools.

A glimpse into the past and predictions for the future: the molecular evolution of the tuberculosis agent.

Recent advances in genomics and molecular biology are providing an excellent opportunity to get a glimpse into the past, to examine the present, and to predict the future evolution of pathogenic mycobacteria, and in particular that of Mycobacterium tuberculosis, the agent of human tuberculosis. The recent availability of genome sequences of several Mycobacterium canettii strains, representing evolutionary early-branching tubercle bacilli, has allowed the genomic and molecular features of the putative ancestor of the M. tuberculosis complex (MTBC) to be reconstituted.

Substrate specificity of MarP, a periplasmic protease required for resistance to acid and oxidative stress in Mycobacterium tuberculosis.

The transmembrane serine protease MarP is important for pH homeostasis in Mycobacterium tuberculosis (Mtb). Previous structural studies revealed that MarP contains a chymotrypsin fold and a disulfide bond that stabilizes the protease active site in the substrate-bound conformation. Here, we determined that MarP is located in the Mtb periplasm and showed that this localization is essential for function.

Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis.

Global spread and limited genetic variation are hallmarks of M. tuberculosis, the agent of human tuberculosis. In contrast, Mycobacterium canettii and related tubercle bacilli that also cause human tuberculosis and exhibit unusual smooth colony morphology are restricted to East Africa.

Disulfide bond formation and ToxR activity in Vibrio cholerae.

Virulence factor production in Vibrio cholerae is complex, with ToxRS being an important part of the regulatory cascade. Additionally, ToxR is the transcriptional regulator for the genes encoding the major outer membrane porins OmpU and OmpT. ToxR is a transmembrane protein and contains two cysteine residues in the periplasmic domain.