Low salinity activates a virulence program in the generalist marine pathogen Photobacterium damselae subsp. damselae

Abstract

Facultative marine bacterial pathogens sense environmental signals so that the expression of virulence factors is upregulated on entry into hosts and downregulated during the free-living lifestyle in the environment. In this study, we utilized transcriptome sequencing to compare the transcriptional profiles of Photobacterium damselae subsp. damselae , a generalist pathogen that causes disease in diverse marine animals and fatal infections in humans at NaCl concentrations that mimic the free-living lifestyle or host internal milieu, respectively. We here show that NaCl concentration constitutes a major regulatory signal that shapes the transcriptome and uncover 1,808 differentially expressed genes (888 upregulated and 920 downregulated in response to low-salt conditions). Growth at 3% NaCl, a salinity that mimics the free-living lifestyle, upregulated genes involved in energy production, nitrogen metabolism, transport of compatible solutes, utilization of trehalose and fructose, and carbohydrate and amino acid metabolism with strong upregulation of the arginine deiminase system (ADS). In addition, we observed a marked increase in resistance to antibiotics at 3% NaCl. On the contrary, the low salinity conditions (1% NaCl) that mimic those encountered in the host triggered a virulence gene expression profile that maximized the production of the type 2 secretion system (T2SS)-dependent cytotoxins damselysin, phobalysin P, and a putative PirAB-like toxin, observations that were corroborated by the analysis of the secretome. Low salinity also upregulated the expression of iron-acquisition systems, efflux pumps, and other functions related to stress response and virulence. The results of this study greatly expand our knowledge of the salinity-responsive adaptations of a generalist and versatile marine pathogen. IMPORTANCE Pathogenic Vibrionaceae species experience continuous shifts of NaCl concentration in their life cycles. However, the impact of salinity changes in gene regulation has been studied in a small number of Vibrio species. In this study, we analyzed the transcriptional response of Photobacterium damselae subsp. damselae ( Pdd ), a generalist and facultative pathogen, to changes in salinity, and demonstrate that growth at 1% NaCl in comparison to 3% NaCl triggers a virulence program of gene expression, with a major impact in the T2SS-dependent secretome. The decrease in NaCl concentration encountered by bacteria on entry into a host is proposed to constitute a regulatory signal that upregulates a genetic program involved in host invasion and tissue damage, nutrient scavenging (notably iron), and stress responses. This study will surely inspire new research on Pdd pathobiology, as well as on other important pathogens of the family Vibrionaceae and related taxa whose salinity regulons still await investigation.

Marine diseases and the Anthropocene: Understanding microbial pathogenesis in a rapidly changing world

“…Although these enzymes serve nutritional roles, they may confer a survival advantage when used in conjunction with other adaptive traits, leading to host tissue damage, and as such are termed ‘dual use’ traits (Casadevall et al., 2003 ). Furthermore, microorganisms often modulate the expression of genes in response to external stimuli, and so pathogens may only express virulence phenotypes under changed environmental conditions (Barca et al., 2023 ; Cárdenas et al., 2018 ; Kimes et al., 2012 ). Therefore, identifying pathogens and analysing their virulence potential may require a comprehensive and comparative approach that goes beyond simply endeavouring to fulfil Koch's postulates or inferring virulence based on the presence of archetypal virulence genes.…”

Urbanization of a subtropical island (Okinawa, Japan) alters physicochemical characteristics and disrupts microbial community dynamics in nearshore ecosystems

“…As keystone organisms, coral mortality has downstream ecosystem and economic implications (Moberg and Folke 1999). Moreover, salinity is a major driver for bacterioplankton community composition (Lozupone and Knight 2007;Jurdzinski et al 2023), and reduced salinity in nearshore regions can promote the growth of pathogenic bacteria (Bordalo et al 2002;Randa et al 2004;Burge et al 2014) and increase the pathogenicity of some bacteria (Barca et al 2023).…”