Abstract
Bacteriuria, the presence of bacteria in urine, is associated with asymptomatic, as well as symptomatic, urinary tract infection (UTI). Bacteriuria underpins some of the dynamics of microbial colonization of the urinary tract, and probably impacts the progression and persistence of infection in some individuals. Recent molecular discoveries in vitro have elucidated how some key bacterial traits can enable organisms to survive and grow in human urine as a means of microbial fitness adaptation for UTI. Several microbial characteristics that confer bacteruric potential have been identified including de novo synthesis of guanine, relative resistance to D-serine, and catabolism of malic acid. Microbial characteristics such as these are increasingly being defined through the use of synthetic human urine (SHU) in vitro as a model to mimic the in vivo environment that bacteria encounter in the bladder. There is considerable variation in the SHU model systems that have been used to study bacteriuria to date, and this influences the utility of these models. In this review, we discuss recent advances in our understanding of bacteruric potential with a focus on the specific mechanisms underlying traits that promote the growth of bacteria in urine. We also review the application of SHU in research studies modeling UTI and discuss the chemical makeup, and benefits and limitations that are encountered in utilizing SHU to study bacterial growth in urine in vitro.
Highlights
BACTERIURIA AND URINARY TRACT INFECTION “Asymptomatic Bacteriuria” (ABU or ASB) is synonymous with asymptomatic Urinary Tract Infection (UTI) in defining the isolation of a specified semi-quantitative count of bacteria in an appropriately collected urine specimen from a person without signs or symptoms related to UTI (Rubin et al, 1992; Nicolle et al, 2005)
We review the application of synthetic human urine (SHU) in research studies modeling UTI and discuss the chemical makeup, and benefits and limitations that are encountered in utilizing SHU to study bacterial growth in urine in vitro
To standardize SHU composition for bacteriuria studies, we propose a composite SHU medium recipe (Table 2), and compare this to descriptions of “typical human urine” (Putnam et al, 1971; Bouatra et al, 2013)
Summary
BACTERIURIA AND URINARY TRACT INFECTION “Asymptomatic Bacteriuria” (ABU or ASB) is synonymous with asymptomatic Urinary Tract Infection (UTI) in defining the isolation of a specified semi-quantitative count of bacteria in an appropriately collected urine specimen from a person without signs or symptoms related to UTI (Rubin et al, 1992; Nicolle et al, 2005). Antibiotics stop the progression of bacteriuria (Schneeberger et al, 2012) but patients infected with E. coli experience re-colonization with the same or similar organism at high rates (Dalal et al, 2009). Persistence of bacteriuria relates to microbial bacteruric potential and host characteristics/dynamics including genetic immunodeficiency, re-current infection or strain replacement, and antibiotic therapy. Analysis of ABU E. coli 83972 re-isolates indicated marked versatility of metabolic pathways in urine, including utilization of amino acids, hexuronates or (deoxy-) ribonucleosides as an adaptation to individual hosts (Zdziarski et al, 2010). This underlines the metabolic versatility of E. coli in urine in response to hostspecific metabolic constraints. The tricarboxylic acid cycle, and the glyoxylate shunt was highly variable, and likely caused by adaptive processes in individual strains during infection (Berger et al, 2014)
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