Life on arginine for Mycoplasma hominis: clues from its minimal genome and comparison with other human urogenital mycoplasmas

Abstract

Mycoplasma hominis is an opportunistic human mycoplasma. Two other pathogenic human species, M. genitalium and Ureaplasma parvum, reside within the same natural niche as M. hominis: the urogenital tract. These three species have overlapping, but distinct, pathogenic roles. They have minimal genomes and, thus, reduced metabolic capabilities characterized by distinct energy-generating pathways. Analysis of the M. hominis PG21 genome sequence revealed that it is the second smallest genome among self-replicating free living organisms (665,445 bp, 537 coding sequences (CDSs)). Five clusters of genes were predicted to have undergone horizontal gene transfer (HGT) between M. hominis and the phylogenetically distant U. parvum species. We reconstructed M. hominis metabolic pathways from the predicted genes, with particular emphasis on energy-generating pathways. The Embden-Meyerhoff-Parnas pathway was incomplete, with a single enzyme absent. We identified the three proteins constituting the arginine dihydrolase pathway. This pathway was found essential to promote growth in vivo. The predicted presence of dimethylarginine dimethylaminohydrolase suggested that arginine catabolism is more complex than initially described. This enzyme may have been acquired by HGT from non-mollicute bacteria. Comparison of the three minimal mollicute genomes showed that 247 CDSs were common to all three genomes, whereas 220 CDSs were specific to M. hominis, 172 CDSs were specific to M. genitalium, and 280 CDSs were specific to U. parvum. Within these species-specific genes, two major sets of genes could be identified: one including genes involved in various energy-generating pathways, depending on the energy source used (glucose, urea, or arginine) and another involved in cytadherence and virulence. Therefore, a minimal mycoplasma cell, not including cytadherence and virulence-related genes, could be envisaged containing a core genome (247 genes), plus a set of genes required for providing energy. For M. hominis, this set would include 247+9 genes, resulting in a theoretical minimal genome of 256 genes.

Figure 1. Comparative analysis of the genomes of three minimal mollicutes affecting humans.

(A) Number of specific and shared CDSs for the genomes of M. hominis PG21, M. genitalium G37, and U. parvum serovar 3. (B) Focus on known species-specific proteins involved in cytadherence/virulence and energy-generating pathways. LMP, large membrane protein; PTS, phosphoenolpyruvate phosphotransferase system; HGT, horizontal gene transfer; UP, U. parvum; MH, M. hominis; MG, M. genitalium.

Figure 2. Comparison of carbohydrate- and arginine-metabolism pathways and transporters encoded by M. hominis PG21, M. genitalium G37, and U. parvum serovar 3.

Metabolic products are shown in black. Putative proteins present in M. hominis are shown in green; proteins absent from M. hominis are shown in red. “MG” in purple boxes indicates that the gene encoding the corresponding protein is present in the M. genitalium G37 genome. “UP” in blue boxes means that the gene encoding the corresponding protein is present in the U. parvum genome. Transporters are colored according to their substrates: yellow, cations; green, anions and amino-acids; orange, carbohydrates; purple, multidrug and metabolic end product efflux. Arrows indicate the direction of substrate transport.