Subcellular organization of small RNAs: The polygenic plan and its impact on bacterial physiology and virulence

The linkage between bacteria and human health is becoming more crucial due to the spread of bacterial resistance to antibiotics. The challenge is to develop alternative treatments that target bacterial unique mechanisms by which bacteria attack their hosts. Some of the mechanisms for attacking and influencing the host involve small RNAs (sRNAs), which mediate the inner bacterial response to environmental stresses, prompt resistance to antibiotics and induce immunological responses that alter the host gene expression profile.

Data from our lab show that upon stress, numerous sRNAs accumulate at the bacterial cell poles via a chaperon-dependent mechanism, most of them not known to be involved in the applied stress (Molecular Cell, in press). Our hypothesis is that accumulation of the sRNA population at the poles is a coordinated polygenic plan intended to enable bacterial adaptation to environment changings, including to the host.

Two lines of preliminary results support the polygenic hypothesis:

1. Transcription of sRNAs unrelated to the stress upon induction of specific stress.

2. A decrease in growth rate and fitness in high osmolarity and in oxidative stress of an unbiasedly-constructed multi-sRNA-knockout (KO) strain, as opposed to wild type-like growth rate and fitness of the single sRNA-KO mutants under the same environmental conditions.

Our aims are to elucidate the mechanism that underlies spatial accumulation of sRNA upon stress / antibiotic treatment and to reveal the sRNA regulatory polygenic plan in bacteria. This research will provide new targets for the development of new-generation anti-microbial treatments.