A horizontally acquired tRNA facilitates Coxiella burnetii adaptation to an extreme environment.

2014-08-24T18:55:00Z (GMT) by Jess Millar Rahul Raghavan

Coxiella burnetii is an obligate intracellular bacterium that lives inside parasitophorous vacuoles (PV) derived from lysosomes. The PV is acidic (~4.5 pH) and Coxiella is the only bacterium known to thrive in this extreme environment. However, the metabolic adaptations that allow Coxiella to replicate in this niche are unknown. Coxiella has a highly reduced genome due to lack of selection pressure to maintain superfluous genes; however, it has retained an extra copy of tRNAGlu. Horizaontal gene transfer is the likely origin of the additional isoacceptor (tRNAGlu2) present in Coxiella as it is not present in other Gammaproteobacteria. In this study, C. burnetii was grown in THP-1 cells and High Throughput Sequencing was used to examine tRNA isoacceptors and measure gene expression values for all genes. All heme biosynthesis genes and tRNAGlu2 were highly expressed in Coxiella during intracellular growth. Coxiella lacks heme transporters but has ferrous ion transporters. This is the major iron form found in the highly acidic PV, and the form used in heme biosynthesis. Additionally, tRNAGlu2 can only decode the GAG codon but the prevalence of GAA codons in proteins was three times higher than that of GAG codons. tRNAGlu not only has a role in protein biosynthesis, but it’s also the starting point for heme biosynthesis. Many bacteria obtain heme from their environment using heme transporters, however these are missing in Coxiella. The high expression of both heme biosynthesis genes and tRNAGlu2 highlights its importance, likely due to heme’s vital role in respiration and other processes. With the prevalence of GAA codons three times that of GAG, which only tRNAGlu1 can decode, we hypothesize that the primary role of tRNAGlu2 in Coxiella is heme biosynthesis and not translation. Our next steps will be to construct gene deletion strains of Coxiella and examine the importance of tRNAGlu2 and heme biosynthesis for Coxiella’s intracellular growth and virulence. The first two enzymes (HemA and HemL) in Coxiella’s heme biosynthesis process are not found in humans; hence they are attractive targets for developing novel antibiotics to treat Coxiella. This is significant as current antibiotics are not very effective against chronic endocarditis caused by Coxiella and resistance to these antibiotics is prevalent among clinical strains.



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