Adaptive Changes in Mycobacterium avium Gene Expression Profile Following Infection of Genetically Susceptible and Resistant Mice

Abstract

We performed a comparative analysis ofMycobacterium aviumtranscriptomes (strain 724R) in infected mice of two different strains- resistant and susceptible to infection. Sets of mycobacterial genes transcribed in lung tissue were defined, and differentially transcribed genes were revealed. Our results indicate thatM. aviumgenes coding for enzymes of the Krebs cycle, oxidative phosphorylation, NO reduction, fatty acid biosynthesis, replication, translation, and genome modification are expressed at high levels in the lungs of genetically susceptible mice. The expression of genes responsible for cell wall properties, anaerobic nitrate respiration, fatty acid degradation, synthesis of polycyclic fatty acid derivatives, and biosynthesis of mycobactin and other polyketides is increased in the resistant mice. In the resistant host environment,Mycobacterium aviumapparently transitions to a latent state caused by the deficiency in divalent cations and characterised by anaerobic respiration, degradation of fatty acids, and modification of cell wall properties.

Keywords: transcriptome analysisin vivo; Mycobacterium avium; RNA-seq; coincidence cloning.

Fig. 1

Coincidence cloning. Suppressive oligonucleotide adapters are ligated to fragments of bacterial genomic DNA and total cDNA. The samples are mixed, denatured, and slowly renatured, which leads to the formation of two types of duplexes. Due to selective suppression of PCR, only heteroduplexes containing fragments of bacterial genomic DNA and bacterial cDNA are amplified.

Fig. 2

M. avium metabolic state in the lungs of the I/St and B6 mice