PaeA (YtfL) protects from cadaverine and putrescine stress in Salmonella Typhimurium and E. coli

Abstract

Salmonella and E. coli synthesize, import, and export cadaverine, putrescine, and spermidine to maintain physiological levels and provide pH homeostasis. Both low and high intracellular levels of polyamines confer pleiotropic phenotypes or lethality. Here, we demonstrate that the previously uncharacterized inner membrane protein PaeA (YtfL) is required for reducing cytoplasmic cadaverine and putrescine concentrations. We identified paeA as a gene involved in stationary phase survival when cells were initially grown in acidic medium, in which they produce cadaverine. The paeA mutant is also sensitive to putrescine, but not to spermidine or spermine. Sensitivity to external cadaverine in stationary phase is only observed at pH > 8, suggesting that the polyamines need to be deprotonated to passively diffuse into the cell cytoplasm. In the absence of PaeA, intracellular polyamine levels increase and the cells lose viability. Degradation or modification of the polyamines is not relevant. Ectopic expression of the known cadaverine exporter, CadB, in stationary phase partially suppresses the paeA phenotype, and overexpression of PaeA in exponential phase partially complements a cadB mutant grown in acidic medium. These data support the hypothesis that PaeA is a cadaverine/putrescine exporter, reducing potentially toxic levels under certain stress conditions.

Physiological Functions of Bacterial “Multidrug” Efflux Pumps

“…In recent research, a previously uncharacterized membrane protein, PaeA (YtfL) of E. coli and Salmonella, was found to have a likely function in the efflux of the diamines putrescine and cadaverine. 417 Mutants of paeA were seen to accumulate higher concentrations of cadaverine and putrescine and are less tolerant to these diamines under defined environmental conditions. 417 Similar to proteins in the SMR and PACE families, PaeA is predicted to have four TM helices but it is significantly longer (∼450 amino acid residues) than proteins classified in either of these two families and contains defined extramembranous domains that are not seen in the SMR or PACE proteins.…”

“…417 Mutants of paeA were seen to accumulate higher concentrations of cadaverine and putrescine and are less tolerant to these diamines under defined environmental conditions. 417 Similar to proteins in the SMR and PACE families, PaeA is predicted to have four TM helices but it is significantly longer (∼450 amino acid residues) than proteins classified in either of these two families and contains defined extramembranous domains that are not seen in the SMR or PACE proteins. Therefore, PaeA could represent a new class of polyamine export protein.…”

“…In recent research, a previously uncharacterized membrane protein, PaeA (YtfL) of E. coli and Salmonella, was found to have a likely function in the efflux of the diamines putrescine and cadaverine . Mutants of paeA were seen to accumulate higher concentrations of cadaverine and putrescine and are less tolerant to these diamines under defined environmental conditions .…”

Metatranscriptome sequencing identifies Escherichia are major contributors to pathogenic functions and biofilm formation in diabetes related foot osteomyelitis

“…Analysis of pathogenicity factors identified ytfL , and relE transcripts within the majority of DFO samples. Iwadate et al reported that ytfL expression facilitates cell viability of E. coli and S. typhirium when exposed to polyamines such as putrescine and cadaverine, both of which are abundant within necrotic diabetes related foot ulcers (Iwadate et al, 2021 ). Previous studies have reported that relE overexpression results in reduced bacterial growth and increased persister cell formation in Xylella fastidiosa and E. coli (Tashiro et al, 2012 ; Burbank and Stenger, 2017 ).…”

Alkaline Stress Causes Changes in Polyamine Biosynthesis in Thermus thermophilus

“…These mechanisms are known to trigger the expression of a specific battery of genes ( speF , cadA , cadB and paeA , etc. ), and specific polyamines synthesized are involved in, for example, the blockage of porins and a decrease in membrane permeability [ 9 , 10 ].…”