Stepwise pathogenic evolution of Mycobacterium abscessus

Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as Mycobacterium tuberculosis, have evolved to cause transmissible human infection. By analyzing the recent emergence and spread of the environmental organism M. abscessus through the global cystic fibrosis population, we have defined key, generalizable steps involved in the pathogenic evolution of mycobacteria. We show that epigenetic modifiers, acquired through horizontal gene transfer, cause saltational increases in the pathogenic potential of specific environmental clones. Allopatric parallel evolution during chronic lung infection then promotes rapid increases in virulence through mutations in a discrete gene network; these mutations enhance growth within macrophages but impair fomite survival. As a consequence, we observe constrained pathogenic evolution while person-to-person transmission remains indirect, but postulate accelerated pathogenic adaptation once direct transmission is possible, as observed for M. tuberculosis. Our findings indicate how key interventions, such as early treatment and cross-infection control, might restrict the spread of existing mycobacterial pathogens and prevent new, emergent ones.

Type I Interferon Signature in Chilblain-Like Lesions Associated with the COVID-19 Pandemic

Contemporarily to the new SARS-CoV-2 mediated COVID-19 pandemic, a rise in patients with acral chilblain lesions has been described. They manifest late after mild disease or asymptomatic exposure to SARS-CoV-2. Their pathogenic evolution is currently unknown. In biopsies from three patients with acral partially ulcerating chilblain lesions that occurred associated to the COVID-19 pandemic, we analysed the expression of type I interferon induced proteins and signal transduction kinases. Histology demonstrated perivascular and periadnexal lymphohistiocytic infiltrates and endothelial dominated MxA-staining, as well as pJAK1 activation. Our findings demonstrate induction of the type I IFN pathway in lesional sections of COVID-19-associated chilblain-like lesions. This may indicate a local antiviral immune activation status associated with preceding exposure to SARS-CoV-2.

HOLISTIC APPROACH IN DEALING WITH MENTAL STRESS DURING COVID-19 PANDEMIC: A REVIEW

This review article is based on the holistic methods which can be helpful in maintaining mental stress caused by different reasons like lockdown, economic conditions, stress due to social distancing, stress due to lack of work, family disputes due to lockdown, no work and to protect physical health etc.An emotional turmoil is there in the mind of lots of people because of the current unavoidable circumstances created due to pandemic COVID 19.A much-needed approach in improving mental health is required for unavoidable circumstances like epidemics,violence etc.Holistic approach is beneficial because medicines for mental disorders have side effects like addiction.The World Health Organization (WHO) defines holistic health as:Viewing man in his totality within a wide ecological spectrum, and emphasizing the view that ill health or disease is brought about by an imbalance, or disequilibrium, of man in his total ecological system and not only by the causative agent and pathogenic evolution.

Contribution of Gene Loss to the Pathogenic Evolution of Burkholderia pseudomallei and Burkholderia mallei

ABSTRACT Burkholderia pseudomallei is the causative agent of melioidosis. Burkholderia thailandensis is a closely related species that can readily utilize l-arabinose as a sole carbon source, whereas B. pseudomallei cannot. We used Tn5-OT182 mutagenesis to isolate an arabinose-negative mutant of B. thailandensis. Sequence analysis of regions flanking the transposon insertion revealed the presence of an arabinose assimilation operon consisting of nine genes. Analysis of the B. pseudomallei chromosome showed a deletion of the operon from this organism. This deletion was detected in all B. pseudomallei and Burkholderia mallei strains investigated. We cloned the B. thailandensis E264 arabinose assimilation operon and introduced the entire operon into the chromosome of B. pseudomallei 406e via homologous recombination. The resultant strain, B. pseudomallei SZ5028, was able to utilize l-arabinose as a sole carbon source. Strain SZ5028 had a significantly higher 50% lethal dose for Syrian hamsters compared to the parent strain 406e. Microarray analysis revealed that a number of genes in a type III secretion system were down-regulated in strain SZ5028 when cells were grown in l-arabinose, suggesting a regulatory role for l-arabinose or a metabolite of l-arabinose. These results suggest that the ability to metabolize l-arabinose reduces the virulence of B. pseudomallei and that the genes encoding arabinose assimilation may be considered antivirulence genes. The increase in virulence associated with the loss of these genes may have provided a selective advantage for B. pseudomallei as these organisms adapted to survival in animal hosts.