Escherichia coli YafP protein modulates DNA damaging property of the nitroaromatic compounds

Abstract

Escherichia coli SOS functions constitute a multifaceted response to DNA damage. We undertook to study the role of yafP, a SOS gene with unknown function. yafP is part of an operon also containing the dinB gene coding for DNA Polymerase IV (PolIV). Our phylogenetic analysis showed that the gene content of this operon is variable but that the dinB and the yafP genes are conserved in the majority of E. coli natural isolates. Therefore, we studied if these proteins are functionally linked. Using a murine septicaemia model, we showed that YafP activity reduced the bacterial fitness in the absence of PolIV. Similarly, YafP increased cytotoxicity of two DNA damaging nitroaromatic compounds, 4-nitroquinoline-1-oxide (NQO) and nitrofurazone, in the absence of PolIV. The fact that PolIV counterbalances YafP-induced cytotoxicity could explain why these two genes are transcriptionally linked. We also studied the involvement of YafP in genotoxic-stress induced mutagenesis and found that PolIV and YafP reduced NQO-induced mutagenicity. The YafP antimutator activity was independent of the PolIV activity. Given that YafP was annotated as a putative acetyltransferase, it could be that YafP participates in the metabolic transformation of genotoxic compounds, hence modulating the balance between their mutagenicity and cytotoxicity.

Urinary tract infection drives genome instability in uropathogenicEscherichia coliand necessitates translesion synthesis DNA polymerase IV for virulence

“…Parallel to our report, Gutierrez et al recently showed that the absence of DinB resulted in loss of fitness in competive infections with wt UPEC CFT073 in a murine model of bacteremia, 49 consistent with our demonstration of a role of DinB in UTI pathogenesis. In that report, the authors demonstrate that the attenuated phenotype of the dinB mutant was restored when the yafP gene, encoding for an N-acetyltransferase, was also deleted.…”

Translesion DNA Synthesis

“…S.typhimurium dinB is located at 7.2 mins and lacks the downstream yafN, yafO and yafP genes but is, instead, flanked by the yafK and prfH genes. The lack of a downstream yafP gene is intriguing as the operon arrangement is apparently conserved in a number of naturally occurring E.coli and YafP seems to work with DinB to protect cells from cytotoxic effects of exposure to nitroaromatic compounds (88). Despite the lack of an obvious dinB-yafN-yafO-yafP operon in S. typhimurium , its dinB gene is nevertheless located in a similar genomic region to E.coli dinB , since four genes upstream of the E. coli yafM gene is the yafK gene and 1.4 kb downstream of the yafN gene is a prfH -like pseudogene (Fig.…”

Quick replication fork stop by overproduction of <i>Escherichia coli</i> DinB produces non-proliferative cells with an aberrant chromosome

“…In addition to mazF and relE, no single deletion of other known type II toxin genes (chpB, hipA, yoeB and yafQ) in MK70101/pDB10 was able to overcome the lethality of DinB overproduction (data . dinB constitutes an operon together with the recently discovered toxin-antitoxin module yafNO (Singletary et al, 2009) and yafP, which encodes a putative acetyltransferase that is proposed to work together with dinB in recovery from genotoxic shock (Gutierrez et al, 2011). Deletion of yafNOP from the dinB operon also had no effect on the reduction in CFU (Fig.…”