Transcriptomic, Functional, and Network Analyses Reveal Novel Genes Involved in the Interaction Between Caenorhabditis elegans and Stenotrophomonas maltophilia.

Corin V White,Michael A Herman

doi:10.3389/fcimb.2018.00266

Abstract

The bacterivorous nematode Caenorhabditis elegans is an excellent model for the study of innate immune responses to a variety of bacterial pathogens, including the emerging nosocomial bacterial pathogen Stenotrophomonas maltophilia. The study of this interaction has ecological and medical relevance as S. maltophilia is found in association with C. elegans and other nematodes in the wild and is an emerging opportunistic bacterial pathogen. We identified 393 genes that were differentially expressed when exposed to virulent and avirulent strains of S. maltophilia and an avirulent strain of E. coli. We then used a probabilistic functional gene network model (WormNet) to determine that 118 of the 393 differentially expressed genes formed an interacting network and identified a set of highly connected genes with eight or more predicted interactions. We hypothesized that these highly connected genes might play an important role in the defense against S. maltophila and found that mutations of six of seven highly connected genes have a significant effect on nematode survival in response to these bacteria. Of these genes, C48B4.1, mpk-2, cpr-4, clec-67, and lys-6 are needed for combating the virulent S. maltophilia JCMS strain, while dod-22 was solely involved in response to the avirulent S. maltophilia K279a strain. We further found that dod-22 and clec-67 were up regulated in response to JCMS vs. K279a, while C48B4.1, mpk-2, cpr-4, and lys-6 were down regulated. Only dod-22 had a documented role in innate immunity, which demonstrates the merit of our approach in the identification of novel genes that are involved in combating S. maltophilia infection.

Highlights

Stenotrophomonas maltophilia is an emerging nosocomial and opportunistic bacterial pathogen associated with mortality rates ranging from14 to 69% in patients with bacteremia (Brooke, 2012)
Previous studies on the interaction of C. elegans with pathogenic bacteria suggested that the accumulation of living bacteria in the intestine plays a large role in nematode pathogenesis (Garsin et al, 2001; Sifri et al, 2005)
We previously observed that the pathogenic S. maltophilia isolate JCMS causes a significantly higher bacterial load 24 h post exposure as compared to other, less virulent S. maltophilia strains and the standard laboratory food E. coli OP50 (White et al, 2016)

Summary

Introduction

Stenotrophomonas maltophilia is an emerging nosocomial and opportunistic bacterial pathogen associated with mortality rates ranging from to 69% in patients with bacteremia (Brooke, 2012). S. maltophilia infections have increased in prevalence among the general population (Chang et al, 2015). These infections can be acquired both in the community (Falagas et al, 2009; Chang et al, 2014) or associated with health care (Garazi et al, 2012). C. elegans Innate Immune Response to S. maltophilia nosocomial pathogens, S. maltophilia is associated with respiratory tract, soft tissue, and skin infections and can exacerbate the effects of other diseases and disorders such as chronic obstructive pulmonary disease (Denton and Kerr, 1998; Brooke, 2012). S. maltophilia is found ubiqutiously, and the presence of intrinsic antibiotic resistance in combination with the recent increase in the prevelance of infections renders the study of its interaction with hosts a major priority

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