Molecular characterization of vulnibactin biosynthesis in Vibrio vulnificus indicates the existence of an alternative siderophore

Abstract

Vibrio vulnificus is a halophilic estuarine bacterium that causes fatal septicemia and necrotizing wound infections in humans. Virulent V. vulnificus isolates produce a catechol siderophore called vulnibactin, made up of one residue of 2, 3-dihydroxybenzoic acid (2, 3-DHBA) and two residues of salicylic acid (SA). Vulnibactin biosynthetic genes (VV2_0828 to VV2_0844) are clustered at one locus of chromosome 2, expression of which is significantly up-regulated in vivo. In the present study, we decipher the biosynthetic network of vulnibactin, focusing specifically on genes around SA and 2, 3-DHBA biosynthetic steps. Deletion mutant of isochorismate pyruvate lyase (VV2_0839) or 2, 3-dihydroxybenzoate-2, 3-dehydrogenase (VV2_0834) showed retarded growth under iron-limited conditions though the latter showed more significant growth defect than the former, suggesting a dominant role of 2, 3-DHBA in the vulnibactin biosynthesis. A double deletion mutant of VV2_0839 and VV2_0834 manifested additional growth defect under iron limitation. Though the growth defect of respective single deletion mutants could be restored by exogenous SA or 2, 3-DHBA, only 2, 3-DHBA could rescue the double mutant when supplied alone. However, double mutant could be rescued with SA only when hydrogen peroxide was supplied exogenously, suggesting a chemical conversion of SA to 2, 3-DHBA. Assembly of two SA and one 2, 3-DHBA into vulnibactin was mediated by two AMP ligase genes (VV2_0836 and VV2_0840). VV2_0836 deletion mutant showed more significant growth defect under iron limitation, suggesting its dominant function. In conclusion, using molecular genetic analytical tools, we confirm that vulnibactin is assembled of both 2, 3-DHBA and SA. However, conversion of SA to 2, 3-DHBA in presence of hydrogen peroxide and growth profile of AMP ligase mutants suggest a plausible existence of yet unidentified alternative siderophore that may be composed solely of 2, 3-DHBA.

Temporal variations in patterns ofEscherichia colistrain diversity and antimicrobial resistance in the migrant Egyptian vulture

“…2) of these strains suggest that, apart from imparting resistance determinants, the dump did act as a ‘melting pot’ of antimicrobial resistance with the potential to disseminate resistant E. coli to multiple geographical locations (breeding grounds of the vultures) corroborating the contention of [12]. …”

“…Also, more synanthropic bird species show increased multidrug resistance E. coli [10,11]. Wild vertebrate species, especially those that use human-dominated landscapes as part of their life history, are therefore likely to be ‘reservoirs and melting pots of bacterial resistance’ with increasing potential of resistant E. coli colonizing intestine and resulting in antimicrobial resistant infections if they end up in urinary tract or the bloodstream adding concern to human health [4,12]. …”

Pediatric obesity is associated with an altered gut microbiota and discordant shifts in Firmicutes populations

“…Indicator species analysis was performed using the indicspecies package (De Caceres et al ., 2009). Network analysis was performed for all OTUs present in at least 30% of samples as recommended in (Berry and Widder, 2014) using graphical lasso technique cclasso to mitigate biases associated with compositional data (Danaher et al ., 2014). Network topological and node‐level properties were determined using the igraph package (Csardi, 2015) and networks were visualized using Cytoscape (Shannon et al ., 2003).…”

Rapid evolution of generalized resistance mechanisms can constrain the efficacy of phage–antibiotic treatments

“…Third, selection by phages and antibiotics could lead to increased costs of resistance, which could limit bacterial growth and infectiveness (Andersson & Hughes, 2010; Friman et al., 2016; Mumford & Friman, 2017). In support for this, it has been shown that phage selection can reduce P. aeruginosa and R. solanacearum growth and potential competitive ability most when bacteria evolved in the presence of both phage and antibiotics (Torres‐Barceló, Franzon, Vasse, & Hochberg, 2016; Wang et al., 2017), while phage resistance mutations have been shown to impair genes that are used for virulence leading to weaker infections (Addy, Askora, Kawasaki, Fujie, & Yamada, 2012; Chaturongakul & Ounjai, 2014; Torres‐Barceló et al., 2016). …”