Research Article: A Phylogenetic and Phenotypic Analysis of Salmonella enterica Serovar Weltevreden, an Emerging Agent of Diarrheal Disease in Tropical Regions

Date Published: February 11, 2016

Publisher: Public Library of Science

Author(s): Carine Makendi, Andrew J. Page, Brendan W. Wren, Tu Le Thi Phuong, Simon Clare, Christine Hale, David Goulding, Elizabeth J. Klemm, Derek Pickard, Chinyere Okoro, Martin Hunt, Corinne N. Thompson, Nguyen Phu Huong Lan, Nhu Tran Do Hoang, Guy E. Thwaites, Simon Le Hello, Anne Brisabois, François-Xavier Weill, Stephen Baker, Gordon Dougan, Edward T. Ryan.

Abstract: Salmonella enterica serovar Weltevreden (S. Weltevreden) is an emerging cause of diarrheal and invasive disease in humans residing in tropical regions. Despite the regional and international emergence of this Salmonella serovar, relatively little is known about its genetic diversity, genomics or virulence potential in model systems. Here we used whole genome sequencing and bioinformatics analyses to define the phylogenetic structure of a diverse global selection of S. Weltevreden. Phylogenetic analysis of more than 100 isolates demonstrated that the population of S. Weltevreden can be segregated into two main phylogenetic clusters, one associated predominantly with continental Southeast Asia and the other more internationally dispersed. Subcluster analysis suggested the local evolution of S. Weltevreden within specific geographical regions. Four of the isolates were sequenced using long read sequencing to produce high quality reference genomes. Phenotypic analysis in Hep-2 cells and in a murine infection model indicated that S. Weltevreden were significantly attenuated in these models compared to the classical S. Typhimurium reference strain SL1344. Our work outlines novel insights into this important emerging pathogen and provides a baseline understanding for future research studies.

Partial Text: Salmonella enterica is a globally distributed Gram-negative enteric bacterial species that is responsible for significant levels of morbidity and mortality in both humans and animals [1]. S. enterica is currently classified into six subspecies and >2,500 serovars on the basis of the White- Kauffmann-Le Minor scheme that exploits specific typing sera against O (lipopolysaccharide) and H (flagella) antigens [2]. S. enterica organisms can also be loosely assigned into the so called typhoidal or non-typhoidal Salmonella (NTS) serovars. Typhoidal Salmonella are typically adapted to cause systemic disease in humans e.g. Salmonella enterica serovar Typhi (S. Typhi) the cause of the typhoid fever [3,4]. In contrast, NTS are more frequently, but not exclusively, associated with localized gastroenteritis and are more promiscuous and zoonotic than typhoidal serovars, and can infect multiple hosts e.g. S. Typhimurium [5,6]. Genetically, S. enterica is regarded as a broad and ancient species; different serovars/isolates can vary by 100,000s of single nucleotide polymorphisms (SNPs) and contain a variable array of genomic islands and prophages [7,8]. Further, many Salmonella serovars are monomorphic or clonal [6,9], however, there can be significant genetic diversity within a specific serovar e.g. S. Typhimurium [10] and generally studies on genetic diversity within a particular serovar are scarce, particularly using newer high-throughput approaches such as whole genome sequencing.

In this study, a combination of WGS, phylogenetic and in-vitro/in-vivo phenotyping were used to characterize the emerging Salmonella serovar S. Weltevreden. Additionally, four reference genomes (and corresponding reference strains) that will be of value for further genetic and genomic work on this increasing important serovar were generated. Our analysis revealed that the S. Weltevreden genome is larger than those of many other S. enterica serovars with a mean size over five million basepairs. Much of this additional genetic material was attributed to the accessory genome, where complete prophage and additional prophage-related elements were found to be common. Another little known serovar—S. Elisabethville, was found to be phylogenetically closest S. enterica serovar to S. Weltevreden. Remarkably, S. Elisabethville shares core serological properties with S. Weltevreden, but S. Elisabethville is not a common pathogen in humans. It will be interesting to see if this related serovar emerges in humans in the future, as has been the case for S. Weltevreden.



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