Molecular and functional profiling of the polyamine content in enteroinvasive E. coli : looking into the gap between commensal E. coli and harmful Shigella.

Rosaria Campilongo,Lucia Marcocci,Bianca Colonna,Mauro Nicoletti,Paola Pietrangeli,Adriano Leuzzi,Milena Grossi,Gioacchino Micheli,Gianni Prosseda,Maria Letizia Di Martino,Mariassunta Casalino

doi:10.1371/journal.pone.0106589

Rosaria Campilongo, Lucia Marcocci + Show 9 more

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https://doi.org/10.1371/journal.pone.0106589

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Abstract

Polyamines are small molecules associated with a wide variety of physiological functions. Bacterial pathogens have developed subtle strategies to exploit polyamines or manipulate polyamine-related processes to optimize fitness within the host. During the transition from its innocuous E. coli ancestor, Shigella, the aetiological agent of bacillary dysentery, has undergone drastic genomic rearrangements affecting the polyamine profile. A pathoadaptation process involving the speG gene and the cad operon has led to spermidine accumulation and loss of cadaverine. While a higher spermidine content promotes the survival of Shigella within infected macrophages, the lack of cadaverine boosts the pathogenic potential of the bacterium in host tissues. Enteroinvasive E. coli (EIEC) display the same pathogenicity process as Shigella, but have a higher infectious dose and a higher metabolic activity. Pathoadaption events affecting the cad locus have occurred also in EIEC, silencing cadaverine production. Since EIEC are commonly regarded as evolutionary intermediates between E. coli and Shigella, we investigated on their polyamine profile in order to better understand which changes have occurred along the path to pathogenicity. By functional and molecular analyses carried out in EIEC strains belonging to different serotypes, we show that speG has been silenced in one strain only, favouring resistance to oxidative stress conditions and survival within macrophages. At the same time, we observe that the content of spermidine and putrescine, a relevant intermediate in the synthesis of spermidine, is higher in all strains as compared to E. coli. This may represent an evolutionary response to the lack of cadaverine. Indeed, restoring cadaverine synthesis decreases the expression of the speC gene, whose product affects putrescine production. In the light of these results, we discuss the possible impact of pathoadaptation events on the evolutionary emergence of a polyamine profile favouring to the pathogenic lifestyle of Shigella and EIEC.

Highlights

Escherichia coli is a harmless commensal of the human and animal intestine, and a major cause of morbidity and mortality [1,2]
We have investigated on the polyamine profile in Enteroinvasive E. coli (EIEC) in order to understand whether, besides cad genes, other genes involved in polyamine metabolism had been lost during pathoadaptation
The results we present reveal that EIEC have an intermediate polyamine content as compared to E. coli and Shigella and that cadaverine negatively affects the synthesis of putrescine

Summary

Introduction

Escherichia coli is a harmless commensal of the human and animal intestine, and a major cause of morbidity and mortality [1,2]. As in many other bacterial pathogens, the evolution of E. coli towards pathogenic phenotypes has been determined mainly by two mechanisms: the acquisition of virulence genes and the loss or modification of genes of the core genome [3]. On the basis of specific virulence factors and pathogenicity processes, pathogenic E. coli have been subdivided into different pathotypes, including intestinal and extraintestinal strains [1]. Among intestinal pathogenic E. coli, enteroinvasive E. coli (EIEC) are intracellular pathogens causing a severe enteric syndrome in humans, mainly in developing countries [5]. The mechanism is similar to that of Shigella, the causative agent of bacillary dysentery [8] and EIEC strains are included in the same pathotype as Shigella [1]. In contrast to Shigella, EIEC have a higher infectious dose and a higher metabolic activity, retaining the ability to catabolize substrates widely used by E. coli [10,13,14]

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