MrpJ Directly Regulates Proteus mirabilis Virulence Factors, Including Fimbriae and Type VI Secretion, during Urinary Tract Infection

Abstract

is a leading cause of catheter-associated urinary tract infections (CAUTIs) and urolithiasis. The transcriptional regulator MrpJ inversely modulates two critical aspects of UTI progression: fimbria-mediated attachment and flagellum-mediated motility. Transcriptome data indicated a network of virulence-associated genes under MrpJ's control. Here, we identify the direct gene regulon of MrpJ and its contribution to pathogenesis, leading to the discovery of novel virulence targets. romatinmmunorecipitation followed by high-throughput uencing (ChIP-seq) was used for the first time in a CAUTI pathogen to probe for direct targets of MrpJ. Selected MrpJ-regulated genes were mutated and assessed for their contribution to UTI using a mouse model. ChIP-seq revealed a palindromic MrpJ binding sequence and 78 MrpJ-bound regions, including binding sites upstream of genes involved in motility, fimbriae, and a type VI secretion system (T6SS). A combinatorial mutation approach established the contribution of three fimbriae (, , and) to UTI and a new pathogenic role for the T6SS in UTI progression. In conclusion, this study (i) establishes the direct gene regulon and an MrpJ consensus binding site and (ii) led to the discovery of new virulence genes in UTI, which could be targeted for therapeutic intervention of CAUTI.

Relationship Between the Quorum Network (Sensing/Quenching) and Clinical Features of Pneumonia and Bacteraemia Caused by A. baumannii

“…In several pathogens, such as Yersinia pseudotuberculosis, Proteus mirabilis , and Vibrio cholerae , the QS system is the main regulatory mechanism of bacterial competence via T6SS, which is involved in the invasiveness and motility that favor the development of bacteraemia (Zhang et al, 2011; Debnath et al, 2018; Jaskólska et al, 2018; Trastoy et al, 2018). Moreover, in 86% of ICU patients, gastrointestinal tract colonization by a clinical strain of A. baumannii led to development of bacteraemia caused by genetically similar strains (Thom et al, 2010).…”

MrpH, a new class of metal-binding adhesin, requires zinc to mediate biofilm formation

“…mirabilis in mouse model experiments; this may be due to dysfunctional MR/P fimbrial production or assembly when mrpH is expressed from a plasmid, or, more likely, because the chromosomal mrpH mutation is polar on mrpJ . MrpJ is a transcriptional regulator that controls levels of multiple known and predicted virulence factors, including flagella, MR/P and other fimbriae, and a type VI secretion system [ 28 , 49 ]. Further study will be needed to tease apart the separate roles of MrpH and MrpJ during UTI.…”

“…mutation is polar on mrpJ. MrpJ is a transcriptional regulator that controls levels of multiple known and predicted virulence factors, including flagella, MR/P and other fimbriae, and a type VI secretion system [28,49]. Further study will be needed to tease apart the separate roles of MrpH and MrpJ during UTI.…”

From Welfare to Warfare: The Arbitration of Host-Microbiota Interplay by the Type VI Secretion System

“…Here, the presence of Proteus mirabilis and Klebsiella pneumoniae in this commensal community correlated with colitogenic potential (Garrett et al, 2010). Both of these species possess T6SSs that display antibacterial activity (Alteri et al, 2013;Hsieh et al, 2019), while this secretion system has also been shown to contribute to the fitness of the pathogens in vivo (Lery et al, 2014;Debnath et al, 2018). One can therefore contemplate a role for this secretion system in the TRUC model whereby T6SS-mediated elimination of commensal bacteria promotes an inflammatory response that cannot be restrained due to the immune genes deficiency of the host, resulting in colitis.…”