The bacterial translation stress response

Abstract

Throughout their life, bacteria need to sense and respond to environmental stress. Thus, such stress responses can require dramatic cellular reprogramming, both at the transcriptional as well as the translational level. This review focuses on the protein factors that interact with the bacterial translational apparatus in order to respond to and cope with different types of environmental stress. For example, the stringent factor RelA interacts with the ribosome to generate ppGpp under nutrient deprivation, whereas a variety of factors have been identified that bind to the ribosome under unfavorable growth conditions to shut-down (RelE, pY, RMF, HPF and EttA) or re-program (MazF, EF4 and BipA) translation. Additional factors have been identified that rescue ribosomes stalled due to stress-induced mRNA truncation (tmRNA, ArfA, ArfB), translation of unfavorable protein sequences (EF-P), heat shock induced subunit dissociation (Hsp15) or antibiotic inhibition (TetM, FusB). Understanding the mechanism of how the bacterial cell responds to stress will not only provide fundamental insight into translation regulation, but will also be an important step to identifying new targets for the development of novel antimicrobial agents.

Structure of BipA in GTP form bound to the ratcheted ribosome

“…In contrast, the binding of EF4 induces a clockwiseratcheted ribosome presumably underlying its unique function in back translocation (2,25). Nevertheless, both BipA and EF4 confer a growth advantage to bacteria under stress conditions, and appear to regulate translation of specific but distinct subsets of mRNAs (1). Perhaps the diverse stress-response functions of BipA and EF4 result from the varied location of their CTD in PTC (A site and P site, respectively), leading to interfering with different targets.…”

“…These factors catalyze major steps in translation initiation, elongation (both decoding and mRNA-tRNA complex translocation), and termination, in a GTP-dependent manner. Several additional GTPase factors, including EF4 (formerly known as LepA), BipA, and RelA, have been revealed to be associated with ribosomes under stress conditions (1).…”

“…As is the case with EF4, BipA is not required under optimal growth conditions but becomes an essential factor for bacterial survival at low temperature, nutrient depletion, and various other stress conditions (1,9). The diverse nature of these processes underscores the global regulatory properties of BipA.…”

Role of a ribosomal RNA phosphate oxygen during the EF-G–triggered GTP hydrolysis

“…I n all three domains of life, translational GTPases (trGTPases), highly conserved members of the G protein family, play diverse and central roles during protein biosynthesis (1)(2)(3). G proteins can be regarded as molecular switches that are driven by GTP hydrolysis and cycle between the active GTP-bound state and the inactive GDP-bound form.…”

Implicancias Estructurales y Fisiológicas de la Célula Bacteriana en los Mecanismos de Resistencia Antibiótica

“…Las proteínas codificadas por estos genes interactúan con proteínas ubicadas dentro del ribosoma, causando un cambio conformacional del sitio primario de unión de las tetraciclinas, promoviendo su liberación desde el ribosoma. (Roberts, 2005, Mosquito et al;Dönhöfer et al;Starosta et al, 2014). La resistencia a ácido fusídico por medio de mutaciones FUS-B impide la inhibición de la sín-tesis proteica, liberando estructuras secundarias mRNA secuestradas por efecto del fármaco.…”