Specific Bacterial Infections Research Articles

Backbone 1H, 15N, and 13C resonance assignments of the Tom1 VHS domain.

Efficient trafficking of ubiquitinated receptors (cargo) to endosomes requires the recruitment of adaptor proteins that exhibit ubiquitin-binding domains for recognition and transport. Tom1 is an adaptor protein that not only associates with ubiquitinated cargo but also represents a phosphoinositide effector during specific bacterial infections. This phosphoinositide-binding property is associated with its N-terminal Vps27, Hrs, STAM (VHS) domain. Despite its biological relevance, there are no resonance assignments of Tom1 VHS available that can fully characterize its molecular interactions. Here, we report the nearly complete 1H, 15N, and 13C backbone resonance assignments of the VHS domain of human Tom1.

Mixed Infections of the Paronychium with Prevotella bivia

We encountered and treated two cases of Prevotella bivia in mixed aerobic/anaerobic paronychia within a period of 1 year. Upon reviewing the literature, we found a dearth of both experimental and anecdotal evidence of this specific bacterial infection, with only one case of P. bivia in the hand having been reported [1]. The most prevalent pathogen in acute paronychia is Staphylococcus aureus, which is the causative bacterium in 50 to 80% of cases [2–4]. However, anaerobic infections, especially mixed aerobic/anaerobic infections, are becoming increasingly common [1, 5–7]. Mixed infections, not uncommon in paronychia, provide a fertile environment for the exchange of genetic material, thus increasing both the severity of infection and the chance of developing bacterial resistance [8–10]. Gram-negative anaerobes, which have been proven to induce a pro-inflammatory response, are normally the anaerobes involved in these mixed infections [2, 5, 7, 10, 11]. P. bivia is an anaerobic, non-pigmented, Gram-negative bacillus species which naturally thrives in the human female vaginal tract and occasionally is found in the oral flora [1, 5, 12, 13]. Due to its ability to grow abundantly in the presence of estrogen, P. bivia is traditionally implicated in vaginal tract infections such as endometritis and pelvic inflammatory disease [5, 13]. However, P. bivia has also been found in rare locations such as the nail bed, chest wall, intervertebral discs, and even the hip and knee joints [5, 10, 14–16]. If left untreated, it may lead to more serious conditions, including necrotizing fasciitis, osteomyelitis, or septic arthritis [12, 17–20]. In recent reports, the general consensus for treating paronychial infections has been broad spectrum antibiotics such as oral amoxicillin/clavulanate or oral clindamycin [2, 11, 21]. These choices are intended to provide broad coverage of both aerobic and anaerobic species, regardless of susceptibility testing. The challenging aspect of mixed infections is that susceptibility testing for anaerobes is not well standardized [22]. Also, some P. bivia strains have actually shown resistance to broad spectrum antibiotics such as clindamycin [9]. Thus, confusion still exists over how to treat these infections. The following cases shed some light on how the aerobic pathogen may be a new target for treating these mixed infections.

Variation in 60-day Readmission for Surgical-site Infections (SSIs) and Reoperation Following Spinal Fusion Operations for Neuromuscular Scoliosis.

Readmission for surgical-site infection (SSIs) following spinal fusion for NMS impacts costs, patient risk, and family burden; however, it may be preventable. The purpose of this study was to examine variation in hospital performance based on risk-standardized 60-day readmission rates for SSI and reoperation across 39 US Children's Hospitals. Retrospective cohort study using the Pediatric Health Information Systems (PHIS) database involving children aged 10 to 18 years with ICD9 codes indicating spinal fusion, scoliosis, and neuromuscular disease discharged from 39 US children's hospitals between January 1, 2007 and September 1, 2012. Readmissions within 60 days for SSI were identified based on the presence of ICD9 codes for (1) infectious complication of device or procedure, or (2) sepsis or specific bacterial infection with an accompanying reoperation. Logistic regression models accounting for patient-level risk factors for SSI were used to estimate expected (patient-level risk across all hospitals) and predicted (weighted average of hospital-specific and all-hospital estimates) outcomes. Relative performance was determined using the hospital-specific predicted versus expected (pe) ratios. Average volume across hospitals ranged from 2 to 23 fusions/quarter and was not associated with readmissions. Of the 7560 children in the cohort, 534 (7%) were readmitted for reoperation and 451 (6%) were readmitted for SSI within 60 days of discharge. Reoperations were associated with an SSI in 70% of cases. Across hospitals, SSI and reoperation rates ranged from 1% to 11% and 1% to 12%, respectively. After adjusting for age, sex, insurance, presence of a gastric tube, ventriculoperitoneal shunt, tracheostomy, prior admissions, number of chronic conditions, procedure type (anterior/posterior), and level (>9 or <9 vertebrae), pe ratios indicating hospital performance varied by 2-fold for each outcome. After standardizing outcomes using patient-level factors and relative case mix, several hospitals in this cohort were more successful at preventing readmissions for SSIs and reoperations. Closer examination of the organization and implementation of strategies for SSI prevention at high-performing centers may offer valuable clues for improving care at lower performing institutions. Level III.

Inflammasome Involvement in Alzheimer's Disease.

Inflammasomes are responsible for the maturation of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-18, and IL-33 and activation of inflammatory cell death, pyroptosis. They assemble in response to cellular infection and stress or to tissue damage, promote inflammatory reactions, and are important in regulating innate immunity particularly by acting as platforms for activation of caspase proteases. They appear to be involved in several pathological processes activated by microbes including Alzheimer's disease (AD). Best characterized in microbial pathogenesis is the nucleotide-binding domain and leucine-rich repeat (NLR)-protein 3 (NLRP3) inflammasome. AD is a neurodegenerative condition in which the neuropathological hallmarks are the deposition of amyloid-β (Aβ) and hyperphosphorylated tau protein coated neurofibrillary tangles. For decades, the role of the innate immune system in the etiology of AD was considered less important, but the recently discovered inflammatory genes by genome-wide association studies driving inflammation in this disease has changed this view. Innate immune inflammatory activity in the AD brain can result from the pathological hallmark protein Aβ as well as from specific bacterial infections that tend to possess weak immunostimulatory responses for peripheral blood myeloid cell recruitment to the brain. The weak immunostimulatory activity is a consequence of their immune evasion strategies and survival. In this review we discuss the possibility that inflammasomes, particularly via the NLR family of proteins NLRP3 are involved in the pathogenesis of AD. In addition, we discuss the plausible contribution of specific bacteria playing a role in influencing the activity of the NLRP3 inflammasome to AD progression.

Prevalence and antibiotic resistance of bacterial pathogens isolated from childhood diarrhea in Beijing, China (2010-2014).

BackgroundDiarrhea is one of the main causes of morbidity and mortality among children less than 5 years of age worldwide, and its causes vary by region. This study aimed to determine the etiologic spectrum, prevalent characteristics and antimicrobial resistance patterns of common enteropathogenic bacteria from diarrheagenic children in Beijing, the capital of China.MethodsStool samples were collected from 2524 outpatients who were aged 0–5 years in Beijing, China during 2010–2014. Microbiological methods, real-time PCR and antimicrobial susceptibility test were used to identify the bacterial causes and antimicrobial resistance patterns in the isolates.ResultsOf the 2524 patients screened, we identified the causes of 269 cases (10.7 %) as follows: diarrheagenic Escherichia coli (4.6 %), Salmonella (4.3 %), Shigella (1.4 %) and Vibrio parahaemolyticus (0.4 %). Atypical EPEC, Salmonella enteritidis, Shigella sonnei and serotype O3:K6 were the most common serogroups or serotypes of the four etiological bacteria. The prevalence of pathogens was correlated with age, season and clinical symptoms. The highest proportion of all causative bacteria was found in children aged 3–5 years and in summer. The clinical symptoms associated with specific bacterial infection, such as fever; abdominal pain; vomiting; and watery, mucus, and bloody stool, were observed frequently in diarrheal patients. Salmonella showed moderate rates of resistance (40–60 %) to ampicillin, nalidixic acid, streptomycin and sulfisoxazole. Resistance to at least three antimicrobials was found in 50 % of isolates. Of the top three serotypes in Salmonella, high-level antimicrobial resistance to single and multiple antibiotics was more common among Salmonella typhimurium and Salmonella 1, 4, [5], 12:i:- than among S. enteritidis. More than 90 % of Shigella isolates showed more alarming resistance to most antibiotics, with a widened spectrum compared to Salmonella.ConclusionConstant antibiotic surveillance is warranted because the bacteria were highly resistant to various antimicrobials. Our study contributes to the strengthening of the existing surveillance system and provides aid for effective prevention and control strategies for childhood diarrhea.Electronic supplementary materialThe online version of this article (doi:10.1186/s13099-016-0116-2) contains supplementary material, which is available to authorized users.

Etiologic Framework for the Study of Neurodegenerative Disorders as Well as Vascular and Metabolic Comorbidities on the Grounds of Shared Epidemiologic and Biologic Features.

Background: During the last two decades, protein aggregation at all organismal levels, from viruses to humans, has emerged from a neglected area of protein science to become a central issue in biology and biomedicine. This article constitutes a risk-based review aimed at supporting an etiologic scenario of selected, sporadic, protein-associated, i.e., conformational, neurodegenerative disorders (NDDs), and their vascular- and metabolic-associated ailments.Methods: A rationale is adopted, to incorporate selected clinical data and results from animal-model research, complementing epidemiologic evidences reported in two prior articles.Findings: Theory is formulated assuming an underlying conformational transmission mechanism, mediated either by horizontal transfer of mammalian genes coding for specific aggregation-prone proteins, or by xeno-templating between bacterial and host proteins. We build a few population-based and experimentally-testable hypotheses focusing on: (1) non-disposable surgical instruments for sporadic Creutzfeldt-Jakob disease (sCJD) and other rapid progressive neurodegenerative dementia (sRPNDd), multiple system atrophy (MSA), and motor neuron disease (MND); and (2) specific bacterial infections such as B. pertussis and E. coli for all forms, but particularly for late-life sporadic conformational, NDDs, type 2 diabetes mellitus (T2DM), and atherosclerosis where natural protein fibrils present in such organisms as a result of adaptation to the human host induce prion-like mechanisms.Conclusion: Implications for cohort alignment and experimental animal research are discussed and research lines proposed.

The Roles of Type I Interferon in Bacterial Infection.

Type I interferons (IFNs) are pleiotropic cytokines well recognized for their role in the induction of a potent antiviral gene program essential for host defense against viruses. They also modulate innate and adaptive immune responses. However, the role of type I IFNs in host defense against bacterial infections is enigmatic. Depending on the bacterium, they exert seemingly opposite and capricious functions. In this review, we summarize the effect of type I IFNs on specific bacterial infections and highlight the effector mechanisms regulated by type I IFNs in an attempt to elucidate new avenues to understanding their role.

Presence of Porphyromonas gingivalis in esophagus and its association with the clinicopathological characteristics and survival in patients with esophageal cancer.

BackgroundMounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. However, the possible role of the keystone periodontal pathogen, Porphyromonas gingivalis, in esophageal squamous cell carcinoma (ESCC) remains unknown. Therefore, we examined the presence of P. gingivalis in esophageal mucosa, and the relationship between P. gingivalis infection and the diagnosis and prognosis of ESCC.MethodsThe presence of P. gingivalis in the esophageal tissues from ESCC patients and normal controls was examined by immunohistochemistry using antibodies targeting whole bacteria and its unique secreted protease, the gingipain Kgp. qRT-PCR was used as a confirmatory approach to detect P. gingivalis 16S rDNA. Clinicopathologic characteristics were collected to analyze the relationship between P. gingivalis infection and development of ESCC.ResultsP. gingivalis was detected immunohistochemically in 61 % of cancerous tissues, 12 % of adjacent tissues and was undetected in normal esophageal mucosa. A similar distribution of lysine-specific gingipain, a catalytic endoprotease uniquely secreted by P. gingivalis, and P. gingivalis 16S rDNA was also observed. Moreover, statistic correlations showed P. gingivalis infection was positively associated with multiple clinicopathologic characteristics, including differentiation status, metastasis, and overall survival rate.ConclusionThese findings demonstrate for the first time that P. gingivalis infects the epithelium of the esophagus of ESCC patients, establish an association between infection with P. gingivalis and the progression of ESCC, and suggest P. gingivalis infection could be a biomarker for this disease. More importantly, these data, if confirmed, indicate that eradication of a common oral pathogen could potentially contribute to a reduction in the overall ESCC burden.Electronic supplementary materialThe online version of this article (doi:10.1186/s13027-016-0049-x) contains supplementary material, which is available to authorized users.

Infection and preterm birth

Preterm birth (PTB) remains a primary cause of neonatal morbidity and mortality. The purpose of this article is to outline the association between infection and PTB. We performed a search of the PubMed database for relevant scientific work published in English from 1995 to July 2015. Whereas there is substantial evidence regarding infection as a strong risk factor for preterm birth, the role of specific bacterial and viral infections is not totally conclusive. Newer high-dimensional biological technologies such as microbiomics and metabolomics offer hope to identify the causative pathogens. In addition, strategies have been developed to reduce PTB.

Obesity as an infectious disease– review of the literature

Obesity, which is a pathological and excessive accumulation of body fat (WHO; World Health Organization), is the problem undertaken in the world literature for several decades. Significant mortality due to the obesity comorbidities is the basis to undertake an intensive work on the new preventive and therapeutic strategies worldwide. Nevertheless, due to the multifactorial origin of obesity and the growing number of obese subjects, the effectiveness of these strategies appears to be highly limited. Besides to the traditionally recognized etiological factors of obesity, many reports showing an association of infectious agents and uncontrolled weight gain have been published recently. In this paper we present an overview of reports confirming the association between infections and obesity. Data showed that a specific viral and bacterial infections as well as infections with protozoa and prions are associated with the increased intracellular accumulation of lipids, hypertrophy and hyperplasia of adipose tissue, body weight gain, increase of BMI and changes in lipid metabolism. These infections can serve as direct causal agents, but they can also interact with other environmental factors, thus increasing the predisposition to the development of obesity. There are at least a few hypotheses on the pathogenesis of “infectobesity.” There are some reports describing the damage of the central nervous system and hence the endocrine glands dysfunction due to infection, increased insulin susceptibility of infected cells, reduced production and release of leptin, increased glucose and fatty acids transport into adipocytes and inflammatory basis for infectobesity. Undoubtedly, awareness of the relationship between infections and obesity brings us closer to develop the effective preventive and therapeutic strategies, but it also raises the question about other, so far underestimated, environmental factors that increase the predisposition to obesity.

Studies on Anti microbial Potential of Non-antibiotics on Resistant Bacteria – A Review

The non-chemotherapeutic compounds, synthetic compounds and naturally isolated compounds possess good antimicrobial activity against microbial infections is a well-known fact. In this state the term non-antibiotics is taken to include a variety of pharmacologically active compounds which are useful in the management of pathological conditions of anon-infectious diseases that modify cell permeability and have been shown to exhibit broad spectrum antimicrobial activity. Of the nonantibiotic medicinal compounds, neuroleptic as well as phenothiazine inhibited the extracellular and intracellular efflux pump system and particularly intracellular efflux pumps has been the main research focus in multidrug resistant gram positive and gram negative microorganisms. The increase and spread of drug resistance is exerted by unsystematic usage of antibiotics for prolonged periods and over use of antimicrobials. Antimicrobial agents are inactivated by the following resistance mechanisms. Multi drug efflux pump and alteration of membrane protein are based on the persistence of resistance genes. A review of literature on a number of research articles suggests that some of these and other membrane active compounds improve the activity of conventional antibiotics, eliminate the natural resistance to particular antibiotics, and exhibit good activity against multi drug resistant form of Mycobacterium tuberculosis and methicillin resistant staphylococcus aureus. Thus, non-antibiotics particularly anti depressants, antipsychotics, anti-hypertensive agent, anti-spasmodic drug, anti-inflammatory agent and Cardio vascular drug have a significant role in the treatment of microbial infections which had shown their synergistic effect with penicillin and some other antibiotics. These effects would help to reduce the dose of antibiotics to patients suffering from specific bacterial infections.

Studies on Estrual Cervical Mucus of Repeat Breeding Cows with Special Reference to Ovulatory Disturbances and Genital Infection

A total of 100 crossbred Jersey cows comprising of 80 repeat breeder presented for treatment and 20 clinically healthy (control group) animals presented for artificial Insemination at their first service within 60–90 days following calving were selected. Estrual cervical mucus were examined for physical properties and white side test (WST). Effects of ovulatory disturbances and non specific bacterial genital infection on physical properties of cervical mucus were also determined. The volume, colour, consistency, stringiness, fern pattern and spinnbarkeit values of cervical mucus were not affected by ovulatory disturbances, while, colour, consistency and pH showed significant (p < 0.01) changes due to non-specific bacterial genital infection. The results of WST showed significant (p < 0.01) positive correlation (0.484) with bacterial culture. It is concluded that ovulatory disturbances have no impact on altering physical characteristics of estrual cervical mucus; however, colour, consistency and pH of cervical mucus are greatly influenced by nonspecific bacterial genital infection in repeat breeding cattle.

The diagnostic value of adenosine deaminase activity in pulmonary tuberculosis: Comparison between sputum and serum

BackgroundTuberculosis is a chronic specific bacterial infection caused by bacteria of the Mycobacterium tuberculosis. It remains one of the deadliest diseases in the world. It is the second leading infectious cause of death after HIV infection. Adenosine deaminase (ADA) activity is increased in various conditions such as liver disease, tuberculosis, typhoid, infective mononucleosis and certain malignancies, especially those of haematopoietic origin. ObjectiveThe aim of the work was to assess the diagnostic value of ADA in pulmonary tuberculosis by comparing levels in sputum and serum. Subjects and methodsThe present study included 15 patients with active pulmonary tuberculosis, 15 patients with pneumonia and 15 patients diagnosed as lung cancer. All patients were subjected to: Full history taking, complete clinical examination, laboratory investigations, and plain X-ray chest. Measurement of sputum and serum level of ADA of all patients using specific immunoassay method. ResultsThere was a significant increase in sputum ADA in tuberculous group in relation to the other groups (mean sputum ADA was 159.76±16.95, 84.34±6.87 and 67.30±7.47U/L, respectively). The mean serum ADA was 31.99±8.85, 24.15±4.22and 14.84±2.43U/L in tuberculous group, pneumonia group and bronchogenic carcinoma group, respectively. There was a statistically significant increase in serum ADA in the tuberculous group in relation to the other groups (F 10.65, P 0.001∗). There was a statistically significant positive correlation between sputum and serum ADA (r=0.75, P=0.0001). ConclusionThe results support the feasibility of using sputum ADA for diagnosis of pulmonary tuberculosis.

Risk Factor for Periodontitis

Periodontal disease possesses a significant challenge to the patient and the oral health care professional equally .Risk factor that are associated with periodontal disease must be properly identified and examine by professional before the patient is treated by periodontal treatment. It is important as how we educate a patient on risk management .This article offers strategies for professional to use and helps in establishing a balance preventive oral management plan. Pathogenesis of periodontal disease is more complex than the presence of virulent microorganism. Susceptibility to periodontitis varies between individuals who carry the same pathogenic micro flora. I. Introduction- All individuals are uniformly susceptible to developing periodontal disease. Accumulation of plaque, poor oral hygiene and occlusion trauma are sufficient to initiate periodontitis however during the past four decades it is believed that periodontal disease is caused by specific bacterial infections and that individuals are uniformly susceptible neither to these infections nor to the damage caused by them. So the main concentration is to find about the developing markers that allows identification of susceptible individuals prior to developing periodontitis and identifying risk factor that can be modified in order to prevent or alter the periodontal disease. Risk factors- Risk can be identified in terms of risk factor, determinant, indicators, and predictors. A risk factor is any attribute, characteristic or exposure of individuals that increases the likelihood of developing a disease.it can be environmental, behavioural,or biologic factors. Risk determinant should be reserved for that risk factor that cannot be modified. Risk indicator have been identified in cross sectional studies but not confirmed through longitudinal studies. Risk predictors, although associated with increased risk for disease, do not cause the disease.

Hirschsprung’s Disease and the Intestinal Microbiome

Hirschsprung-associated enterocolitis (HAEC) is the most common and serious complications of Hirschsprung's disease (HD), having mortality rate of 1-10%. Despite many proposed etiologies, the pathological mechanisms underlying HAEC are still unclear. The specific bacterial or viral infections are among the key factors to consider. The study of HAEC related intestinal flora was limited by the fact that 85% of intestinal microbiota cannot be cultured. The developments of modern next generation sequencing platforms and metagenomics methodology allowed to study and characterize the intestinal microbiota in infants with Hirschsprung’s disease with a great precision. This article reviews the progress in study of Hirschsprung’s disease and intestinal microbiota in patients with and without enterocolitis.

Functional characterization of thioredoxin 3 (TRX-3), a Caenorhabditis elegans intestine-specific thioredoxin

Thioredoxins are a class of evolutionarily conserved proteins that have been demonstrated to play a key role in many cellular processes involving redox reactions. We report here the genetic and biochemical characterization of Caenorhabditis elegans TRX-3, the first metazoan thioredoxin with an intestine-specific expression pattern. By using green fluorescent protein reporters we have found that TRX-3 is expressed in both the cytoplasm and the nucleus of intestinal cells, with a prominent localization at the apical membrane. Although intestinal function, reproductive capacity, longevity, and resistance of trx-3 loss-of-function mutants to many stresses are indistinguishable from those of wild-type animals, we have observed a slight reduction in size and a minor reduction in the defecation cycle timing of trx-3 mutants. Interestingly, trx-3 is induced upon infection by Photorhabdus luminescens and Candida albicans, and TRX-3 overexpression provides a modest protection against these pathogens. Together, our data indicate that TRX-3 function in the intestine is dispensable for C. elegans development but may be important to fight specific bacterial and fungal infections.

Periodontopathogen and Epstein-Barr Virus-Associated Periapical Periodontitis May Be the Source of Retrograde Infectious Peri-Implantitis

Herpesviral-bacterial synergism may play a role in periodontitis and peri-implantitis etiopathogenesis. Periapical periodontitis (PP) lesions can predict future apical peri-implantitis complications. This pilot study aimed to substantiate herpesviral-bacterial coinfection in symptomatic (SP) and asymptomatic (AP) PP and assess associations with periodontopathogen salivary contamination in patients receiving implants. Polymerase chain reaction (PCR)-based identification was performed on PP granulation tissue (GT) from 33 SP and AP patients and compared with unstimulated whole saliva. Quantitative PCR evaluated Epstein-Barr virus (EBV) and cytomegalovirus copy counts. SP GT had higher proportions of periodontopathogens. Symptomatic patients were 3.7 times more likely to be infected with EBV than AP (p = .07; 95% CI: 0.8-16.2). SP were 2.9, 2.1, 3.6, and 1.6 times more likely to be infected with Treponema denticola, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis, respectively. The odds ratio of EBV infecting PP lesions was two times higher in those positive for the virus in saliva. Saliva Tannerella forsythia-positive patients were 15 times more likely to present this pathogen in PP lesions (p = .038). Saliva EBV-positive individuals were 7 and 3.5 times more likely to yield GT contamination with T. forsythia and T. denticola, respectively. EBV copy counts were significantly higher in SP (p < .01). A causal association between EBV, specific bacterial anaerobic infection, and symptomatic PP is likely. EBV high prevalence underscores the viral etiological importance. Salivary EBV contamination is likely to be associated with viral and bacterial GT infection. Saliva PCR analysis can be a good predictor of GT specific infection and help establish antimicrobial therapy. If confirmed by prospective longitudinal clinical trials, antiviral therapy could possibly benefit SP and nonresponsive to treatment individuals and help prevent potential peri-implant infectious complications.

The landscape of host transcriptional response programs commonly perturbed by bacterial pathogens: towards host-oriented broad-spectrum drug targets.

BackgroundThe emergence of drug-resistant pathogen strains and new infectious agents pose major challenges to public health. A promising approach to combat these problems is to target the host’s genes or proteins, especially to discover targets that are effective against multiple pathogens, i.e., host-oriented broad-spectrum (HOBS) drug targets. An important first step in the discovery of such drug targets is the identification of host responses that are commonly perturbed by multiple pathogens.ResultsIn this paper, we present a methodology to identify common host responses elicited by multiple pathogens. First, we identified host responses perturbed by each pathogen using a gene set enrichment analysis of publicly available genome-wide transcriptional datasets. Then, we used biclustering to identify groups of host pathways and biological processes that were perturbed only by a subset of the analyzed pathogens. Finally, we tested the enrichment of each bicluster in human genes that are known drug targets, on the basis of which we elicited putative HOBS targets for specific groups of bacterial pathogens. We identified 84 up-regulated and three down-regulated statistically significant biclusters. Each bicluster contained a group of pathogens that commonly dysregulated a group of biological processes. We validated our approach by checking whether these biclusters correspond to known hallmarks of bacterial infection. Indeed, these biclusters contained biological process such as inflammation, activation of dendritic cells, pro- and anti- apoptotic responses and other innate immune responses. Next, we identified biclusters containing pathogens that infected the same tissue. After a literature-based analysis of the drug targets contained in these biclusters, we suggested new uses of the drugs Anakinra, Etanercept, and Infliximab for gastrointestinal pathogens Yersinia enterocolitica, Helicobacter pylori kx2 strain, and enterohemorrhagic Escherichia coli and the drug Simvastatin for hematopoietic pathogen Ehrlichia chaffeensis.ConclusionsUsing a combination of automated analysis of host-response gene expression data and manual study of the literature, we have been able to suggest host-oriented treatments for specific bacterial infections. The analyses and suggestions made in this study may be utilized to generate concrete hypothesis on which gene sets to probe further in the quest for HOBS drug targets for bacterial infections. All our results are available at the following supplementary website: http://bioinformatics.cs.vt.edu/ murali/supplements/2013-kidane-plos-one

Role of Phenothiazines and Structurally Similar Compounds of Plant Origin in the Fight against Infections by Drug Resistant Bacteria.

Phenothiazines have their primary effects on the plasma membranes of prokaryotes and eukaryotes. Among the components of the prokaryotic plasma membrane affected are efflux pumps, their energy sources and energy providing enzymes, such as ATPase, and genes that regulate and code for the permeability aspect of a bacterium. The response of multidrug and extensively drug resistant tuberculosis to phenothiazines shows an alternative therapy for the treatment of these dreaded diseases, which are claiming more and more lives every year throughout the world. Many phenothiazines have shown synergistic activity with several antibiotics thereby lowering the doses of antibiotics administered to patients suffering from specific bacterial infections. Trimeprazine is synergistic with trimethoprim. Flupenthixol (Fp) has been found to be synergistic with penicillin and chlorpromazine (CPZ); in addition, some antibiotics are also synergistic. Along with the antibacterial action described in this review, many phenothiazines possess plasmid curing activities, which render the bacterial carrier of the plasmid sensitive to antibiotics. Thus, simultaneous applications of a phenothiazine like TZ would not only act as an additional antibacterial agent but also would help to eliminate drug resistant plasmid from the infectious bacterial cells.

Infeções bacterianas no doente com cirrose hepática

Bacterial infections are a frequent complication on hepatic cirrhosis, particularly in hospitalized patients.In this article we review the prevalence, risk factors and pathogenesis of bacterial infections in cirrhotic patients, focusing on the mechanisms of bacterial translocation.The most common bacterial infections in cirrhotic patients are the commonly called “spontaneous” infections, namely spontaneous bacterial peritonitis, spontaneous bacterial pleural empyema and spontaneous bacteraemia.At the end of this article we make a brief reference to the prevention strategies for infection in cirrhosis, namely prophylaxis of spontaneous bacterial peritonitis and prevention of specific viral or bacterial infections through vaccination.