Translational Fidelity during Bacterial Stresses and Host Interactions

Abstract

Translational fidelity refers to accuracy during protein synthesis and is maintained in all three domains of life. Translational errors occur at base levels during normal conditions and may rise due to mutations or stress conditions. In this article, we review our current understanding of how translational fidelity is perturbed by various environmental stresses that bacterial pathogens encounter during host interactions. We discuss how oxidative stress, metabolic stresses, and antibiotics affect various types of translational errors and the resulting effects on stress adaption and fitness. We also discuss the roles of translational fidelity during pathogen–host interactions and the underlying mechanisms. Many of the studies covered in this review will be based on work with Salmonella enterica and Escherichia coli, but other bacterial pathogens will also be discussed.

Interplay between mistranslation and oxidative stress in Escherichia coli

“…In general, mistranslation has toxic effect on cells and organisms ( 16 , 17 , 18 ), but some translational errors can be beneficial for a cell or organism under certain stress conditions ( 26 ). For example, global mistranslation of any amino acid caused by ribosomal errors leads to an increased expression of the sigma factor RpoS, a subunit of bacterial RNA-polymerase that directs RNA-polymerase to the promoters of genes associated with stress response ( 49 ).…”

“…However, there are several examples in which mistranslation has a beneficial effect ( 25 , 26 ). Naturally occurring mistranslation of specific amino acids can be induced as part of response to stress.…”

“…Constitutively higher mistranslation rates are common in parasites, such as Mycoplasma ( 29 , 30 ) and mycobacterial pathogens ( 31 ), which are associated with antibiotic resistance and may lead to antigen diversity, enabling pathogens to escape the host's immune system. In some cases, mistranslation induces general stress response, resulting in tolerance to other stress conditions ( 25 , 26 ).…”

Evolution and variation in amide aminoacyl‐tRNA synthesis

“…There is growing evidence that physiological stress in bacteria can lead to mistranslation, with a greater appreciation that species are more tolerant to mistranslation than initially thought and in fact may even be beneficial under certain conditions by increasing protein variation. 19,153,[155][156][157][158][159][160][161][162][163][164] Mistranslation in mycobacteria is associated with increased resistance to the antibiotic rifampicin, with mistranslation increasing in the stationary phase compared to log phase growth and when the pH is lower. 158 Mycobacteria lack both AsnRS and GlnRS.…”

Mistranslation of the genetic code by a new family of bacterial transfer RNAs

“…Similarly, global mistranslation with Met can protect mammalian and bacterial cells against oxidative stress ( 14 , 15 ), while the opportunistic human pathogen Candida albicans mistranslates Leu codons with Ser as a mechanism to escape the host’s immune response ( 16 , 17 , 18 , 19 ). Several other examples of mistranslation as a mechanism of cellular resiliency and survival have been described ( 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ).…”