The Yersinia pestis HmsCDE regulatory system is essential for blockage of the oriental rat flea (Xenopsylla cheopis), a classic plague vector

Abstract

SUMMARY The second messenger molecule cyclic diguanylate (c-di-GMP) is essential for Y. pestis biofilm formation that is important for blockage-dependent plague transmission from fleas to mammals. Two diguanylate cyclases (DGCs) HmsT and Y3730 (HmsD) are responsible for biofilm formation in vitro and biofilm-dependent blockage in the oriental rat flea Xenopsylla cheopis, respectively. Here, we have identified a tripartite signaling system encoded by the y3729-y3731 operon that is responsible for regulation of biofilm formation in different environments. We present genetic evidence that a putative inner membrane-anchored protein with a large periplasmic domain Y3729 (HmsC) inhibits HmsD DGC activity in vitro while an outer membrane Pal-like putative lipoprotein Y3731 (HmsE) counteracts HmsC to activate HmsD in the gut of X. cheopis. We propose that HmsE is a critical element in transduction of environmental signal(s) required for HmsD-dependent biofilm formation.

The Disulfide Bonding System Suppresses CsgD-Independent Cellulose Production in Escherichia coli

“…yfiRNB are in a single operon in E. coli, and YfiR and YfiN have similar activities in E. coli as those in P. aeruginosa (51)(52)(53)59). Previous work has also shown that the YfiN homolog AwsR controls Pseudomonas fluorescens cellulose and biofilm formation (60), and in Yersinia pestis, the YfiN and YfiR homologs, HmsD and HmsC, respectively, contribute to biofilm formation and the blockage of blood intake in the rat flea Xenopsylla cheopis (61,62). The inhibition of YfiN by YfiR can be overcome in P. aeruginosa via overexpression of the outer membrane protein YfiB, which sequesters YfiR away from YfiN (53).…”

“…4A and B). In Y. pestis, biofilm formation was only modestly affected by deletion or overexpression of the YfiB homolog HmsE (61,62). In UPEC strain CFT073, yfiR deletion leads to an increase in cellulose and curli production along with attenuation of bladder and kidney titers in a murine urinary tract infection (UTI) model (52).…”

Diguanylate cyclase DgcP is involved in plant and human Pseudomonas spp. infections

“…The role of c‐di‐GMP in pathogenesis has been extensively studied in a number of animal and human bacterial pathogens, including Salmonella enterica (Hisert et al ., ; Lamprokostopoulou et al ., ), Vibrio cholerae (Tischler and Camilli, ), Yersinia pestis (Bobrov et al ., 2011; 2014) and P. aeruginosa (Kulasakara et al ., ; Ryan et al ., ; Li et al ., ). Pseudomonas aeruginosa is a versatile Gram‐negative bacterium that can be found in various environments, including soil, water and vegetation (Lyczak et al ., ).…”

Human Parasites in Medieval Europe

“…It is thought that when the rats die from plague infection their hungry fleas have little choice but to feed from humans, and this spreads the disease (Schotthoefer et al, 2011;Chouikha and Hinnebusch, 2012;Bobrov et al, 2014). The Black Death was the second pandemic of bubonic plague, and swept across medieval Europe from 1348 to 1352.…”