What Is the Link between Stringent Response, Endoribonuclease Encoding Type II Toxin–Antitoxin Systems and Persistence?
Authors: Dimpy Ghosh
Bhaskar C M Ramisetty
Maoumita Roy Chowdhury
Ramachandran S Santhosh
Journal: Frontiers in Microbiology (2016)
Discipline: MICROBIOLOGY
Keywords: fitness; inorganic polyphosphate; polar effects; ppGpp.
Affiliations: School of Chemical and Biotechnology, SASTRA UniversityThanjavur, India; Department of Biochemistry and Molecular Biology, University of Southern DenmarkOdense, Denmark., School of Chemical and Biotechnology, SASTRA University Thanjavur, India.

Abstract:  Persistence is a transient and non-inheritable tolerance to antibiotics by a small fraction of a bacterial population. One of the proposed determinants of bacterial persistence is toxin-antitoxin systems (TASs) which are also implicated in a wide range of stress-related phenomena. Maisonneuve E, Castro-Camargo M, Gerdes K. 2013. Cell 154:1140-1150 reported an interesting link between ppGpp mediated stringent response, TAS, and persistence. It is proposed that accumulation of ppGpp enhances the accumulation of inorganic polyphosphate which modulates Lon protease to degrade antitoxins. The decrease in the concentration of antitoxins supposedly activated the toxin to increase in the number of persisters during antibiotic treatment. In this study, we show that inorganic polyphosphate is not required for transcriptional activation of yefM/yoeB TAS, which is an indirect indication of Lon-dependent degradation of YefM antitoxin. The Δ10 strain, an Escherichia coli MG1655 derivative in which the 10 TAS are deleted, is more sensitive to ciprofloxacin compared to wild type MG1655. Furthermore, we show that the Δ10 strain has relatively lower fitness compared to the wild type and hence, we argue that the persistence related implications based on Δ10 strain are void. We conclude that the transcriptional regulation and endoribonuclease activity of YefM/YoeB TAS is independent of ppGpp and inorganic polyphosphate. Therefore, we urge for thorough inspection and debate on the link between chromosomal endoribonuclease TAS and persistence. 

Retracted: No

PubPeer comments:
  Text Correction In the original article, there was an error. In the text, the diameters of the zones of inhibition given for the strains (MG1655 and u039410) were interchanged. A correction has been made to Results and Discussion, Sub-section Relative Hypersensitivity of MG1655 and u039410 Strains to Ciprofloxacin and Ampicillin, Paragraph one: In light of our observations, we were curious about the degree of sensitivity to various antibiotics. We determined the sensitivity of the MG1655 and u039410 strains to various antibiotics by disk diffusion method, as it is highly sensitive and quantifiable. We observed that the zone of inhibition of MG1655 with ciprofloxacin (10 u03bcg) was 3 cm (averages) while that of u039410 strain was 3.6 cm (Figure 3B). With ampicillin (10 u03bcg), the zones of inhibition for MG1655 and u039410 strain were 2.1 cm and 2.45 cm, respectively. With nalidixic acid, the zones of inhibition for MG1655 and u039410 strain were 1.78 and 1.98 cm, respectively. We did not find any significant difference with the other antibiotics at the concentrations used (Figures 3B,C). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. ,