Pathogenesis of Proteus mirabilis Infection

Abstract

Proteus mirabilis, a Gram-negative rod-shaped bacterium most noted for its swarming motility and urease activity, frequently causes catheter-associated urinary tract infections (CAUTI) that are often polymicrobial. These infections may be accompanied by urolithiasis, development of bladder or kidney stones due to alkalinization of urine from urease-catalyzed urea hydrolysis. Adherence of the bacterium to epithelial and catheter surfaces is mediated by 17 different fimbriae, most notably MR/P fimbriae. Repressors of motility are often encoded by these fimbrial operons. Motility is mediated by flagella encoded on a single contiguous 54 kb chromosomal sequence. On agar plates, P. mirabilis undergoes a morphological conversion to a filamentous swarmer cell expressing hundreds of flagella. When swarms from different strains meet, a line of demarcation, a “Dienes line”, develops due to the killing action of each strain’s type VI secretion system. During infection, histological damage is caused by cytotoxins including hemolysin and a variety of proteases, some autotransported. The pathogenesis of infection, including assessment of individual genes or global screens for virulence or fitness factors has been assessed in murine models of ascending UTI or CAUTI using both single-species and polymicrobial models. Global gene expression studies carried out in culture and in the murine model have revealed the unique metabolism of this bacterium. Vaccines, using MR/P fimbria and its adhesin, MrpH, have been shown to be efficacious in the murine model. A comprehensive review of factors associated with urinary tract infection is presented, encompassing both historical perspectives and current advances.

A rare opportunist,Morganella morganii, decreases severity of polymicrobial catheter-associated urinary tract infection

“…Our experimental findings have important clinical implications, particularly for patient populations requiring long-term catheterization. Approximately 50% of individuals catheterized for 28 days or longer experience catheter blockage and/or encrustation from crystalline deposits, the vast majority of which are the result of P. mirabilis urease activity (10, 12, 56, 57). These crystalline deposits accumulate on the catheter surface and facilitate biofilm formation (58), a bacterial mode of growth that is associated with immune evasion and antimicrobial resistance (59).…”

Time‐Resolved Dynamics of Struvite Crystallization: Insights from the Macroscopic to Molecular Scale

“…The primary motivation for this study is derived from the dearth of information regarding the factors that mediate the formation of struvite infection stones in urolithiasis, which is one of the most difficult and dangerous stone diseases due to the large size and rapid growth of the crystals, and high recurrence rate . Infection by urease‐positive bacteria, predominantly Proteus mirabilis , leads to a cascade of reactions that elevate urinary pH, as well as ammonium and phosphate ion concentrations, thus resulting in struvite formation . Struvite crystals, without proper treatment, can develop into large staghorn calculi (>2500 mm 2 ), with the capacity to fill the entire intrarenal collecting system, irritating the bladder and blocking the flow of urine .…”

“…[14] Infection by urease-positive bacteria,p redominantly Proteusm irabilis,l eads to ac ascade of reactions that elevate urinaryp H, as well as ammonium and phosphate ion concentrations, thus resulting in struvitef ormation. [11,15,16] Struvite crystals, without propert reatment, can develop into large staghorn calculi (> 2500 mm 2 ), with the capacity to fill the entire intrarenal collecting system, irritating the bladder and blockingt he flow of urine. [17,18] Moreover,c rystallineb iofilms composed of struvitec omplicate the care of patients undergoing long-term catheterization due to catheter encrustationa nd blockage, which impacts approximately 50 %o fc atheter users.…”

Correlation of pathogenic factors with antimicrobial resistance of clinicalProteus mirabilisstrains

“…Following Escherichia coli and Klebsiella pneumoniae, Proteus mirabilis is the third most common etiological factor of the urinary tract infection (UTI) [1–5], being mainly responsible for complicated UTIs or UTIs in long-term catheterized patients. Furthermore, the ability of P. mirabilis to form apatite or/and struvite stones in bladder and kidney causes severe pain in patients, and augments therapeutic difficulties [3,6,7].…”

“…P. mirabilis carries genes of 17 distinct fimbrial structures, the most important being mannose-resistant Proteus -like pili (MR/P), P. mirabilis P-like pili (PMP), P. mirabilis fimbriae (PMF), ambient-temperature fimbriae (ATF) and uroepithelial cell adhesin (UCA) [2,8]. Other significant virulence factors include toxins (HpmAB), iron and zinc uptake systems, proteases and flagella [1,2,4], and urease which hydrolyses urea to ammonia and carbon dioxide. This activity is a substantial source of nitrogen for bacteria and also contributes to the formation of crystalline biofilm that blocks the catheter lumen which is considered one of the most important virulence factors of P. mirabilis [3,9–11].…”