Kidney Abscess Research Articles

The νSaα Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells.

All Staphylococcus aureus genomes contain a genomic island, which is termed νSaα and characterized by two clusters of tandem repeat sequences, i.e. the exotoxin (set) and 'lipoprotein-like' genes (lpl). Based on their structural similarities the νSaα islands have been classified as type I to IV. The genomes of highly pathogenic and particularly epidemic S. aureus strains (USA300, N315, Mu50, NCTC8325, Newman, COL, JH1 or JH9) belonging to the clonal complexes CC5 and CC8 bear a type I νSaα island. Since the contribution of the lpl gene cluster encoded in the νSaα island to virulence is unclear to date, we deleted the entire lpl gene cluster in S. aureus USA300. The results showed that the mutant was deficient in the stimulation of pro-inflammatory cytokines in human monocytes, macrophages and keratinocytes. Purified lipoprotein Lpl1 was further shown to elicit a TLR2-dependent response. Furthermore, heterologous expression of the USA300 lpl cluster in other S. aureus strains enhanced their immune stimulatory activity. Most importantly, the lpl cluster contributed to invasion of S. aureus into human keratinocytes and mouse skin and the non-invasive S. carnosus expressing the lpl gene cluster became invasive. Additionally, in a murine kidney abscess model the bacterial burden in the kidneys was higher in wild type than in mutant mice. In this infection model the lpl cluster, thus, contributes to virulence. The present report is one of the first studies addressing the role of the νSaα encoded lpl gene cluster in staphylococcal virulence. The finding that the lpl gene cluster contributes to internalization into non-professional antigen presenting cells such as keratinocytes highlights the lpl as a new cell surface component that triggers host cell invasion by S. aureus. Increased invasion in murine skin and an increased bacterial burden in a murine kidney abscess model suggest that the lpl gene cluster serves as an important virulence factor.

CTLA4 Immunoglobulin but Not Anti-Tumor Necrosis Factor Therapy Promotes Staphylococcal Septic Arthritis in Mice.

The development of biologics has greatly increased the quality of life and the life expectancy of many patients with rheumatoid arthritis. However, a large number of these patients have an increased risk of developing serious infections. The aim of this study was to examine differential effects of anti-tumor necrosis factor (TNF) treatment and CTLA4 immunoglobulin (Ig) treatment on both immunological response and host defense in a murine model of septic arthritis. Abatacept (CTLA4-Ig), etanercept (anti-TNF), or phosphate-buffered saline were given to NMRI mice intravenously inoculated with Staphylococcus aureus. The clinical course of septic arthritis and histopathological and radiological changes of joints were compared among the groups. Mice receiving CTLA4-Ig treatment had more-severe septic arthritis, compared with controls and mice receiving anti-TNF treatment. Anti-TNF treatment led to more-severe weight loss and kidney abscesses, as well as a higher bacterial burden in the kidneys. Mice receiving CTLA4-Ig therapy had lower serum levels of interleukin 4, whereas mice receiving anti-TNF therapy had higher levels of TNF-α. Both iNOS and arginase-1 expression were reduced in peritoneal macrophages from mice receiving CTLA4-Ig, compared with expression in the anti-TNF group. CTLA4-Ig therapy significantly increased the susceptibility to S. aureus septic arthritis in mice, whereas anti-TNF therapy deteriorated host bacterial clearance, resulting in more-severe weight loss and kidney abscesses.

Staphylococcus aureus β-toxin Production is Common in Strains With the β-toxin Gene Inactivated by Bacteriophage

Staphylococcus aureus causes life-threatening infections, including infective endocarditis, sepsis, and pneumonia. β-toxin is a sphingomyelinase encoded for by virtually all S. aureus strains and exhibits human immune cell cytotoxicity. The toxin enhances S. aureus phenol-soluble modulin activity, and its activity is enhanced by superantigens. The bacteriophage φSa3 inserts into the β-toxin gene in human strains, inactivating it in the majority of S. aureus clonal groups. Hence, most strains are reported not to secrete β-toxin. This dynamic was investigated by examining β-toxin production by multiple clonal groups of S. aureus, both in vitro and in vivo during infections in rabbit models of infective endocarditis, sepsis, and pneumonia. β-toxin phenotypic variants are common among strains containing φSa3. In vivo, φSa3 is differentially induced in heart vegetations, kidney abscesses, and ischemic liver compared to spleen and blood, and in vitro growth in liquid culture. Furthermore, in pneumonia, wild-type β-toxin production leads to development of large caseous lesions, and in infective endocarditis, increases the size of pathognomonic vegetations. This study demonstrates the dynamic interaction between S. aureus and the infected host, where φSa3 serves as a regulator of virulence gene expression, and increased fitness and virulence in new environments.

NOD2 is dispensable for ATG16L1 deficiency-mediated resistance to urinary tract infection

NOD2 (nucleotide-binding oligomerization domain containing 2) functions as a pathogen sensor and is involved in development of Crohn disease, a form of inflammatory bowel disease. NOD2 functions in concert with the autophagy protein ATG16L1, which is also implicated in Crohn disease. Recently, we identified a novel protective role of ATG16L1 deficiency in uropathogenic Escherichia coli-induced urinary tract infections (UTIs), which are common infectious diseases in humans. Given the known roles of NOD2 in recruiting ATG16L1 to the bacterial entry site, autophagy induction, and Crohn disease, we hypothesized that NOD2 may also play an important role in UTI pathogenesis. Instead, we found evidence that NOD2 is dispensable in the pathogenesis of UTIs in mice and humans. First, loss of Nod2 did not affect the clearance of bacteriuria and the recruitment of innate immune cells to the bladder. Second, we showed that, although nod2−/− mice display increased kidney abscesses in the upper urinary tract, there were no increased bacterial loads or persistence in this niche. Third, although a previous study indicates that loss of Nod2 reverses the protection from intestinal infection afforded by loss of ATG16L1 in mice, we found NOD2 deficiency did not reverse the ATG16L1-deficiency-induced protection from UTI. Finally, a population-based study of a cohort of 1819 patients did not reveal any association of NOD2 polymorphisms with UTI incidence. Together, our data indicated that NOD2 is dispensable for UTI pathogenesis in both mice and humans and does not contribute to ATG16L1-deficiency-induced resistance to UTI in mice.

Superantigens Are Critical for Staphylococcus aureus Infective Endocarditis, Sepsis, and Acute Kidney Injury

ABSTRACTInfective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs’ role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses.

Multiple metastatic infections in a hemodialysis patient with untunneled internal jugular catheter

We present an end-stage renal disease patient on dialysis with fever. The primary source was right internal jugular vein catheter which had metastatic infections in the body probably via an arteriovenous communication in a cavity in left lung. Patient had right psoas muscle abscess and a left kidney abscess. An (18) F-fluorodeoxyglucose-positron emission spectroscopy scan was done to find out left kidney abscess. A search of literature did not reveal many patients of psoas abscess secondary to infection of hemodialysis access.

Hypoxia-Inducible Factor 1-Regulated Lysyl Oxidase Is Involved in Staphylococcus aureus Abscess Formation

Hypoxia-inducible factor 1 (HIF-1) is the key transcription factor involved in the adaptation of mammals to hypoxia and plays a crucial role in cancer angiogenesis. Recent evidence suggests a leading role for HIF-1 in various inflammatory and infectious diseases. Here we describe the role of HIF-1 in Staphylococcus aureus infections by investigating the HIF-1-dependent host cell response. For this purpose, transcriptional profiling of HIF-1α-deficient HepG2 and control cells, both infected with Staphylococcus aureus, was performed. Four hours after infection, the expression of 190 genes, 24 of which were regulated via HIF-1, was influenced. LOX (encoding lysyl oxidase) was one of the upregulated genes with a potential impact on the course of S. aureus infection. LOX is an amine oxidase required for biosynthetic cross-linking of extracellular matrix components. LOX was upregulated in vitro in different cell cultures infected with S. aureus and also in vivo, in kidney abscesses of mice intravenously infected with S. aureus and in clinical skin samples from patients with S. aureus infections. Inhibition of LOX by β-aminopropionitrile (BAPN) did not affect the bacterial load in kidneys or blood but significantly influenced abscess morphology and collagenization. Our data provide evidence for a crucial role of HIF-1-regulated LOX in abscess formation.

Is the Pocket Ultrasound the “Phonendoscope” of the Urologist?

The objective was to evaluate the utility of the “pocket ultrasound” in making clinical decisions in urologic emergencies. From May to September 2011, 105 patients were assessed for urologic emergencies: acute flank pain, macroscopic hematuria, urinary retention, and lower urinary tract symptoms. All patients underwent an ultrasonographic examination whereby the pocket ultrasound was used to evaluate the kidneys and bladder, followed by another appropriate diagnostic test to verify the suggested diagnosis. Urinary retention was diagnosed in 10 patients. Of 48 subjects with hematuria, 34 had an immediate diagnosis: there were 18 cases of a bladder tumor, 13 cases of urolithiasis, and 2 cases of renal cell carcinoma; one ureteral stent was detected. Of 30 patients referred with lower urinary tract symptoms, 14 showed a high post micturition residual and 2 were seen to have bladder diverticula. Of 17 patients with acute flank pain, 1 had a kidney abscess, 5 had hydronephrosis, and 11 had urolithiasis. Ultrasonography provided a conclusive diagnosis in 67.6% of cases. Point-of-care pocket ultrasound allows a rapid diagnosis for treatment or triage of patients for appropriate referral to other diagnostic methods.

Kidney and Prostatic Abscesses Secondary to Burkholderia Cepacia: A Unique Constellation in an HIV-Positive Male

Kidney and Prostatic Abscesses Secondary to Burkholderia Cepacia: A Unique Constellation in an HIV-Positive Male

A case of septic pulmonary embolism caused by urinary tract infection

A 56-year-old woman with diabetes mellitus (DM) presented at our department with intermittent low-grade fever, right-side back pain and general fatigue, having taken antibiotics (cefotiam) for the preceding two weeks as prescribed at another healthcare facility. Despite the absence of any cough or sputum production, chest X-ray revealed multiple nodular lesions in the peripheral lung fi elds (Figure-1). These nodules were not observed at the time of initial treatment at the referring hospital. Chest CT indicated multiple nodules with necrotic centers in the peripheral bilateral lung fi elds (Figure-2). Abdominal CT showed a swollen right kidney and diffuse abscesses (Figure-3). A diagnosis of septic pulmonary embolism accompanied by pyelonephrosis was made. Accordingly, an alternative antibiotic (cefotaxime) was administered against sepsis. The multiple nodules in the lung and the diffuse renal abscesses simultaneously disappeared within two months after this course of highly potent anti-bacterial therapy. DM control was also accomplished by insulin therapy.Septic pulmonary embolism has been defi ned as a lung embolism caused by a blood clot infected with any of several bacterial or fungal species. Typically, patients present with high-grade fever, productive cough, general malaise and hemoptysis. The presence of DM has an unfavorable impact on disease progression and prognosis. The most common radiographic fi ndings are bilateral peripheral nodules with feeding vessels and cavity formations less than 3 cm in diameter (1). Septic pulmonary emboli are classifi ed according to their source, i.e.

CcpA Regulates Arginine Biosynthesis in Staphylococcus aureus through Repression of Proline Catabolism

Staphylococcus aureus is a leading cause of community-associated and nosocomial infections. Imperative to the success of S. aureus is the ability to adapt and utilize nutrients that are readily available. Genomic sequencing suggests that S. aureus has the genes required for synthesis of all twenty amino acids. However, in vitro experimentation demonstrates that staphylococci have multiple amino acid auxotrophies, including arginine. Although S. aureus possesses the highly conserved anabolic pathway that synthesizes arginine via glutamate, we demonstrate here that inactivation of ccpA facilitates the synthesis of arginine via the urea cycle utilizing proline as a substrate. Mutations within putA, rocD, arcB1, argG and argH abolished the ability of S. aureus JE2 ccpA::tetL to grow in the absence of arginine, whereas an interruption in argJBCF, arcB2, or proC had no effect. Furthermore, nuclear magnetic resonance demonstrated that JE2 ccpA::ermB produced 13C5 labeled arginine when grown with 13C5 proline. Taken together, these data support the conclusion that S. aureus synthesizes arginine from proline during growth on secondary carbon sources. Furthermore, although highly conserved in all sequenced S. aureus genomes, the arginine anabolic pathway (ArgJBCDFGH) is not functional under in vitro growth conditions. Finally, a mutation in argH attenuated virulence in a mouse kidney abscess model in comparison to wild type JE2 demonstrating the importance of arginine biosynthesis in vivo via the urea cycle. However, mutations in argB, argF, and putA did not attenuate virulence suggesting both the glutamate and proline pathways are active and they, or their pathway intermediates, can complement each other in vivo.

Vaccination With a UV-Irradiated Genetically Attenuated Mutant of Staphylococcus aureus Provides Protection Against Subsequent Systemic Infection

Staphylococcus aureus are gram-positive bacteria that cause clinically significant infections in humans. Severe S. aureus infections are particularly problematic in hospitalized patients and reoccur despite therapeutic measures. The absence of natural protective immune responses and the lack of high-throughput approaches to identify S. aureus antigens have imposed constraints in the development of effective vaccines. Here, we showed that vaccination with the genetically attenuated S. aureus mutant, inactivated using UV irradiation rather than heat, significantly increased survival and diminished bacterial burden and kidney abscesses when mice were challenged with virulent methicillin-sensitive or methicillin-resistant S. aureus. Protection conferred by immunization could be transferred to the naive host and was not observed in B-cell-deficient mice. Using a novel S. aureus whole-proteome microarray, we show that immunoglobulin G antibody responses to 83 proteins were observed in the immunized mice. These results suggest that protection against S. aureus infections requires antibody responses to the wide repertoire of antigens/virulence factors. Vaccination using UV-irradiated genetically attenuated S. aureus induces humoral immunity and provides a vaccine strategy for pathogens that fail to induce protective immunity. We also describe a novel, high-throughput technology to easily identify S. aureus antigens for vaccine development.

A privileged intraphagocyte niche is responsible for disseminated infection ofStaphylococcus aureusin a zebrafish model

The innate immune system is the primary defence against the versatile pathogen, Staphylococcus aureus. How this organism is able to avoid immune killing and cause infections is poorly understood. Using an established larval zebrafish infection model, we have shown that overwhelming infection is due to subversion of phagocytes by staphylococci, allowing bacteria to evade killing and found foci of disease. Larval zebrafish coinfected with two S. aureus strains carrying different fluorescent reporter gene fusions (but otherwise isogenic) had bacterial lesions, at the time of host death, containing predominantly one strain. Quantitative data using two marked strains revealed that the strain ratios, during overwhelming infection, were often skewed towards the extremes, with one strain predominating. Infection with passaged bacterial clones revealed the phenomenon not to bedue to adventitious mutations acquired by the pathogen. After infection of the host, all bacteria are internalized by phagocytes and the skewing of population ratios is absolutely dependent on the presence of phagocytes. Mathematical modelling of pathogen population dynamics revealed the data patterns are consistent with the hypothesis that a small number of infected phagocytes serve as an intracellular reservoir for S. aureus, which upon release leads to disseminated infection. Strategies to specifically alter neutrophil/macrophage numbers were used to map the potential subpopulation of phagocytes acting as a pathogen reservoir, revealing neutrophils as the likely ‘niche’. Subsequently in a murine sepsis model, S. aureus abscesses in kidneys were also found to be predominantly clonal, therefore likely founded by an individual cell, suggesting a potential mechanism analogous to the zebrafish model with few protected niches. These findings add credence to the argument that S. aureus control regimes should recognize both the intracellular as well as extracellular facets of the S. aureus life cycle.

Surgical management of stem cell transplantation‐related complications in children

HSCT is an established treatment option for some children with life-threatening diseases, but complications remain a major cause of morbidity and mortality. This retrospective data analysis addresses the surgical issues of children with HSCT-related complications. Between 2002 and 2008, HSCT was performed in 240 children for leukemias/lymphomas (n=135), solid tumors (n=59), immunodeficiencies (n=20), lipid storage diseases (n=10), autoimmune diseases (n=9), and others (n=7). HSCT-related complications requiring surgery occurred in 24 cases (10%) and most often in the leukemias/lymphomas group (18/24 cases): HC (cystoscopic irrigation, n=7), pulmonary aspergilloses (resection, n=7), bone necroses (core decompression, n=3), GvHD bowel (colostomy/PEG, n=2), ICH (drainage, n=2), bilateral kidney abscess (nephrectomies/renal transplantation, n=1), aspergillosis of the maxillary sinus (decompression, n=1), and post-traumatic wound healing disorder (meshed skin transplantation, n=1). Survival was 50% in the group with surgery and 62% in the group without (p=0.275). Even though this difference was not statistically significant, surgical intervention should be encouraged in all cases to achieve favorable results.

InvasiveKlebsiella pneumoniaeInfections, California, USA

Invasive<i>Klebsiella pneumoniae</i>Infections, California, USA

Renal abscess due to Aspergillus fumigatus as the only sign of disseminated aspergillosis in a patient with AIDS

Background Aspergillus fumigatus can cause a wide variety of clinical syndromes, especially in the three largest immunocompromised groups, such as HIV-infected patients. Primary renal aspergillosis is an extremely rare entity. Aims We report an unusual case of renal abscess due to Aspergillus fumigatus in a patient with AIDS. Methods We review clinical and laboratory records, and provide follow up of the patient. Results A 38-year-old man, HIV seropositive, was admitted to our hospital with fever, lumbar pain and respiratory symptoms. Abdominal ultrasound and computerised tomography showed a single and large lesion consistent with an abscess located in the left kidney. Aspergillus fumigatus was isolated from clinical sample obtained by ultrasound-guided needle aspiration. Despite a correct treatment based on amphotericin B and drainage of the abscess, surgery was necessary and nephrectomy was carried out. Histopathological examination of the surgical specimen confirmed the diagnosis of renal aspergillosis. Systemic antifungal therapy based on intravenous and oral voriconazole and highly active antiretroviral therapy was started after surgery. The patient had a good response to the established treatment and he remains in a good clinical condition at one year of follow up. Conclusions Combined medical and surgical treatment is the elective therapy for renal abscesses due to Aspergillus when percutaneous drainage and the administration of systemic antifungal drugs, such as amphotericin B and/or oral voriconazole or itraconazole, fail. This case emphasizes renal fungal infections should be included in the differential diagnosis of kidney abscesses in AIDS patients.

How staph thwarts attack

Staphylococcus aureus stifles its host's immune response by producing an immunosuppressive molecule, report [Thammavongsa and colleagues.][1] ![Figure][2] Staph infections caused fewer kidney abscesses (arrows) without adsA . The new study reveals that without the cell wall enzyme

1471: Focal Pyelonephritis- More Frecvent that we Think? Importance of Ultrasound Examination in Early Diagnosis

The incidence of renal abscess ranges from 1-10 cases per 10,000 hospital admissions. Spread of infection can affect the vital structures. Once infection spreads to the perinephric spaces, percutaneous or open surgical drainage is required. In our nephrology department, we had in 3 months 5 cases with clinical suspicion of kidney abscess diagnosed as focal pyelonephritis(FP), ultrasound (US) being the most important for the early diagnosis.

Role of the Twin-Arginine Translocation Pathway in Staphylococcus

In Staphylococcus, the twin-arginine translocation (Tat) pathway is present only in some species and is composed of TatA and TatC. The tatAC operon is associated with the fepABC operon, which encodes homologs to an iron-binding lipoprotein, an iron-dependent peroxidase (FepB), and a high-affinity iron permease. The FepB protein has a typical twin-arginine (RR) signal peptide. The tat and fep operons constitute an entity that is not present in all staphylococcal species. Our analysis was focused on Staphylococcus aureus and S. carnosus strains. Tat deletion mutants (DeltatatAC) were unable to export active FepB, indicating that this enzyme is a Tat substrate. When the RR signal sequence from FepB was fused to prolipase and protein A, their export became Tat dependent. Since no other protein with a Tat signal could be detected, the fepABC-tatAC genes comprise not only a genetic but also a functional unit. We demonstrated that FepABC drives iron import, and in a mouse kidney abscess model, the bacterial loads of DeltatatAC and Deltatat-fep mutants were decreased. For the first time, we show that the Tat pathway in S. aureus is functional and serves to translocate the iron-dependent peroxidase FepB.

High Grade Transitional Cell Carcinoma of the Renal Pelvis with Divergent Differentiation Mimicking a Renal Abscess

We describe an unusual case of high-grade transitional cell carcinoma of the renal pelvis with sarcomatoid and squamous differentiation that presented as a left renal abscess. The patient had originally been treated for minimally inva- sive transitional cell carcinoma of the urinary bladder and ureteral orifices five years prior. Computerized tomography scan findings were consistent with an abscess of the left kidney. Percutaneous nephrostomy with drainage afforded no clinical improvement. Nephrectomy was performed and tissue was removed piecemeal because of the diagnosis of an ab- scess. Macroscopically the tissue was fragmented and necrotic with patches of gray-tan abscess. Microscopic sections re- vealed a biphasic neoplasm with squamous and sarcomatous elements that were co-existent with evident morphologic transition. There was also evidence of residual papillary transitional cell carcinoma in the renal pelvis. The sarcomatoid component was immunoreactive for cytokeratin, and vimentin. A malignant process must always be considered as an un- derlying cause when patients present with an abscess especially when there is a prior history of malignancy.