The vaginal microbiome is a complex and dynamic microecosystem that fluctuates continually throughout a woman's life. Lactobacillus, a bacterium that possesses antibacterial properties dominates a healthy vaginal microbiome. Bacterial vaginosis is the most common vaginal disorder that has been linked with the dysbiosis of normal vaginal microbiota. Despite the importance of vaginal microbiome, little is known about functions it performs especially, how it helps in protecting the female reproductive tract. This knowledge gap is a significant impediment to the development of effective and feasible clinical treatments that might be required to improve women's health. Thus, a deeper understanding of the functional aspects and not just the composition of vaginal microbiome may aid in improving the diagnostics and treatment strategies. Recent advancement in molecular methods and computational biology have allowed researchers to acquire more knowledge about the vaginal microbiome. The use of metagenomics (culture‐independent high‐throughput technology) and bioinformatics tools have improved our understanding of the vaginal microbiome. In this review, we have attempted to explore the factors that may alter normal vaginal microbiota homeostasis such as age, sexual behavior, ethnicity, and hygiene, and so forth. We also discuss the role of probiotics in restoring healthy vaginal microbiome.

Proteus mirabilis is a common cause of urinary tract infection, especially in catheterized individuals. Amino acids are the predominant nutrient for bacteria during growth in urine, and our prior studies identified several amino acid import and catabolism genes as fitness factors for P. mirabilis catheter‐associated urinary tract infection (CAUTI), particularly those for d‐ and l‐serine. In this study, we sought to determine the hierarchy of amino acid utilization by P. mirabilis and to examine the relative importance of d‐ vs l‐serine catabolism for critical steps in CAUTI development and progression. Herein, we show that P. mirabilis preferentially catabolizes l‐serine during growth in human urine, followed by d‐serine, threonine, tyrosine, glutamine, tryptophan, and phenylalanine. Independently disrupting catabolism of either d‐ or l‐serine has minimal impact on in vitro phenotypes while completely disrupting both pathways decreases motility, biofilm formation, and fitness due to perturbation of membrane potential and cell wall biosynthesis. In a mouse model of CAUTI, loss of either serine catabolism system decreased fitness, but disrupting l‐serine catabolism caused a greater fitness defect than disrupting d‐serine catabolism. We, therefore, conclude that the hierarchical utilization of amino acids may be a critical component of P. mirabilis colonization and pathogenesis within the urinary tract.

Proteus mirabilis is a common cause of urinary tract infection, especially in catheterized individuals. Amino acids are the predominant nutrient for bacteria during growth in urine, and our prior studies identified several amino acid import and catabolism genes as fitness factors for P. mirabilis catheter-associated urinary tract infection (CAUTI), particularly D- and L-serine. In this study, we sought to determine the hierarchy of amino acid utilization by P. mirabilis and to examine the relative importance of D- vs L-serine catabolism for critical steps in CAUTI development and progression. Herein, we show that P. mirabilis preferentially catabolizes L-serine during growth in human urine, followed by D-serine, threonine, tyrosine, glutamine, tryptophan, and phenylalanine. Independently disrupting catabolism of either D- or L-serine has minimal impact on in vitro phenotypes while completely disrupting both pathways decreases motility, biofilm formation, and fitness due to perturbation of membrane potential and cell wall biosynthesis. In a mouse model of CAUTI, loss of either serine catabolism system decreased fitness, but disrupting L-serine catabolism caused a greater fitness defect than disrupting D-serine catabolism. We therefore conclude that hierarchical utilization of amino acids may be a critical component of P. mirabilis colonization and pathogenesis within the urinary tract.

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