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Prevention of catheter-associated urinary tract infection (CAUTI) over long-term usage of urinary catheters remains a great challenge. Bacterial interference using nonpathogenic bacteria, such as E...

Nasal carriage of Staphylococcus aureus is a risk factor for infection, but it is not yet understood why some individuals carry nasal S. aureus persistently, intermittently, or seemingly not at all when tested via culture methods. This study compared the nasal microbiomes of established S. aureus carriers and noncarriers, identified species associated with noncarriage, and tested them for anti-S. aureus activity using assays developed to model the nutrient-limited nasal mucosa., Staphylococcus aureus nasal carriage provides the bacterial reservoir for opportunistic infection. In comparing the nasal microbiomes of culture-defined persistent S. aureus carriers versus noncarriers, we detected S. aureus DNA in all noses, including those with an established history of S. aureus negativity based on culture. Colonization with Gammaproteobacteria, including Klebsiella aerogenes, Citrobacter koseri, Moraxella lincolnii, and select Acinetobacter spp., was associated with S. aureus noncarriage. We next developed physiological competition assays for testing anti-S. aureus activity of isolated nasal species, utilizing medium modeling the nutrient-limited fluid of the nasal mucosa, polarized primary nasal epithelia, and nasal secretions. K. aerogenes from the nose of an S. aureus noncarrier demonstrated >99% inhibition of S. aureus recovery in all assays, even when S. aureus was coincubated in 9-fold excess. Secreted S. aureus inhibitory proteins from K. aerogenes and M. lincolnii were heat-stable and

Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen and often colonizes pigs. To lower the risk of MRSA transmission to humans, a reduction of MRSA prevalence and/or load in pig farms is needed. The nasal microbiome contains commensal species that may protect against MRSA colonization and may be used to develop competitive exclusion strategies. To obtain a comprehensive understanding of the species that compete with MRSA in the developing porcine nasal microbiome, and the moment of MRSA colonization, we analyzed nasal swabs from piglets in two litters. The swabs were taken longitudinally, starting directly after birth until 6 weeks. Both 16S rRNA and tuf gene sequencing data with different phylogenetic resolutions and complementary culture-based and quantitative real-time PCR (qPCR)-based MRSA quantification data were collected. We employed a compositionally aware bioinformatics approach (CoDaSeq + rmcorr) for analysis of longitudinal measurements of the nasal microbiota. The richness and diversity in the developing nasal microbiota increased over time, albeit with a reduction of Firmicutes and Actinobacteria, and an increase of Proteobacteria. Coabundant groups (CAGs) of species showing strong positive and negative correlation with colonization of MRSA and S. aureus were identified. Combining 16S rRNA and tuf gene sequencing provided greater Staphylococcus species resolution, which is necessary to inform strategies with potential protective effects against MRSA colonization in pigs. IMPORTANCE The large reservoir of methicillin-resistant Staphylococcus aureus (MRSA) in pig farms imposes a significant zoonotic risk. An effective strategy to reduce MRSA colonization in pig farms is competitive exclusion whereby MRSA colonization can be reduced by the action of competing bacterial species. We complemented 16S rRNA gene sequencing with Staphylococcus-specific tuf gene sequencing to identify species anticorrelating with MRSA colonization. This approach allowed us to elucidate microbiome dynamics and identify species that are negatively and positively associated with MRSA, potentially suggesting a route for its competitive exclusion.

Our goal was to identify evidenced-based strategies to prevent and treat patients with neurogenic bladder who suffer from recurrent urinary tract infections. We focused on therapy beyond standard antibiotics to address a multitude of factors implicated in these complex infections. Anatomic and functional components specific to neurogenic bladder contribute to the risk of infection and require close clinical monitoring. The host-pathogen interaction is one that allows for colonization of bacteria in the bladder. We recognize that bacteriuria in the neurogenic bladder population does not equate with infection. Local antibiotic treatment and oral supplements are often not adequate to eliminate infection nor prevent recurrent infection due to biofilms. However, novel medical therapies, such as photodynamic therapy, bacterial interference, and infrared laser therapy to augment local immune cells, are promising options to prevent and treat symptomatic infection. A combination approach including management of anatomic and functional factors with medical intervention can significantly improve frequency of urinary infection. Further study of non-antibiotic therapeutic strategies is much needed as we recognize the complexity of the urinary biomes and the limitations of antibiotic therapies.

Resume Contexte Les infections urinaires sont un probleme majeur de sante publique chez les patients ayant une vessie neurologique. Premiere cause de morbidite et deuxieme de mortalite, leur frequence genere une consommation de soin importante, et entrainent une exposition antibiotique massive conduisant a une prevalence elevee de bacteries multiresistantes. Les strategies preventives non antibiotiques sont essentielles. L’interference bacterienne consiste en l’inoculation intra-vesicale de bacteries non pathogene afin de prevenir les infections urinaires symptomatiques. Objectif Revue systematique de la litterature des donnees cliniques humaines disponibles sur l’interference bacterienne dans la prevention des infections urinaires chez le patient avec vessie neurologique selon la methodologie PRISMA. Resultats Au total 7 etudes ont ete selectionnees. Malgre des effectifs reduits et des populations heterogenes : mode mictionnel variable, antecedents d’infections urinaires differents, protocoles d’inoculation variables, durees de suivis et criteres d’evaluation heterogenes, l’interference bacterienne semble efficace dans la prevention des infections urinaires avec une bonne tolerance et quasi-absence d’effets indesirables. Les limites sont la difficulte a realiser l’inoculation et son faible rendement qui represente un cout medico-economique. Conclusion Les etudes, malgre leur heterogeneite, ont mis en evidence l’efficacite de l’interference bacterienne sur la diminution des infections urinaires symptomatiques. Elles ont egalement montre l’absence d’effet secondaire deletere et la faisabilite de l’inoculation intra-vesicale d’une souche non pathogene d’Escherichia coli 83972 ou HU2117 dans une population avec vessie neurologique. Alternative prometteuse, mais de nombreux developpements sont necessaires pour rendre cette technique plus accessible en pratique quotidienne et assurer son efficacite au long cours.

Biofilm formation is a well organised, genetically-driven process, well characterized for numerous bacterial species which plays important role in urinary tract infections (UTIs). Adherence is a key event initiating each step in UTI pathogenesis. Such UTIs are difficult to treat owing to increased drug resistance within the biofilm cells. The review is mainly focused on biofilm-growing microorganisms because this form of growth poses a threat to chronically infected or immunocompromised patients and is difficult to eradicate from medical devices. Biofim formation process and mechanisms to its increased resistance to various antimicrobials is also discussed together with newer prophylactic and therapeutic approaches like catheters coated with hydrogels or antibiotics, nanoparticles, ionotrophoresis, biofilm enzyme inhibitors, liposomes, bacterial interference, bacteriophages, quorum sensing inhibitor, combining antimicrobial photodynamic therapy and antiadhesion agents. The review justifies the need for new antibiofilm drug. Key words: Biofilm, uropathogens, catheter, urinary tract infection, catheter-associated UTI (CAUTI).

Asymptomatic bacterial colonization of the urinary bladder (asymptomatic bacteriuria, ABU) can prevent bladder colonization by uropathogens and thus symptomatic urinary tract infection (UTI). Deliberate bladder colonization with Escherichia coli ABU isolate 83972 has been shown to outcompete uropathogens and prevent symptomatic UTI by bacterial interference. Many ABU isolates evolved from uropathogenic ancestors and, although attenuated, may still be able to express virulence-associated factors. Our aim was to screen for efficient and safe candidate strains that could be used as alternatives to E. coli 83972 for preventive and therapeutic bladder colonization. To identify ABU E. coli strains with minimal virulence potential but maximal interference efficiency, we compared nine ABU isolates from diabetic patients regarding their virulence- and fitness-associated phenotypes in vitro, their virulence in a murine model of sepsis and their genome content. We identified strains in competitive growth experiments, which successfully interfere with colonization of ABU isolate 83972 or uropathogenic E. coli strain 536. Six isolates were able to outcompete E. coli 83972 and two of them also outcompeted UPEC 536 during growth in urine. Superior competitiveness was not simply a result of better growth abilities in urine, but seems also to involve expression of antagonistic factors. Competitiveness in urine did not correlate with the prevalence of determinants coding for adhesins, iron uptake, toxins, and antagonistic factors. Three ABU strains (isolates 61, 106, and 123) with superior competitiveness relative to ABU model strain 83972 display low in vivo virulence in a murine sepsis model, and susceptibility to antibiotics. They belong to different phylogroups and differ in the presence of ExPEC virulence- and fitness-associated genes. Importantly, they all lack marked cytotoxic activity and exhibit a high LD50 value in the sepsis model. These strains represent promising candidates for a more detailed assessment of relevant fitness traits in urine and their suitability for therapeutic bladder colonization.

Otitis media with effusion (OME) is a biofilm driven disease and commonly accepted otopathogens, such as Haemophilus influenzae, Streptococcus pneumonia, and Moraxella catarrhalis, have been demonstrated to form polymicrobial biofilms within the middle ear cleft. However, Alloiococcus otitidis (A. otitidis), which is one of the most commonly found bacteria within middle ear aspirates of children with OME, has not been described to form biofilms. The aim of this study was to investigate whether A. otitidis can form biofilms and investigate the impact on antibiotic susceptibility and survivability in polymicrobial biofilms with H. influenzae in vitro. The ability of A. otitidis to form single-species and polymicrobial biofilms with H. influenzae was explored. Clinical and commercial strains of A. otitidis and H. influenzae were incubated in brain heart infusion with and without supplementation. Biofilm was imaged using confocal laser scanning microscopy and scanning electron microscopy. Quantification of biofilm biomass and viable bacterial number was assessed using crystal violet assays and viable cell counting in both optimal growth conditions and in adverse growth conditions (depleted media and sub-optimal growth temperature). Antimicrobial susceptibility and changes in antibiotic resistance of single-species and multi-species co-culture were assessed using a microdilution method to assess minimal bactericidal concentration and E-test for amoxicillin and ciprofloxacin. A. otitidis formed single-species and polymicrobial biofilms with H. influenzae. Additionally, whilst strain dependent, combinations of polymicrobial biofilms decreased antimicrobial susceptibility, albeit a small magnitude, in both planktonic and polymicrobial biofilms. Moreover, A. otitidis promoted H. influenzae survival by increasing biofilm production in depleted media and at suboptimal growth temperature. Our findings suggest that A. otitidis may play an indirect pathogenic role in otitis media by altering H. influenzae antibiotic susceptibility and enhancing growth under adverse conditions.

Urinary tract infection is a common problem among patients with neurogenic bladder dysfunction that can be costly and challenging to manage. Current literature on the topic of preventing urinary tract infections in this heterogeneous patient population is challenged by the difficulty in defining urinary tract infections and by the lack of long-term data from controlled randomized studies. New research suggests that intradetrusor injection of onabotulinumtoxin A may be a useful adjunct in preventing urinary tract infections, and further studies are needed to determine if probiotics, bacterial interference, and/or vaccines will prove to be of use in the population.

Urinary tract infections (UTIs) are the most common nosocomial infections, accounting for 40% of all nosocomial infections. As much as 80% of these infections are associated with the use of urinary catheters. The risk of developing catheter-associated UTI increases with each day of catheterization. The pathogenesis of catheter-associated UTI is related to susceptibility of inert catheter material to microbial colonization. Once firmly attached on the catheter surface or the uroepithelium, bacteria begin to change phenotypically, moving into the sessile, biofilm mode of growth. Bacterial interference or using nonpathogenic bacteria to prevent symptomatic infection may offer a solution to the problem of recurrent UTI in chronically catheterized individuals.

We study the differences between Pseudomonas aeruginosa from an infected wound (clinical strain) and a colony isolated from it. We assessed the in vitro inhibition of these P. aeruginosa biofilms by DNase and filtrate of Lactobacillus plantarum cultures (acid = AF and neutralize = NF) with crystal violet technique. Inhibition by AF was greatest than DNase for clinical and isolated strain (p

Study Design Non-randomized pilot trial Objectives Determine whether Escherichia coli 83972-coated urinary catheters in persons with spinal cord injury (SCI) practicing an intermittent catheterization program (ICP) could (1) achieve bladder colonization with this benign organism, and (2) decrease the rate of symptomatic urinary tract infection (UTI). Setting Outpatient SCI clinic in a Veterans Affairs hospital (USA) Methods Participants had neurogenic bladders secondary to SCI, were practicing ICP, had experienced at least 1 UTI, and had documented bacteruria within the past year. All subjects received a urinary catheter that had been pre-inoculated with E. coli 83972. The catheter was left in place for 3 days then removed. Subjects were followed with urine cultures and telephone calls weekly for 28 days and then monthly until E. coli 83972 was lost from the urine. Outcome measures were (1) the rate of successful bladder colonization, defined as the detection (≥102 cfu/ml) of E. coli 83972 in urine cultures for > 3 days after catheter removal and (2) the rate of symptomatic UTI while colonized with E. coli 83972. Results Thirteen subjects underwent 19 insertions of study catheters. Eight subjects (62%) became successfully colonized for > 3 days after catheter removal. In these 8 subjects, the rate of UTI while colonized was 0.77 per patient-year, in comparison to the rate of 2.27 UTI per patient-year prior to enrollment. Conclusions E. coli 83972-coated urinary catheters are a viable means to achieve bladder colonization with this potentially protective strain in persons practicing ICP.

Rationale: The relatively sparse but diverse microbiome in human lungs may become less diverse in chronic obstructive pulmonary disease (COPD). This article examines the relationship of this microbiome to emphysematous tissue destruction, number of terminal bronchioles, infiltrating inflammatory cells, and host gene expression.

Summary Objective The objective of this study was to define the nasal microbiome of hospital inpatients who are persistently colonized with methicillin-resistant Staphylococcus aureus (MRSA) compared with matched, non-colonized controls. Methods Twenty-six persistently MRSA-colonized subjects and 26 matched non-colonized controls were selected from the screening records of the infection control program at the Department of the Veteran Affairs Eastern Colorado Health Care System (VA-ECHCS). The nasal microbiotas were analyzed with PCR amplification and sequencing of the 16S ribosomal RNA (rRNA) gene. Comparison of all variables across the groups was performed using stratified logistic regression to account for the one-to-one matching. Canonical discriminant analysis was performed to assess differences in bacterial community across the two groups. Competing organisms were cocultured with MRSA in vitro. Results There was a negative association between MRSA colonization and colonization with Streptococcus spp. At the species level, multivariate analysis demonstrated a statistically significant negative association between colonization with Streptococcus mitis or Lactobacillus gasseri and MRSA. Coculture experiments revealed in vitro competition between S. mitis and all of the 22 MRSA strains isolated from subjects. Competition was blocked by addition of catalase to the media. Persistently colonized subjects had lesser microbial diversity than the non-colonized controls. Conclusion In a high-risk inpatient setting, bacterial competition in the nasal niche protects some patients from MRSA colonization.

Summary Background Patients with long-term indwelling catheters are at high risk of catheter-associated urinary tract infection (CAUTI). We hypothesized that colonizing the bladder with a benign Escherichia coli strain ( E. coli HU2117, a derivative of E. coli 83972) would prevent CAUTI in older, catheterized adults. Materials and methods Adults with chronic, indwelling urinary catheters received study catheters that had been pre-coated with E. coli HU2117. We monitored the cultivatable organisms in the bladder for 28 days or until loss of E. coli HU2117. Urine from 4 subjects was collected longitudinally for 16S rRNA gene profiling. Results Eight of the ten subjects (average age 70.9 years) became colonized with E. coli HU2117, with a mean duration of 57.7 days (median: 28.5, range 0–266). All subjects also remained colonized by uropathogens. Five subjects suffered invasive UTI, 3 febrile UTI and 2 urosepsis/bacteremia, all associated with overgrowth of a urinary pathogen. Colonization with E. coli HU2117 did not impact bacterial bladder diversity, but subjects who developed infections had less diverse bladder microbiota. Conclusions Colonization with E. coli HU2117 did not prevent bladder colonization or subsequent invasive disease by uropathogens. Microbial diversity may play a protective role against invasive infection of the catheterized bladder. Trial Registration: ClinicalTrials.gov, NCT00554996 http://clinicaltrials.gov/ct2/show/NCT00554996.

Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae are the common pathogens that colonize in the nasopharynx of children. Polymicrobial interactions are thought to play an important role in different sites throughout the human body. However, there are currently very few studies that investigate the interactions between S. aureus, S. pneumoniae, and H. influenzae in the nasopharynx. We retrospectively analyzed the adenoid tissue culture from 269 children who received adenoidectomy. S. aureus, S. pneumoniae, and H. influenzae constituted the major microorganisms which were cultured from these adenoidectomies, at 23.4%, 21.6%, and 18.2%, respectively. S. pneumoniae and H. influenzae were the most prevalent in the preschool-aged children (3 < age ≤ 6), whereas S. aureus was more prevalent in infants and toddlers (age ≤ 3) and school-aged children (age > 6). Bacterial interference was found between S. aureus and S. pneumoniae and between S. aureus and H. influenzae, whereas there was an association found between S. pneumoniae and H. influenzae. The synergism and antagonism among these three species are investigated in the following paper, with the possible mechanisms involved in these interactions also discussed.

This chapter reviews aspects of interaction among the members of the respiratory microflora by considering relevant laboratory models and examples of both cooperation and competition. In general, the author focuses on the anatomic area between the nasal mucosa and the epiglottis, where several bacterial species coexist and may cocolonize for extended periods. The lower airway, below the epiglottis, is a sterile environment under normal conditions. In contrast, another neighbor of the nasopharynx, the oral cavity, is home to literally hundreds of distinct species of bacteria. Specific data regarding the anatomic localization of colonizing bacteria in the nasopharynx and the relative burdens of each species are limited; however, evolving concepts of interaction among the members of the commensal flora are furthering one's understanding of carriage. Evidence from colonization rates of children transferred from other nurseries suggested that the latter was the more likely possibility, so the investigators took the striking approach of directly testing the phenomenon of bacterial interference. In addition, many of the members of the upper respiratory flora are auxotrophs. Competition for nutrients among members of mixed bacterial populations has been proposed. Artificial alteration of colonization through vaccination or antibiotic therapy may disrupt the ecological balance in this microenvironment and have unintended consequences. Further research in this area, especially if relevant in vivo models are employed, will contribute to one's evolving understanding of the ecology of the upper respiratory tract.

Staphylococcus aureus 502A was a strain used in bacterial interference programs during the 1960s and early 1970s. Infants were deliberately colonized with 502A with the goal of preventing colonization with more invasive strains. We present the completed genome sequence of this organism.

Objectives. To examine the safety and efficacy of bacterial interference in preventing symptomatic urinary tract infection (UTI). Methods. A prospective, nonrandomized, pilot clinical trial was conducted in patients with spinal cord injury who had neurogenic bladder and had frequent episodes of symptomatic UTI. The bladder of patients was inoculated with a nonpathogenic prototype of Escherichia coli 83972. The rate of symptomatic UTI in successfully colonized patients while colonized with E. coli 83972 was compared with (a) their own baseline prestudy rate and (b) the rate of symptomatic UTI in patients who were not successfully colonized. Results. Of 44 inoculated patients, 30 (68%) became colonized with E. coli 83972 for 1 month or longer. Only two episodes of symptomatic UTI occurred in the group of 30 patients while colonized with E. coli 83972 (a total of 34 patient-years), and none was attributed to E. coli 83972. The group of 30 patients experienced a 63-fold reduction in the rate of symptomatic UTI while colonized with E. coli 83972 versus their baseline prestudy period (mean 0.06 versus 3.77 episodes of symptomatic UTI/patient-year, P

The present study was undertaken to elucidate the inhibitory activity of the normal nasopharyngeal flora against the three most common otitis media (OM) pathogens in healthy children, children with secretory otitis media (SOM) and children with recurrent otitis media (rAOM). Isolates of alpha-hemolytic streptococci (AHS) and OM pathogens were recovered from the tubal orifice in each child. The samples were taken from 20 healthy children under general anesthesia, from 19 children with SOM and 20 children with rAOM. The method used to test the bacterial interference in vitro was a modified agar overlay method. The AHS sampled from the tubal orifice of the healthy children were able to inhibit 92% of the S. peumoniae isolates, 74% of the non-typable H. influenzae isolates and 89% of the M. catarrhalis isolates. The corresponding figures for children with SOM and children with rAOM were: 73% of the S. pneumoniae isolates, 58 and 54% of the non-typable H. influenzae isolates and 86 and 89% of the M. catarrhalis isolates. The AHS from children with SOM and children with rAOM were significantly less capable of inhibiting the S. peumoniae and the H. influenzae isolates (P

Urinary tract infection (UTI) is the most common infection in patients with spinal cord injury (SCI) and is a major cause of morbidity and mortality in this population. The bladders of patients with SCI, particularly those with indwelling bladder catheters, can become colonized by a variety of organisms, including those that may, and others that may not, cause symptoms of infection. The latter group of bacteria, so-called benign colonizers, are often left untreated because they may provide some protection against symptomatic infection with more pathogenic bacteria. In recent years, deliberate urogenital tract colonization with benign bacterial strains was studied with the objective of offering some protection against invasion by uropathogenic strains. When well-characterized strains of Lactobacillus sp. were used to colonize the vagina of women prone to frequent UTI, a moderate reduction in the rate of recurrent UTI was observed. In other studies, a non-pathogenic prototype of Escherichia coli (strain 83,972) causing asymptomatic bacteriuria was used for deliberate bladder colonization. These preliminary observations encourage the examination of the safety and preventive efficacy of this approach in human subjects.

The purpose of this review is to discuss the relatively recent revival of interest in bacterial interference, particularly the use of Bifidobucferium spp. in nutrition, for treatment and prevention of disease in medicine and commercial food products by using recently developed technology. In 1910, Metchnikoff (1) first put forward the idea that the regular consumption of fermented milks might offer health benefits, the possible prophylactic and/or therapeutic properties of yogurt and related products have been the subject of much speculation. New fermented dairy products containing Lactobacillus species and Bifidobacten’um spp. have been developed and marketed in Europe, North America and the Far East. The potential “health-promoting” properties of Lactobacillus acidophilus is well documented, but possible roles of ingested bifidobacteria have not been reviewed much. Bijidobucteria are normal inhabitants of the human and animal gut, and newborns are colonized within days after birth. The population seems to be relatively stable until advanced age when it has been reported to decline. Although the population of bifidobacteria in the intestine is stable, it is influenced by diet, antibiotics, stress etc. Bifidobacteria were first described by Tissier in 1899 (2) as predominant flora in breast-fed infants. This review will consider the characteristics, ecology and role in human systems, the therapeutic and prophylactic activities of BQidobacteria, and the potential pharmaceutical and fermented products manufactured using bifidobacteria and advanced technology. The facts and the results of the some of the experiments done by different authors and the current areas of research interest and future development have also been reviewed. 0 1999 Elscvla Science Inc.

Aspects of colonization of the canine skin with bacteria are reviewed. Owing to variability in sampling techniques, anatomical sites involved and lack of temporal studies, there is still controversy as to which bacteria are residents or transients on the canine skin. The establishment of the cutaneous flora is determined by the ability of bacteria to adhere to canine corneocytes, to use available nutrients from skin secretions and to resist challenge from competing bacteria. Variations in humidity and temperature due to environment, skin folds or differences in the haircoat are also likely to have an effect. Much research has focused around Staphylococcus intermedius, the main pathogen of the canine skin but its cutaneous residency status remains questionable. Pathological conditions such as atopy and seborrhoea favour the colonization of S. intermedius and predispose to infection. Recent studies indicate that bacterial interference as a method of preventing colonization of pathogenic staphylococci may be feasible. Resume— Les aspects de la colonisation de la peau canine par des bacteries sont etudiees. A cause de la variabilite des techniques de prelevements, des sites anatomiques, et du caratere ponctuel des etudes, le doute subsiste toujours quant a savoir quelle sont les bacteries residentes ou transitoires sur la peau de chien. L'etablissement d'une flore cutanee est determinee par la capacite de la bacterie a adherer aux corneocytes canines, a utiliser les nutriments disponibles a partir des secretions cutanees et a resister aux autres bacteries qui concourent a l'occupation des memes sites. Les variations d'humidite et de temperature, dues a l'environnement, aux plis de peau et aux differences de pelage jouent probablement un role. La plupart des etudes concernent Staphylococcus intermedius, l'agent pathogene principal de la peau du chien, mais son statut de resident cutane est toujours debattu. Des conditions pathologiques telles que l'atopie et la seborrhee favorisent la colonisation par S. intermedius et predisposent a l'infection. Des etudes recentes indiquent que l'interference bacterienne peut etre envisagee comme une methode de prevention de la colonisation cutanee par un staphylocoque pathogene. [Saijonmaa-Koulumies, L. & Lloyd, D. H. Colonization of the canine skin with bacteria (Colonisation de la peau canine par des bacteries). Veterinary Dermatology 1996; 7: 153–162.] Resumen Se revisan algunos aspectos de la colonizacion bacteriana en la piel canina. Existe aun controversia sobre que bacterias son residentes o transitorias en la piel del perro, debido a la variabilidad en las tecnicas de recoleccion, localizacion y falta de estudios temporales. El establecimiento de la flora cutanea depende de su capacidad de adhesion a los corneocitos, de utilizar los nutrientes de las secreciones cutaneas y de resistir la competencia de otras bacterias. Tambien es probable que tengan un papel los cambios de humedad y temperatura por los pliegues cutaneos o las diferencias en el pelaje. Se ha centrado mucha investigacion en Staphylococcus intermedius, el principal patogeno de la piel canina, aunque se sigue cuestionando su existencia como residente cutaneo. Situaciones patologicas como la atopia o la seborrea favorecen la colonizacion por S. intermedius y predisponen a infeccion. Algunos estudios recientes indican que es factible la interferencia bacteriana como metodo de prevenir la colonizacion por estafilococos patogenos. [Saijonmaa-Koulumies, L. & Lloyd, D. H. Colonization of the canine skin with bacteria (Colonizacion de la piel cannina con bacterias). Veterinary Dermatology 1996; 7: 153–162.] Zusammenfassung— Es werden Aspekte der Besiedelung der Hundehaut mit Bakterien dargestellt. Entsprechend der Variabilitat in der Probenentnahme, verwendeten anatomischen Regionen und dem Mangel an temporaren Studien exisitieren immer noch unterschiedliche Ansichten, ob Bakterien auf der Haut des Hundes als resident oder transient gelten. Die Aufstellung der kutanen Flora wird durch die Fahigkeit der Bakterien bestimmt, sich an die kaninen Korneozyten anzuheften, verfugbare Nahrstoffe aus den Hautsekretionen zu verwenden und sich gegenuber konkurrierenden Keimen zu behaupten. Veranderungen in Feuchtigkeit und Temperatur in Abhangigkeit von Umgebung, Hautfalten oder Unterschieden im Haarkleid scheinen ebenfalls einen Effekt zu besitzen. Viele Untersuchungen konzentrierten sich auf Staphylococcus aureus, der hauptpathogene Keim auf der Hundehaut, aber sein Status als residenter Keim bleibt fraglich. Pathologische Zustande wie Atopie und Seborrhoe begunstigen die Besiedelung mit S. intermedius und pradisponieren fur eine Infektion. Kurzliche Studien zeigen, das bakterielle Interferenzen als Methode zur Verhinderung der Ansiedlung von pathogenen Staphylokokken moglich sein konnten. [Saijonmaa-Koulumies, L., Lloyd, D.H. Colonization of the canine skin with bacteria (Besiedelung der Haut des Hundes mit Bakterien). Veterinary Dermatology 1996; 7: 153–162.]

Antagonism against Staphylococcus intermedius was investigated amongst bacteria isolated from skin and mucosae of (1) 15 dogs with pyoderma and (2) 42 healthy dogs, including household pets, laboratory beagles and guide dogs. Fifteen isolates of S. intermedius, four coagulase-negative staphylococci and a Micrococcus were inhibitory in vitro against at least one of the three indicator strains using direct and deferred inhibition tests. More dogs with antagonists were found in the pyoderma group and amongst laboratory beagles (p < 0.05) compared to healthy household pets. The frequency of all antagonists and of antagonistic S. intermedius from mucosae was higher in the pyoderma group compared to healthy household pets (p < 0.01 for both) and all healthy animals (p < 0.05 and p < 0.01, respectively). Increased competition at mucosae of infected dogs caused by higher populations of bacteria may have favoured the selection of antagonistic strains. Further studies, including tests for adherence and virulence are required to determine whether these isolates could be used as interfering strains against canine pyoderma. Resume- L'antagonisme contre Staphylococcus intermedius a eteetudie parmi des bacteries isolees a partir de la peau et des muqueuses de 15 chiens presentant des pyodermites et de 42 chiens sains, effectif comprenant des chiens de particuliers, des beagles de laboratoire et des chiens guides. Parmi les souches isolees, 15 S. intermedius, 4 staphylocoques coagulase negatifs et un micrococcus se sont reveles inhibiteurs in vitro vis a vis d'au moins une des 3 souches indicatrices, a la fois dans des test d'inhibition directs et indirects. La plupart des chiens portcurs d'antagonistes appartenait au groupe pyodermite et au groupe beagles de laboratoire (p < 0,05) plutot qu'au groupe chiens de particuliers sains. La frequence de tous les antagonistes et du S. intermedius antagoniste isoles a partir des muqueuses etait superieure dans le groupe pyodermite par rapport au groupe chiens de particuliers sains (p < 0,01) pour les 2) et au groupe incluant la totalite des animaux sains (p

We hypothesized that pretreating urinary catheters with benign Escherichia coli HU2117 plus an antipseudomonal bacteriophage (ΦE2005-A) would prevent Pseudomonas aeruginosa biofilm formation on catheters--a pivotal event in the pathogenesis of catheter-associated urinary tract infection (CAUTI).Silicone catheter segments were exposed to one of four pretreatments (sterile media; E. coli alone; phage alone; E. coli plus phage), inoculated with P. aeruginosa and then incubated up to 72 h in human urine before rinsing and sonicating to recover adherent bacteria. Pseudomonas aeruginosa adherence to catheters was almost 4 log(10) units lower when pretreated with E. coli plus phage compared to no pretreatment (P0.001) in 24-h experiments and more than 3 log(10) units lower in 72-h experiments (P0.05). Neither E. coli nor phage alone generated significant decreases.The combination of phages with a pre-established biofilm of E. coli HU2117 was synergistic in preventing catheter colonization by P. aeruginosa.We describe a synergistic protection against colonization of urinary catheters by a common uropathogen. Escherichia coli-coated catheters are in clinical trials; adding phage may offer additional benefit.

Aims Meticillin-resistant Staphylococcus aureus (MRSA) ST398 continues to spread amongst pigs and other domestic animals and man. This highlights the need for models to examine MRSA colonization and investigate control strategies. This study aimed to develop a gnotobiotic pig model and assess the potential of bacterial interference from selected coagulase-negative staphylococci (CNS) against MRSA ST398. Methods and Results Groups of 2-week-old piglets were atraumatically inoculated either with MRSA and/or CNS. Skin and mucosae were swabbed, and bacterial counts compared over a period of 21 days. Piglets developed healthily, and bacterial populations increased similarly for both MRSA and CNS until day 32. On day 37, MRSA counts in groups with CNS reduced significantly compared with MRSA alone (P = 0·03). Conclusions The results showed that inoculation of piglet skin with MRSA resulted in spontaneous colonization and that MRSA ST398 has a low pathogenic potential in gnotobiotic piglets. Quantitative bacteriology indicated that initial MRSA colonization was unaffected by concurrent CNS colonization but that interference may occur over a longer period. Significance and Impact of the Study Gnotobiotic piglets provide a reproducible model suitable for bacterial interference studies, which should be further explored as an alternative to antimicrobials in the control of MRSA.

Staphylococcus aureus nasal carriage is a risk factor for infection in humans, particularly in the hospital setting. Bacterial interference was used as an alternative strategy for the prevention of upper respiratory, urogenital and gastrointestinal tract infections. This study was designed to assess if the administration of a live-attenuated aroA mutant of S. aureus is useful as a potential approach to prevent transient staphylococcal nasal carriage by virulent strains. We constructed an aroA mutant of S. aureus Newman strain by homologous recombination. The auxotrophic NK41 mutant was attenuated as determined by the increase of the LD50 after intraperitoneal challenge. In mice, previous nasal colonization with the NK41 mutant significantly reduced the number of CFU of S. aureus (HU-71 and Hde288) clinical isolates and the parental Newman strain. The NK41 mutant was unable to induce a pro-inflammatory response and to damage the invaded human respiratory epithelial cells. Moreover, the cells previously or simultaneously infected with the NK41 mutant were invaded by virulent strains in a significantly lower degree than those of the control group. In conclusion, the attenuated NK41 mutant interfered with the colonization and establishment of pathogenic strains of S. aureus, which produce severe infections. © 2011 Institut Pasteur. Fil: Barbagelata, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina Fil: Álvarez, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina Fil: Gordiola, Mariana Laura. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina Fil: Tuchscherr, Lorena Paola Nelly. Münster Universitätsklinikum Münster; Alemania Fil: von Eiff, Cristoff. Münster Universitätsklinikum Münster; Alemania Fil: Becker, Karsten. Münster Universitätsklinikum Münster; Alemania Fil: Sordelli, Daniel Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina Fil: Buzzola, Fernanda Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina

The palatine tonsils and nasopharyngeal adenoids represent the predominant immunocompetent tissue of the upper respiratory tract. Its major function is as a first line of defense against viral, bacterial, and food antigens that enter the upper aerodigestive system. Another major function of the tonsils and adenoids is to supply the local mucosal immune system of the upper respiratory tract with dimeric IgA-producing B cells. Secretory IgA has particular hydrophilic properties and is capable of preventing adsorption and penetration of bacteria and/or viruses into the upper respiratory tract mucosa. In addition, the role of the indigenous flora of the upper respiratory tract, particularly the viridans streptococci has been emphasized as providing a valuable source of bacterial interference to the colonization of potential pathogens.

MICROBIOLOGYWork presented last week at the annual meeting of the American Society for Cell Biology in San Francisco suggests that applying a harmless bacterium or its products to surgical wounds may thwart infections by the dangerous pathogen Staphylococcus aureus , a major cause of hospital-acquired infections. Although physicians have previously pitted one bacterium against another to prevent infections of the intestinal and genitourinary tracts, this is the first attempt to use a friendly microbe to prevent infection of surgical wounds, say experts. The findings also point to a possible mechanism for this "bacterial interference." They suggest that a protein secreted by the harmless bacterium prevents the pathogen from getting a foothold in injured tissue.

Biofilms are structured communities characterized by distinctive gene expression patterns and profound physiological changes compared to those of planktonic cultures. Here, we show that many gram-negative bacterial biofilms secrete high levels of a small-molecular-weight compound, which inhibits the growth of only Escherichia coli K-12 and a rare few other natural isolates. We demonstrate both genetically and biochemically that this molecule is the amino acid valine, and we provide evidence that valine production within biofilms results from metabolic changes occurring within high-density biofilm communities when carbon sources are not limiting. This finding identifies a natural environment in which bacteria can encounter high amounts of valine, and we propose that in-biofilm valine secretion may be the long-sought reason for widespread but unexplained valine resistance found in most enterobacteria. Our results experimentally validate the postulated production of metabolites that is characteristic of the conditions associated with some biofilm environments. The identification of such molecules may lead to new approaches for biofilm monitoring and control.

Biofilm/bioslime is a complex, dynamically interactive multicellular community protected within a heterogeneous exopolysaccharide matrix. Its formation results in the genesis or perpetuation of infection, enhancement of inflammation, and tissue damage or death. Industrial financial losses result from biofilm/bioslime formation; however, the consequences in the medical realm are equally devastating. The relation of biofilm to patients with chronic kidney disease is often covert and extends beyond the colonization of hemodialysis circuits and vascular accesses. Urinary tract device– and vascular access–related biofilms may also increase the burden of cardiovascular risk borne by chronic kidney disease patients, synergizing with the chronic inflammatory state already incurred by these individuals. Current anti-infective strategies are aimed at rapidly killing planktonic forms of microorganisms without specifically targeting the sessile forms that perpetuate their planktonic brethren. Future treatments of infections must ultimately target these reservoirs of infection aiming for their complete eradication. Presently, included among these novel weapons of microdestruction are molecular blockading techniques, electrical enhancement of anti-infectives, and bacterial interference. Nonetheless, the best approach against biofilm formation remains the prevention of microbial colonization, which can be largely by sterile handling of patient-related devices, the most well-established biofilm reservoirs.

Device-related bacterial colonization of the urinary tract and, occasionally, invasive infection are among the most common management problems encountered by infectious diseases consultants. Our usual response is to urge limits on catheter use, avoid treating asymptomatic infection, and anticipate occasional, sometimes life-threatening invasive infections. This advice is generally viewed as being not very helpful. During the 1960s, progress was made with the introduction of closed urinary drainage systems for patients requiring short-term catheterization and intermittent catheter use for patients with neurologically impaired bladders. Otherwise, little has changed in the past quartercentury. We have learned that pyuria accompanying bacteriuria has no particular significance, that even though we may only identify 1 pathogen in a urine culture, multiple organisms are frequently resident in the urinary tract-which is overgrown by the most rapidly grown organism-and that impregnation of catheters with antimicrobial substances has limited (if any) value in the prevention of bacteriuria.

This prospective, randomized, placebo-controlled, double-blind pilot trial examined the efficacy of bacterial interference in preventing urinary tract infection (UTI) in 27 patients with spinal cord injury. Patients whose bladders became colonized with Escherichia coli 83972 were half as likely (P=.01) than noncolonized patients to develop UTI during the subsequent year.

In vitro and in vivo studies have shown that various strains of ''viridans streptococci'' (nongroupable alpha-hemolytic streptococci) inhabiting the oropharynx suppress the growth of gram-positive and gram-negative microorganisms. We conducted an inventory of the oropharyngeal flora from ambulatory asthma and chronic obstructive pulmonary disease (COPD) patients and a control group to examine the interaction between viridans streptococci and potential pathogens in vivo. In addition, the difference in colonization patterns of these bacteria was studied. Oral washings from 195 patients, 48 asthma (24.6%), 147 COPD (75.4%), and 157 control subjects were examined microbiologically on two occasions with a 2-wk interval, resulting in a total of 384 and 295 oral washings, respectively. All patients were ina stable phase of disease throughout the study. The distribution of low (less than or equal to 10(4)/ml) or high (greater than or equal to 10(5)/ml) concentrations of viridans streptococci did not differ substantially between asthma or COPD patients and control subjects. Potentially pathogenic microorganisms found in a low (less than or equal to 10(4)/ml) or high (greater than or equal to 10(5)/ml) concentration were equally distributed between the two groups. Staphylococcus aureus and beta-hemolytic streptococci were found significantly less often in the asthma and COPD group (p

The aim of the investigation was to study the influence of various penicillin levels on the interference between alfa- and beta-streptococci based on antibiotic levels registered after oral intake of penicillin tablets. It was found that penicillin was released from ordinary sugar coated tablets already in the mouth resulting in concentrations in saliva above the MIC of most penicillin sensitive microorganisms during the first 2 min. This was followed by a decrease of the alfa-streptococcal flora. It was also shown that penicillin levels above the MIC of alfa-streptococci resulted in prolonged survival of beta-streptococci as compared to that noted at penicillin levels above the MIC of beta-streptococci but below that of the alfa-strains. At this latter level a synergistic effect between penicillin and interfering alfa-streptococcal strains could be demonstrated.

Interaction between Escherichia coli and Pseudomonas aeruginosa was studied in chronic bladder infection made in male Wistar rats by implanting a knotted silk thread holding organisms into the bladder. Strains isolated from patients were used. The number of organisms in bladder urine was measured 1 week after the inoculation. When E. coli and P. aeruginosa were inoculated simultaneously, P. aeruginosa grew less well than when inoculated alone. When P. aeruginosa was inoculated into the bladder colonized with E. coli, P. aeruginosa was almost always unable to grow in the bladder, while E. coli inoculated into the bladder colonized with P. aeruginosa was able to grow there in many animals. Bacteriocin activity had nothing to do with the results. These results indicate that E. coli interferes with the growth of P. aeruginosa in mixed infection in the bladder.