Experimental haematogenous pyelonephritis in mice with uropathogenic, enteropathogenic and enterotoxigenic

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...

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“…Quantitative bacterial counts (c.f.u.) were calculated (g kidney tissue) 21 , as reported by Kakar et al (1986).…”

Section: Therapeutic Effect Of Azm In Vivomentioning

confidence: 99%

“…Quantitative bacterial counts (c.f.u.) were calculated (g kidney tissue)21 , as reported by Kakar et al (1986).Histopathological examination. Kidney tissue from infected animals from all groups of mice was fixed in 10 % normal buffered saline and dehydrated in 30-100 % ethanol.…”

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confidence: 99%

Inhibition of quorum sensing in Pseudomonas aeruginosa by azithromycin and its effectiveness in urinary tract infections

Bala

Kumar

Harjai

2011

Journal of Medical Microbiology

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“…Aseptically, kidneys were weighed and homogenized in 1 mL sterile saline solution. Quantitative bacterial counts were calculated per gram of kidney tissue as reported by Kakkar et al (1986).…”

Section: Bacteriological Examinationmentioning

confidence: 99%

Garlic blocks quorum sensing and attenuates the virulence ofPseudomonas aeruginosa

Harjai

Kumar

Singh

2010

FEMS Immunol Med Microbiol

108

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Pseudomonas aeruginosa is an opportunistic pathogen that colonizes urinary catheters, forms biofilms, and is responsible for causing persistent and recurrent nosocomial catheter-associated urinary tract infections (UTIs). These infections show increased morbidity and mortality in immunocompromised patients. Quorum sensing in P. aeruginosa plays a key role in biofilm formation, virulence factor production and antimicrobial resistance. Because of emerging antimicrobial resistance in P. aeruginosa, there is a need to find an alternate nonantibiotic agent for the control of infections caused by this organism. In the present study, garlic was evaluated as a prophylactic agent in vivo in a mouse UTI model. Oral treatment with garlic significantly lowered renal bacterial counts and protected mouse kidney from tissue destruction. In vitro data showed decreased elaboration of virulence factors and reduced production of quorum-sensing signals by P. aeruginosa in the presence of fresh garlic extract. The results suggest that decreased virulence of P. aeruginosa in garlic-fed mice can be attributed to the quorum-sensing inhibitory property of garlic. This might have contributed towards reduced production of virulence factors, as seen in vitro.

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“…To determine the bacterial load in the spleen, mice were killed on different days post infection. Bacterial load was assayed by plating the 10-fold serially diluted tissue homogenate on deoxycholate citrate agar (DCA) and keeping it overnight at 37°C [20].…”

Section: Bacterial Loadmentioning

confidence: 99%

Effect of propolis extract on hematotoxicity and histological changes induced by Salmonella enterica serovar Typhimurium in BALB/c mice

Kalia

Kumar

Harjai

2016

ARCH BIOL SCI BELGRA

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Typhoid fever, a life-threatening disease, causes several pathological changes due to the involvement of one or more organs. In the present study, the effect of typhoid on hematological indices and spleen histology in infected mice were investigated. The ameliorative efficacy of the ethanolic extract of propolis was tested and compared with treatment with the typhoid drug,cefixime. BALB/c mice were divided into six groups: group1 was the normal control, group 2 was infected with Salmonella enteric serovar Typhimurium, group 3 was Salmonella infected and treated with cefixime, groups4 and 5 were Salmonella-infected mice treated with 100 mg and 300 mg of propolis respectively. Group 6 was given only 300 mg propolis without infection. Mice were killed after completion of treatment and examination of spleen histology and hematological studies were performed. Significant differences were observed in the propolis-treated group of mice as compared to the infected group without antibiotic, further confirming the ameliorative effect of propolis on Salmonella enterica serovar Typhimurium-induced toxicity in mice.

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Experimental haematogenous pyelonephritis in mice with uropathogenic, enteropathogenic and enterotoxigenic

Cited by 11 publications

References 13 publications

Inhibition of quorum sensing in Pseudomonas aeruginosa by azithromycin and its effectiveness in urinary tract infections

Inhibition of quorum sensing in Pseudomonas aeruginosa by azithromycin and its effectiveness in urinary tract infections

Garlic blocks quorum sensing and attenuates the virulence ofPseudomonas aeruginosa

Effect of propolis extract on hematotoxicity and histological changes induced by Salmonella enterica serovar Typhimurium in BALB/c mice

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