Mycoplasma penetrans keeps a double-sized enzyme that appears to make its own methionine

Gene loss is the usual direction of travel for a bacterium with a shrunken genome, and M. penetrans leans on its human host for many genes it does not carry itself ^[4]. It kept one large protein anyway. Methionyl-tRNA synthetase, the enzyme that attaches methionine to its tRNA partner, is twice the size of the E. coli equivalent ^[5][6]. At that ratio, about half the M. penetrans protein has no counterpart in the standard bacterial enzyme ^[19]. Alexander's group reports the surplus appears to run a second reaction, synthesizing methionine ^[7]. In a host cell where methionine is scarce, that could keep the pathogen going ^[8].

The target Alexander names is that extra domain, not the spear the bacterium uses to get inside ^[11][2]. She described the domain as something like an accident of evolution that the bacterium held onto because it turned out to be useful, and said that having it gives a distinct target for inhibiting this pathogen ^[11]. The research "just expands the possibilities of antibacterial therapies," Alexander said ^[18].

Seeing the domain required a structure. That came from a collaboration with Elizabeth Stroupe, a 1997 Wake Forest alumna now a professor of biological sciences at Florida State University, who brought cryo-electron microscopy to mapping the enzyme ^[12]. The PLOS One paper, first-authored by Behrouz Ghazi Esfahani, reports in its title that the synthetase dimerizes via tandem N-terminal ancillary domains ^[16]. Alexander and Stroupe wrote it with their graduate students ^[13], and they are still looking for methods to model the complex structure more comprehensively ^[15].

"Having the structure of M. penetrans MetRS helps us take the next step of understanding the function better," Alexander said ^[14].

The thing this doesn't tell you is whether the domain can be drugged. As reported, the work carries no candidate inhibitor, no potency figure, no selectivity test against a host cell's own charging enzyme, and no animal experiment ^[22]. Selectivity is the part worth watching, because roughly 20 amino acid families each need their own charging enzyme and every cell runs that chemistry ^[17][20]; the second domain is the piece with no E. coli counterpart ^[19]. Delivery sits on top of that. A bacterium living inside a human cell can only be reached by a compound that gets inside the cell too ^[21]. The published result is a structure and a proposed second function, obtained from an organism first noticed as a co-infection in immunocompromised patients with HIV ^[9][3].