Urinary tract infections (UTIs) are a serious health problem affecting millions of people each year. Infections of the urinary tract are the second most common type of infection in the body. Catheterization of the urinary tract is the most common factor, which predisposes the host to these infections. Catheter-associated UTI (CAUTI) is responsible for 40% of nosocomial infections, making it the most common cause of nosocomial infection. CAUTI accounts for more than 1 million cases in hospitals and nursing homes annually and often involve uropathogens other than Escherichia coli. While the epidemiology and pathogenic mechanisms of uropathogenic Escherichia coli have been extensively studied, little is known about the pathogenesis of UTIs caused by other organisms like Pseudomonas aeruginosa. Scanty available information regarding pathogenesis of UTIs caused by P. aeruginosa is an important bottleneck in developing effective preventive approaches. The aim of this review is to summarize some of the advances made in the field of P. aeruginosa induced UTIs and draws attention of the workers that more basic research at the level of pathogenesis is needed so that novel strategies can be designed.

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Pseudomonas aeruginosa is an opportunistic pathogen and the leading cause of mortality among immunocompromised patients in clinical setups. The hallmarks of virulence in P. aeruginosa encompass six biologically competent attributes that cumulatively drive disease progression in a multistep manner. These multifaceted hallmarks lay the principal foundation for rationalizing the complexities of pseudomonal infections. They include factors for host colonization and bacterial motility, biofilm formation, production of destructive enzymes, toxic secondary metabolites, iron-chelating siderophores and toxins. This arsenal of virulence hallmarks is fostered and stringently regulated by the bacterial signalling system called quorum sensing (QS). The central regulatory functions of QS in controlling the timely expression of these virulence hallmarks for adaptation and survival drive the disease outcome. This review describes the intricate mechanisms of QS in P. aeruginosa and its role in shaping bacterial responses, boosting bacterial fitness. We summarize the virulence hallmarks of P. aeruginosa, relating them with the QS circuitry in clinical infections. We also examine the role of QS in the development of drug resistance and propose a novel antivirulence therapy to combat P. aeruginosa infections. This can prove to be a next-generation therapy that may eventually become refractory to the use of conventional antimicrobial treatments.

Characterization of bacteriophages to be used prophylactically or therapeutically is mandatory, as use of uncharacterized bacteriophages is considered as one of the major reasons of failure of phage therapy in preantibiotic era. In the present study, one lytic bacteriophage, KPO1K2, specific for Klebsiella pneumoniae B5055, with broad host range was selected for characterization. As shown by TEM, morphologically KPO1K2 possessed icosahedral head with pentagonal nature with apex to apex head diameter of about 39 nm. Presence of short noncontractile tail (10 nm) suggested its inclusion into family Podoviridae with a designation of T7-like lytic bacteriophage. The phage growth cycle with a latent period of 15 min and a burst size of approximately 140 plaque forming units per infected cell as well as a genome of 42 kbps and structural protein pattern of this bacteriophage further confirmed its T7-like characteristics. Phage was stable over a wide pH range of 4-11 and demonstrated maximum activity at 37 degrees C. After injection into mice, at 6 h, a high phage titer was seen in blood as well as in kidney and urinary bladder, though titers in kidney and urinary bladder were higher as compared to blood. Phage got cleared completely in 36 h from blood while from kidneys and urinary bladder its clearance was delayed. We propose the use of this characterized phage, KPO1K2, as a prophylactic/therapeutic agent especially for the treatment of catheter associated UTI caused by Klebsiella pneumoniae.

Pseudomonas aeruginosa, an opportunistic pathogen, is the third most common pathogen associated with nosocomial urinary tract infections (UTIs). The virulence of this organism is due to its ability to produce quorum-sensing (QS) signal molecules and form biofilms. These biofilms are usually resistant to conventional antibiotics and host immune responses. Recently, beneficial effects of macrolides, especially azithromycin (AZM), have been shown in patients suffering from chronic infections caused by P. aeruginosa. These were due to anti-inflammatory and modulatory effects of AZM on the expression of virulence factors of this pathogen. The present study was designed to evaluate the potential of AZM to inhibit QS signal molecules and its ability to attenuate the virulence of P. aeruginosa in an experimental UTI model. Sub-MIC concentrations of AZM significantly inhibited the production of QS signals, swimming, swarming and twitching motilities, and biofilm formation in vitro. The therapeutic evaluation of AZM in this experimental UTI model showed complete clearance of the organisms from the mouse kidneys. The results of this study highlight the potential effectiveness of AZM in attenuating the virulence of P. aeruginosa in a UTI model. INTRODUCTIONQuorum sensing (QS) is an important global gene regulatory mechanism in bacteria that enables individual bacteria to coordinate their behaviour in populations. The QS system relies on self-generated signalling molecules, which coordinate gene expression in response to population density (Rumbaugh et al., 2000). Many processes that assist in the survival, persistence and pathogenesis of Pseudomonas aeruginosa, such as the expression of virulence factors and biofilm formation, are under the control of QS. Two interrelated QS systems, las and rhl, have been reported in P. aeruginosa and act in a hierarchical manner (Davies et al., 1998;Favre-Bonté et al., 2003;de Kievit, 2009). Both systems consist of inducer and regulatory proteins and a cognate autoinducer signal molecule, N-(3-oxododecanoyl) homoserine lactone (OdDHL) and N-butanoyl homoserine lactone (BHL), respectively (Rumbaugh et al., 2000;Venturi, 2006). P. aeruginosa causes infections in a variety of situations, such as cystic fibrosis, burns, cancer and traumatic wounds, especially in immunocompromised hosts, and can be a problem in intensive care units (Van Delden & Iglewski, 1998;Singh et al., 2000;Ehrlich et al., 2002). It has a tendency to form biofilms on biotic and abiotic surfaces such as catheters and lead to persistent and chronic urinary tract infections (UTIs) (Donlan & Costerton, 2002;Willcox et al., 2008). These biofilms are usually resistant to antibiotics and host immune defence clearance, and hence are difficult to eradicate by antibiotic intervention (Ceri et al., 1999;Costerton et al., 1999;Donlan, 2001).Although antibiotic therapy has great benefits in treatment, the emergence of multidrug resistance in P. aeruginosa has left clinicians with limited therapeutic options. Azithromycin (AZM), a memb...