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Infectious disease AND Urinary tract infection [keywords]
- Rapid identification of major Escherichia coli sequence types causing urinary tract and bloodstream infections. [JOURNAL ARTICLE]
- J Clin Microbiol 2014 Oct 29.
Escherichia coli sequence types (ST) 69, 73, 95 and 131 are collectively responsible for a large proportion of E. coli urinary tract and bloodstream infections, and differ markedly in their antibiotic susceptibility. We describe a novel PCR method to detect and distinguish these lineages rapidly. Three hundred and eighteen published E. coli genomes were compared, to identify signature sequences unique to each of the four major STs. The specificity of these sequences was assessed in silico by seeking them in an additional 98 genomes. A PCR assay was designed to amplify size-distinguishable fragments unique to the four lineages, and was validated using 515 E. coli isolates of known ST. Genome comparisons identified 22 regions, ranging in size from 335 bp to 26.5 kb, unique to one or other of the four predominant E. coli STs, with two to ten specific regions per ST. These regions predominantly harbored genes encoding hypothetical proteins and were within or adjacent to prophage sequences. Most (13/22) were highly conserved (>96.5% identity) in genomes of the respective ST. The new assay identified correctly all of 142 representatives of the four major STs in the validation set (n=515), with only two ST12 isolates misidentified as ST95. Compared with MLST, the assay thus had 100% sensitivity and 99.5% specificity. Rapid identification of major extra-intestinal E. coli STs will benefit future epidemiological studies and could be developed to tailor antibiotic therapy to the different susceptibilities of these dominant lineages.
- Pilicide ec240 Disrupts Virulence Circuits in Uropathogenic Escherichia coli. [Journal Article]
- MBio 2014; 5(6)
Chaperone-usher pathway (CUP) pili are extracellular organelles produced by Gram-negative bacteria that mediate bacterial pathogenesis. Small-molecule inhibitors of CUP pili, termed pilicides, were rationally designed and shown to inhibit type 1 or P piliation. Here, we show that pilicide ec240 decreased the levels of type 1, P, and S piliation. Transcriptomic and proteomic analyses using the cystitis isolate UTI89 revealed that ec240 dysregulated CUP pili and decreased motility. Paradoxically, the transcript levels of P and S pilus genes were increased during growth in ec240, even though the level of P and S piliation decreased. In contrast, the most downregulated transcripts after growth in ec240 were from the type 1 pilus genes. Type 1 pilus expression is controlled by inversion of the fimS promoter element, which can oscillate between phase on and phase off orientations. ec240 induced the fimS phase off orientation, and this effect was necessary for the majority of ec240's inhibition of type 1 piliation. ec240 increased levels of the transcriptional regulators SfaB and PapB, which were shown to induce the fimS promoter phase off orientation. Furthermore, the effect of ec240 on motility was abolished in the absence of the SfaB, PapB, SfaX, and PapX regulators. In contrast to the effects of ec240, deletion of the type 1 pilus operon led to increased S and P piliation and motility. Thus, ec240 dysregulated several uropathogenic Escherichia coli (UPEC) virulence factors through different mechanisms and independent of its effects on type 1 pilus biogenesis and may have potential as an antivirulence compound.CUP pili and flagella play active roles in the pathogenesis of a variety of Gram-negative bacterial infections, including urinary tract infections mediated by UPEC. These are extremely common infections that are often recurrent and increasingly caused by antibiotic-resistant organisms. Preventing piliation and motility through altered regulation and assembly of these important virulence factors could aid in the development of novel therapeutics. This study increases our understanding of the regulation of these virulence factors, providing new avenues by which to target their expression.
- Bacterial resistance to leucyl-tRNA synthetase inhibitor GSK2251052 develops during treatment of complicated urinary tract infections. [JOURNAL ARTICLE]
- Antimicrob Agents Chemother 2014 Oct 27.
GSK2251052, a novel leucyl-tRNA synthetase (LeuRS) inhibitor, was in development for the treatment of infections caused by multi-drug resistant Gram-negative pathogens. In a Phase II study (LRS114688) evaluating the efficacy of GSK2251052 in complicated urinary tract infections, resistance developed very rapidly in 3 of 14 subjects enrolled, with ≥32-fold increases in the GSK2251052 MIC of the infecting pathogen. A fourth subject did not exhibit development of resistance in the baseline pathogen, but did present with a different pathogen, resistant to GSK2251052, post-therapy. Whole genome DNA sequencing from E. coli isolates collected longitudinally from two LRS114688 subjects confirms that GSK2251052 resistance is due to specific mutations, selected on the first day of therapy, in the LeuRS editing domain. Phylogenetic analysis strongly suggests that resistant Escherichia coli isolates resulted from clonal expansion of baseline susceptible strains. This resistance development likely resulted from the confluence of multiple factors, of which only some can be assessed pre-clinically. Our study shows the challenges of developing antibiotics and the importance of clinical studies to evaluate their effect on disease pathogenesis.
- Draft Genome Assemblies of Proteus mirabilis ATCC 7002 and Proteus vulgaris ATCC 49132. [Journal Article]
- Genome Announc 2014; 2(5)
The pleomorphic swarming bacilli of the genus Proteus are common human gut commensal organisms but also the causative agents of recurrent urinary tract infections and bacteremia. We sequenced and assembled the 3.99-Mbp genome of Proteus mirabilis ATCC 7002 (accession no. JOVJ00000000) and the 3.97-Mbp genome of Proteus vulgaris ATCC 49132 (accession no. JPIX00000000), both of which are commonly used reference strains.
- Stenotrophomonas maltophilia Infection Among Young Children in a Cardiac Intensive Care Unit: A Single Institution Experience. [JOURNAL ARTICLE]
- Pediatr Cardiol 2014 Oct 8.
Stenotrophomonas maltophilia can present as bacteremia, respiratory tract infection, urinary tract infection, soft tissue and wound infections, bone and joint infections, meningitis, and endocarditis especially in immunosuppressed patients and those with underlying medical conditions. The incidence and impact of S. maltophilia in young children with heart disease are poorly defined. A single center retrospective observational study was conducted in infants <180 days of age with positive S. maltophilia cultures over a period of 5 years. The overall incidence for S. maltophilia infection was 0.8 % (n = 32/3656). Among 32 identified infants, there were 47 episodes of S. maltophilia infection 66 % of infants had prior exposure to broad spectrum antibiotics. 97 % of positive isolates were susceptible to trimethoprim/sulfamethoxazole and 91 % to levofloxacin as well as ticarcillin/clavulanate. Ventilator-free days and absolute lymphocyte count prior to acquiring infection were significantly lower in non-survivors than in survivors. 100 % of survivors had clearance of positive cultures compared to 50 % in non-survivors (p < 0.05). The crude all-cause mortality rate was 37.5 %. All non-survivors had increased length of ICU stay and duration of mechanical ventilation and had delayed clearance of infection and required longer duration of treatment.
- [Nosocomial infections in urology]. [English Abstract, Journal Article]
- Urologe A 2014 Oct; 53(10):1458-67.
Nosocomial infections (NI) may be a serious and mostly avoidable consequence of medical procedures and often cause a significant aggravation of the patients underlying disease. Following surgical site infections, urinary tract infections (UTI) represent the second most common fraction of NIs (22.4%) in Germany and contribute to approximately 155,000 nosocomial UTIs (nUTI) every year.Prevention of NI is of utmost individual as well as socioeconomic importance especially regarding the continuing worldwide increase in antibiotic resistance. National legislature has responded to this challenge by amending the German Law on the Prevention and Control of Infectious Diseases (IfSG) and other measures. Their practical importance for various clinical settings in urology is outlined in this overview.The correct use of urinary catheters has the greatest impact for prevention and control as nUTIs are associated with urinary catheters in most of the cases (80%). The recently updated guidelines of the Commission for Hospital Hygiene and Infection Prevention of the Robert Koch Institute (KRINKO) and the Association of the Scientific Medical Societies in Germany (AWMF) provide detailed recommendations in an evidence-based and practice-oriented manner as summarized in this article.
- Aerococcal Infection at Three US Tertiary Care Hospitals. [JOURNAL ARTICLE]
- South Med J 2014 Oct; 107(10):642-647.
The aim of the present study was to determine clinical features of Aerococcus infections and the significance of the Aerococcus species isolated from any clinical samples.Electronic records of all cultures yielding Aerococcus species from 2002 to 2012 were obtained from three tertiary care hospitals. We performed an in-depth review of medical records.Aerococcus was isolated from ≥1 site in 93 patients. Blood cultures were positive in 64 patients; 15 with definite bacteremia, including 3 with endocarditis, 7 with urinary tract infections, 13 with probable bacteremia, and 36 in which Aerococcus was judged to be a possible contaminant. Of 19 urine isolates, 10 were from patients with symptomatic urinary tract infections and 7 were from patients with asymptomatic bacteriuria; in 2 cases, urine isolates were regarded as possible contaminants. Most patients with urinary isolates had underlying urological abnormalities. Other sources for Aerococcus included synovial fluid, bile, bone, intraabdominal abscess, and ovarian abscess. All of the isolates tested with ampicillin, cefazolin, clindamycin, and vancomycin were susceptible. A total of two patients with definite Aerococcus infection died, but all of the others responded to antibiotic therapy.Aerococcus often is considered a contaminant; however, in our case series, 35% of cases in which Aerococcus was isolated from any site indicated a definite infection. In patients with positive blood cultures for Aerococcus, at least 23% were associated with infection. Appropriate attention needs to be directed to Aerococcus when it is isolated from a normally sterile site.
- Hospitalization before surgery increases risk for postoperative infections. [Journal Article]
- J Thorac Cardiovasc Surg 2014 Oct; 148(4):1615-1621.e3.
Exposure to a health care facility before surgery may increase risk for postoperative infections. Our objectives were to (1) determine whether the prevalence of postoperative infections was higher among patients who were hospitalized before cardiac surgery, (2) identify risk factors for infection, and (3) evaluate in-hospital outcomes.A total of 32,707 patients underwent cardiac surgery from January 1, 2000, to January 1, 2011. Forty percent (13,107) were hospitalized before their surgery date or were transfers from other health care facilities, and 60% (19,600) were same-day admissions. The primary outcome consisted of a composite infection: pneumonia, sepsis, surgical site infection, and urinary tract infection. The secondary outcome was in-hospital death. The propensity method was used to compare infectious complications and mortality between groups.Overall infectious complications occurred in 2327 patients (7.1%). Overall composite and individual infections decreased over the study period (P for trend <.0001). Among 7814 propensity-matched pairs, 522 infections (6.7%) occurred in the same-day admission group versus 676 (8.7%) in the prior hospitalization group, P < .0001. In-hospital mortality was 1.5% (n = 120) for the same-day admission group versus 2.8% (n = 221) for the prior hospitalization group (P < .0001).Although the risk of infection decreased over time, the relationship between exposure to a health care facility before surgical intervention and higher infection risk remained substantial. Further investigation into processes of care surrounding infection control is necessary to reduce postoperative infections and associated morbidity.
- An in vitro deletion in ribE encoding lumazine synthase contributes to nitrofurantoin resistance in Escherichia coli. [JOURNAL ARTICLE]
- Antimicrob Agents Chemother 2014 Sep 22.
Nitrofurantoin has been used for decades for the treatment of urinary tract infections (UTI), however, clinically significant resistance in E. coli is as yet uncommon. Nitrofurantoin concentrations in the gastrointestinal tract tend to be low, which might facilitate selection of nitrofurantoin-resistant (NIT-R) strains in the gut flora. We subjected two nitrofurantoin-susceptible intestinal E. coli strains (ST540-p, ST2747-p) to increasing nitrofurantoin concentrations under aerobic and anaerobic conditions. Whole genome sequencing was performed on both susceptible isolates and on selected mutants that exhibited the highest nitrofurantoin resistance levels aerobically (ST540-a, ST2747-a) and anaerobically (ST540-an, ST2747-an). ST540-a/-an and ST2747-a (aerobic MIC >64 μg/ml) harbored mutations in known nitrofurantoin resistance determinants, nfsA and/or nfsB that encode oxygen-insensitive nitroreductases. ST2747-an showed reduced nitrofurantoin susceptibility (aerobic MIC 32 μg/ml) and exhibited remarkable growth deficits, however, did not harbor nfsA/B mutations. We identified a 12-nucleotide deletion in ribE encoding lumazine synthase, an essential enzyme involved in the biosynthesis of FMN, an important cofactor of NfsA/B. Complementing ST2747-an with a functional wild-type lumazine synthase restored nitrofurantoin susceptibility. Six NIT-R E. coli (NRCI-1 to -6) isolated from stools of UTI patients treated with nitrofurantoin, cefuroxime, or a fluoroquinolone harbored mutations in nfsA and/or nfsB, but not in ribE. Sequencing of the ribE gene in six intestinal and three urinary E. coli strains showing reduced nitrofurantoin-susceptibility (MIC range 16-48 μg/ml) also did not identify any relevant mutations. NRCI-1, -2, -5 exhibited upto four-fold higher anaerobic MICs compared to the in vitro mutants, presumably because of additional mutations in oxygen-sensitive nitroreductases.
- The intimin-like protein FdeC is regulated by H-NS and temperature in Enterohaemorrhagic Escherichia coli. [JOURNAL ARTICLE]
- Appl Environ Microbiol 2014 Sep 19.
Enterohaemorrhagic Escherichia coli (EHEC) are Shiga toxigenic pathogens capable of inducing severe forms of enteritis (e.g. hemorrhagic colitis) and extraintestinal sequelae (e.g. hemolytic uremic syndrome). The molecular basis of colonization of human and animal hosts by EHEC is not yet completely understood and an improved understanding of EHEC mucosal adherence may lead to development of interventions that could disrupt host colonization. FdeC, also referred to by its IHE 3034 locus tag ECOK1_0290, is an intimin-like protein that was recently shown to contribute to kidney colonisation in a mouse urinary tract infection model. The expression of FdeC is tightly regulated in vitro, and FdeC shows promise as a vaccine candidate against extra-intestinal E. coli strains. In this study we characterised the prevalence, regulation and function of fdeC in EHEC. We showed that the fdeC gene is conserved in both O157 and non-O157 EHEC, and encodes a protein that is expressed at the cell surface and promotes biofilm formation under continuous flow conditions in a recombinant E. coli strain background. We also identified culture conditions where FdeC is expressed, and showed that minor alterations of these conditions, such as changes in temperature, can significantly alter the level of FdeC expression. Additionally, we demonstrate that the transcription of the fdeC gene is repressed by the global regulator H-NS. Taken together, our data suggest a role for FdeC in EHEC when growing at temperatures above 37°C, a condition relevant to its specialized niche at the recto-anal junction of cattle.