Little but lethal: Small RNAs coordinate bacterial attack on epithelial cells
Two small RNAs (sRNAs) working in concert enable the deadly enterohemorrhagic Escherichia coli (EHEC) 0157:H7 to attach to and initiate infection in epithelial cells that line the digestive tract, according to a study published in mBio, the online open-access journal of the American Society for Microbiology.
Gram-negative bacteria such as EHEC enter their prey and deploy syringe-like weapons called type III secretion systems (T3SS) that inject proteins into the epithelial cells to promote reorganization of the the cytoskeleton into pedestals that act as docking stations for the bacteria to adhere to the cells.
Both pedestal and T3SS formation demand rapid activation and precise coordination of a large number of bacterial genes co-opted from a pathogenicity island called the locus of enterocytes effacement (LEE) which Charley Gruber, Vanessa Sperandio and their colleagues at the University of Texas Southwestern Medical School in Dallas recently discovered is orchestrated by two sRNAs known as GlmY and GlmZ.
"Our data reveal two previously unknown mechanisms of actions for these sRNAs," Sperandio says. "Working together GlmY and GlmZ cleave the transcript between espJ and espFu genes enabling translation of EspFu, a protein important for efficient mammalian-cell invasion, and also destabilize the LEE 4 and 5 transcripts thus fine tuning LEE gene expression."
"Destabilization of LEE is especially important for two reasons—first, it permits the differential expression of various genes encoded within the same cluster and second, it ensures that the bacteria are forming optimal pedestal levels on epithelial cells during infection," according to Sperandio. Thus, these researchers propose that these sRNAs are responsible for the dynamic rewiring of the bacterial complex machineries that enable infection.
"This is a very important contribution to the field particularly because it shows that things are more complicated than they initially appeared," comments Petr G. Leiman at École Polytechnique Fédérale de Lausanne in Switzerland. "Studies involving sRNA are tricky and require many controls which this paper appears to present in full, thus making the Sperandio team's work very significant."
"The horizontal acquisitions of pathogenicity islands [such as LEE] with their added virulence genes enable bacteria to exploit additional niches and new hosts," explains Sperandio. "Our results suggest that the interplay between ancient and recent evolutionary acquisitions shaped the EHEC we're dealing with today," Gruber adds. However, the evolution is ongoing and as the Red Queen in Alice in Wonderland so famously said, we have to race ahead just to keep up.