Vaccination approaches for the prevention of urinary tract infection

Urinary tract infections (UTIs) are one of the most common infectious diseases of humans, with approximately 150 million cases estimated to occur globally every year. UTIs usually start as a bladder infection (cystitis), but can develop into acute kidney infection (pyelonephritis) and even infection of the bloodstream (urosepsis). The high frequency of UTIs in community and nosocomial settings places an enormous burden on healthcare systems worldwide. Multiple different pathogens cause UTI, with uropathogenic E. coli (UPEC) the most common etiological agent. UTIs caused by these pathogens are increasingly associated with antibiotic resistance, thus severely reducing treatment options and significantly increasing UTI-associated morbidity and mortality. In this review we present an overview of the recent advances in vaccine research targeted towards the prevention of UPEC-mediated UTI. In the context of multidrug resistance, we conclude that vaccination represents a viable approach for the prevention of chronic and recurrent UTI

Changes in the structure of a Posidonia oceanica meadow and in the diversity of associated decapod, mollusc and echinoderm assemblages, resulting from inputs of waste from a marine fish farm (Malta, Central Mediterranean)

Nutrient inputs resulting from fish farming activities located in the vicinity of seagrass meadows can potentially alter the structure and affect the functioning of these ecosystems, however, few studies have addressed this problem. The impact of waste generated by an offshore fish farm in Malta (Central Mediterranean) on the structure of a meadow of the seagrass Posidonia oceanica and on the associated decapod, echinoderm and mollusc assemblages was studied by collecting samples from stations located at distances of 10 m, 30 m, 50 m, 90 m, 170 m and 330 m away from the farm. Meadow morphology and leaf epiphyte load changed with distance from the fish cages, as did the species richness and abundance of macroinvertebrates associated with the seagrass. However, while shoot morphometric measures increased significantly in value over the whole length of the transect (330 m), macroinvertebrate species richness and abundance peaked at an intermediate distance (40–160 m) from the cages. These results suggest that while waste generated from fish farms can severely alter the structure of a seagrass meadow over a large area, nutrient enrichment could increase productivity in certain parts of the same meadow, leading to a localized increase in species richness and abundance of associated macroinvertebrates. These changes result in different 'ecological zones' round the source of nutrient input.peer-reviewe

Functional heterogeneity of the UpaH autotransporter protein from uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) are responsible for the majority of urinary tract infections(UTI). To cause UTI, UPEC must adhere to epithelial cells of the urinary tract and overcome the shear flow forces of urine. This function is primarily mediated by fimbrial adhesins, which mediate specific attachment to host cell receptors. Another group of adhesins that contribute to UPEC mediated UTI are autotransporter (AT) proteins. AT proteins possess a range of virulence properties such as adherence, aggregation, invasion and biofilm formation. One recently characterized AT protein of UPEC is UpaH, a large AIDA-I type AT protein that contributes to biofilm formation and bladder colonization. In this study, we have characterized a series of naturally occurring variants of UpaH. We demonstrate that extensive sequence variation exists within the passenger-encoding domain of UpaH variants from different UPEC strains. This sequence variation is associated with functional heterogeneity with respect to the ability of UpaH to mediate biofilm formation. In contrast, all of the UpaH variants examined retained a conserved ability to mediate binding to extracellular matrix (ECM) proteins. Bioinformatic analysis of the UpaH passenger domain identified a conserved region (UpaHCR) and hydrophobic region (UpaHHR). Deletion of these domains reduced biofilm formation but not binding to ECM proteins. Despite variation in upaH sequence, the transcription of upaH was repressed by a conserved mechanism involving the global regulator H-NS, and mutation of the hns gene relieved this repression. Overall, our findings shed new light on the regulation and function of the UpaH AT protein

Uropathogenic Escherichia coli virulence and innate immune responses during urinary tract infection

Urinary tract infections (UTI) are among the most common infectious diseases of humans and are the most common nosocomial infections in the developed world. It is estimated that 40-50% of women and 5% of men will develop a UTI in their lifetime, and UTI accounts for more than 1 million hospitalizations and $1.6 billion in medical expenses each year in the USA. Uropathogenic Escherichia coli (UPEC) is the primary cause of UTI. This review presents an overview of recent discoveries related to the primary virulence factors of UPEC and major innate immune responses to infection of the lower urinary tract. New and emerging themes in UPEC research are discussed in the context of the interface between host and pathogen

Identification of genes important for growth of asymptomatic Bacteriuria Escherichia coli in urine

Escherichia coli is the most important etiological agent of urinary tract infections (UTIs). Unlike uropathogenic E. coli, which causes symptomatic infections, asymptomatic bacteriuria (ABU) E. coli strains typically lack essential virulence factors and colonize the bladder in the absence of symptoms. While ABU E. coli can persist in the bladder for long periods of time, little is known about the genetic determinants required for its growth and fitness in urine. To identify such genes, we have employed a transposon mutagenesis approach using the prototypic ABU E. coli strain 83972 and the clinical ABU E. coli strain VR89. Six genes involved in the biosynthesis of various amino acids and nucleobases were identified (carB, argE, argC, purA, metE, and ilvC), and site-specific mutants were subsequently constructed in E. coli 83972 and E. coli VR89 for each of these genes. In all cases, these mutants exhibited reduced growth rates and final cell densities in human urine. The growth defects could be complemented in trans as well as by supplementation with the appropriate amino acid or nucleobase. When assessed in vivo in a mouse model, E. coli 83972carAB and 83972argC showed a significantly reduced competitive advantage in the bladder and/or kidney during coinoculation experiments with the parent strain, whereas 83972metE and 83972ilvC did not. Taken together, our data have identified several biosynthesis pathways as new important fitness factors associated with the growth of ABU E. coli in human urine

Molecular characterization of endocarditis-associated Staphylococcus aureus

Infective endocarditis (IE) is a life-threatening infection of the heart endothelium and valves. Staphylococcus aureus is a predominant cause of severe IE and is frequently associated with infections in health care settings and device-related infections. Multilocus sequence typing (MLST), spa typing, and virulence gene microarrays are frequently used to classify S. aureus clinical isolates. This study examined the utility of these typing tools to investigate S. aureus epidemiology associated with IE. Ninety-seven S. aureus isolates were collected from patients diagnosed with (i) IE, (ii) bloodstream infection related to medical devices, (iii) bloodstream infection not related to medical devices, and (iv) skin or soft-tissue infections. The MLST clonal complex (CC) for each isolate was determined and compared to the CCs of members of the S. aureus population by eBURST analysis. The spa type of all isolates was also determined. A null model was used to determine correlations of IE with CC and spa type. DNA microarray analysis was performed, and a permutational analysis of multivariate variance (PERMANOVA) and principal coordinates analysis were conducted to identify genotypic differences between IE and non-IE strains. CC12, CC20, and spa type t160 were significantly associated with IE S. aureus. A subset of virulence-associated genes and alleles, including genes encoding staphylococcal superantigen-like proteins, fibrinogen-binding protein, and a leukocidin subunit, also significantly correlated with IE isolates. MLST, spa typing, and microarray analysis are promising tools for monitoring S. aureus epidemiology associated with IE. Further research to determine a role for the S. aureus IE-associated virulence genes identified in this study is warranted