Skin microbiome bacteria enriched following long sun exposure can reduce oxidative damage.

Sun exposure is harmful to the skin and increases the risk of skin aging and skin cancer. Here we examined the effects of daily exposure to sun radiation on the skin microbiome in order to determine whether skim microbiome bacteria can contribute to protection from solar damage. Skin swabs were collected from ten lifeguards before and after the summer to analyse the skin microbiome. The results indicate that specific skin microbiome bacteria were enriched following the seasonal sun exposure. Especially interesting were two bacterial families - Sphingomonas and Erythrobacteraceae - which may have the ability to protect against UV radiation as they produce potentially protective compounds. We concentrated on a Sphingomonas strain and could show that it was highly resistant to UV irradiation and was able to reduce reactive oxygen species levels in human keratinocytes. These results provide a proof-of-concept for the role of the skin microbiome in protection from solar radiation.

Strains Colonizing Different Intestinal Sites within an Individual Are Derived from a Single Founder Population.

Metagenomics has improved our understanding of commensal bacteria that colonize human intestines yet relies almost exclusively on fecal samples. Thus, spatial information about the niche range of these gut microbes and the level of specialized adaptation that they undergo has been inaccessible to fecal metagenomic studies. Here, we leveraged metagenomic data obtained through colonoscopy aspirates from three intestinal sites of healthy adults, and reconstructed metagenome-assembled genomes of several common gut bacteria to address intestinal site-specific evolution. We show that the genomes of bacterial strains at specific intestinal sites are clearly distinct yet are interrelated and are derived from a single founder strain colonizing multiple sites. We also reveal that within those intestinal sites, purifying selection is the dominant evolutionary force acting on Escherichia coli genomes within human hosts. Importantly, no site-specific adaptations at the level of accessory genes were detected, implying that these commensals are well-adapted to several host microniches and can therefore colonize multiple intestinal sites with high efficiency. Nevertheless, bacterial in situ growth rates differ markedly across different sections of the intestine. Metagenomics of aspirate samples can reveal unique strain- and intestinal tissue-specific genomic information. Such information may be critical for understanding bacterial contribution to gastrointestinal diseases, which involve only a part of the intestine, as is often the case in inflammatory bowel disease. IMPORTANCE By reconstructing bacterial genomes from samples taken from specific sites within the human intestines, via aspiration, we show that strains at specific intestinal sites are genetically distinct yet interrelated and are derived from a single founder population. Organ-specific metagenomic information represents a powerful tool to generate insights into gastrointestinal diseases, which involve only a part of the intestine, such as inflammatory bowel disease.

Differences in homologous recombination and maintenance of heteropolyploidy between Haloferax volcanii and Haloferax mediterranei.

Polyploidy, the phenomenon of having more than one copy of the genome in an organism, is common among haloarchaea. While providing short-term benefits for DNA repair, polyploidy is generally regarded as an "evolutionary trap" that by the notion of the Muller's ratchet will inevitably conclude in the species' decline or even extinction due to a gradual reduction in fitness. In most reported cases of polyploidy in archaea, the genetic state of the organism is considered as homoploidy i.e. all copies of the genome are identical. Here we demonstrate that while this is indeed the prevalent genetic status in the halophilic archaeon Haloferax volcanii, its close relative H. mediterranei maintains a prolonged heteroploidy state in a nonselective environment once a second allele is introduced. Moreover, a strong genetic linkage was observed between two distant loci in H. mediterranei indicating a low rate of homologous recombination while almost no such linkage was shown in H. volcanii indicating a high rate of recombination in the latter species. We suggest that H. volcanii escapes Muller's ratchet by means of an effective chromosome-equalizing gene-conversion mechanism facilitated by highly active homologous recombination, whereas H. mediterranei must elude the ratchet via a different, yet to be elucidated mechanism.

Effect of Solar Radiation on Skin Microbiome: Study of Two Populations.

Here, we examined the skin microbiome of two groups of healthy volunteers living on the Mediterranean coast with different exposures to sun radiation. One group, exposed to the sun in the summer, was compared with a group covered with clothing throughout the year. The seasonal effects on the skin microbiome of three body sites were determined before and after summer. Surprisingly, at the phyla level, there were no significant differences in microbiome diversity between the groups. Furthermore, within each group, there were no significant seasonal differences in high-abundance species at any of the sampling sites. These results suggest that the skin microbiome, developed over years, remains stable even after several months of exposure to summer weather, direct sunlight and humidity. However, in the group exposed to the sun during the summer months, there were significant differences in low-abundance species in sun-exposed areas of the skin (the inner and outer arm). These subtle changes in low-abundance species are interesting, and their effect on skin physiology should be studied further.

Escherichia coli Strains from Patients with Inflammatory Bowel Diseases have Disease-specific Genomic Adaptations.

BACKGROUND AND AIMS: Escherichia coli is over-abundant in the gut microbiome of patients with inflammatory bowel disease [IBD]. Here, we aimed to identify IBD-specific genomic functions of diverse E. coli lineages. METHODS: We investigated E. coli genomes from patients with ulcerative colitis [UC], Crohn's disease [CD] or a pouch, and healthy subjects. The majority of genomes were reconstructed from metagenomic samples, including newly sequenced faecal metagenomes. Clinical metadata were collected. Functional analysis at the gene and mutation level were performed and integrated with IBD phenotypes and biomarkers. RESULTS: Overall, 530 E. coli genomes were analysed. The E. coli B2 lineage was more prevalent in UC compared with other IBD phenotypes. Genomic metabolic capacities varied across E. coli lineages and IBD phenotypes. Host mucin utilisation enzymes were present in a single lineage and depleted in patients with a pouch, whereas those involved in inulin hydrolysis were enriched in patients with a pouch. E. coli strains from patients with UC were twice as likely to encode the genotoxic molecule colibactin than strains from patients with CD or a pouch. Strikingly, patients with a pouch showed the highest inferred E. coli growth rates, even in the presence of antibiotics. Faecal calprotectin did not correlate with the relative abundance of E. coli. Finally, we identified multiple IBD-specific non-synonymous mutations in E. coli genes encoding for bacterial cell envelope components. CONCLUSIONS: Comparative genomics indicates that E. coli is a commensal species adapted to the overactive mucosal immune milieu in IBD, rather than causing it. Our results reveal mutations that may lead to attenuated antigenicity in some E. coli strains.

Long-term Antibiotic Treatment in Pouchitis-Patterns of Use and Safety.

INTRODUCTION: Pouchitis, often developing after colectomy and ileal pouch-anal anastomosis for ulcerative colitis, is highly responsive to antibiotics. Ciprofloxacin and/or metronidazole are commonly used, often for prolonged periods. We report patterns of antibiotic use, adverse events, and resistant infections in patients with pouchitis with long-term antibiotic treatment. METHODS: In a cohort of patients following pouch surgery, a retrospective nested case-control analysis was performed between 2010 and 2017. Ultra-long-term use, defined as the top 10% of users, was compared with the remaining users. Patterns of antibiotic use, adverse events, and resistant infections were analyzed. RESULTS: The cohort included 205 patients with UC, of whom 167 (81.5%) used antibiotics for pouchitis, predominantly ciprofloxacin. The long-term antibiotic use rate was 18% and 42% at 5 and 20 years postsurgery, respectively. Mean antibiotic use of at least 1, 3, and 6 months/year was noted in 54 (26.3%), 31 (15.1%), and 14 (6.8%) patients, respectively. Twenty-two (13.2%) and 4 (2.4%) patients reported mild and severe (transient) adverse events, respectively, without mortalities, tendinopathies or arrhythmias. Adverse event rates for ciprofloxacin and metronidazole were 1per 10,000 and 6 per 10,000 use-days, respectively. Longer, but not ultra-long antibiotic use, was associated with mild adverse events. There was no association between antibiotic use and resistant infections. Thirteen (6.3%) patients required ileostomy procedures-more commonly in the ultra-long-term antibiotic users. CONCLUSIONS: Patients with pouchitis may require prolonged antibiotic treatment, reflecting clinical benefit and favorable safety profile. Few adverse events and resistant infections were observed with long-term antibiotics use. However, resistant microbial strains selection, which are potentially transmittable, warrants consideration of different therapeutic alternatives.

Carriage of Colibactin-producing Bacteria and Colorectal Cancer Risk.

Colibactin is a genotoxic molecule, produced primarily by Escherichia coli. Colibactin causes DNA damage that may lead to colorectal cancer. Here we review recent advances in the study of colibactin and propose a focus on patients with inflammatory bowel diseases (IBD) who have higher levels of colibactin-producing bacteria in their intestines.

Predominantly Antibiotic-resistant Intestinal Microbiome Persists in Patients With Pouchitis Who Respond to Antibiotic Therapy.

BACKGROUND & AIMS: Pouchitis that develops in patients with ulcerative colitis after total proctocolectomy and ileal pouch anal anastomosis is usually treated with antibiotics. Some patients have recurrence of flares, or become antibiotic-dependent, and require repeated courses or prolonged periods of antibiotic therapy. We investigated microbial factors associated with response to antibiotic treatment and development of antibiotic dependence in patients with pouchitis. METHODS: We performed a prospective study of 49 patients who had undergone pouch surgery at a tertiary center. Disease activity was determined based on clinical, endoscopic, and histologic criteria. Pouch phenotype was defined as recurrent-acute pouchitis (n = 6), chronic pouchitis and Crohn's-like disease of the pouch (n = 27), normal pouch from patient with ulcerative colitis (n = 10), and normal pouch from patient with familial adenomatous polyposis (n = 6). Fecal samples (n = 234) were collected over time during or in the absence of antibiotic treatment (ciprofloxacin and/or metronidazole). Thirty-three patients were treated with antibiotics, for a median of 425 days of cumulative antibiotic therapy, during follow-up. Calprotectin was measured and fecal DNA was sequenced using shotgun metagenomics and analyzed with specifically designed bioinformatic pipelines. Bacterial strains were isolated from fecal samples. We assessed their ciprofloxacin resistance and ability to induce secretion of inflammatory cytokines by HT-29 intestinal epithelial cells. RESULTS: Most antibiotic-treated patients (79%) had a clinical response to each course of antibiotics; however, 89% of those who completed a 4-week course relapsed within 3 months. Median calprotectin levels decreased by 40% in response to antibiotics. Antibiotic treatment reduced disease-associated bacteria such as Clostridium perfringens, Ruminococcus gnavus, and Klebsiella pneumoniae, but also beneficial species, such as Faecalibacterium prausnitzii. The microbiomes of antibiotic-responsive patients were dominated by facultative anaerobic genera (Escherichia, Enterococcus, and Streptococcus), with multiple ciprofloxacin-resistance mutations in drug target genes and confirmed drug resistance. However, these strains had lower potential for virulence and did not induce secretion of inflammatory cytokines by epithelial cells. After antibiotic cessation, patients had an abrupt shift in microbiome composition, with blooms of oral and disease-associated bacteria. In addition, antibiotic treatment enriched for strains that acquired multidrug resistance loci, encoding enzymes that confer resistance to nonrelated antibiotics, including extended-spectrum beta-lactamases. CONCLUSIONS: The efficacy of antibiotic treatment of pouchitis might be attributed to the establishment of an antibiotic-resistant microbiome with low inflammatory potential. This microbiome might provide resistance against colonization by bacteria that promote inflammation. To avoid progression to antibiotic-dependent disease and its consequences, strategies such as short-term alternating antibiotics and nutrition- and microbiome-based interventions should be considered.

Fecal microbiome signatures of pancreatic cancer patients.

Pancreatic cancer (PC) is a leading cause of cancer-related death in developed countries, and since most patients have incurable disease at the time of diagnosis, developing a screening method for early detection is of high priority. Due to its metabolic importance, alterations in pancreatic functions may affect the composition of the gut microbiota, potentially yielding biomarkers for PC. However, the usefulness of these biomarkers may be limited if they are specific for advanced stages of disease, which may involve comorbidities such as biliary obstruction or diabetes. In this study we analyzed the fecal microbiota of 30 patients with pancreatic adenocarcinoma, 6 patients with pre-cancerous lesions, 13 healthy subjects and 16 with non-alcoholic fatty liver disease, using amplicon sequencing of the bacterial 16S rRNA gene. Fourteen bacterial features discriminated between PC and controls, and several were shared with findings from a recent Chinese cohort. A Random Forest model based on the microbiota classified PC and control samples with an AUC of 82.5%. However, inter-subject variability was high, and only a small part of the PC-associated microbial signals were also observed in patients with pre-cancerous pancreatic lesions, implying that microbiome-based early detection of such lesions will be challenging.

Starch Consumption May Modify Antiglycan Antibodies and Fecal Fungal Composition in Patients With Ileo-Anal Pouch.

BACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by serologic responses to glycans. Patients with ulcerative colitis (UC) after proctocolectomy with ileo-anal anastomosis (pouch surgery) may develop inflammation (pouchitis) that resembles Crohn's disease (CD). We hypothesized that patients' serologic responses were affected by their consumption of dietary sugars. This study analyzed the correlations between antiglycan antibody expression and dietary sugar consumption in patients with UC pouch and the evolution in antibody levels over time. METHODS: Patients were followed prospectively for 2 consecutive visits. The following antiglycan carbohydrate antibodies were detected by enzyme-linked immunosorbent assay: antichitobioside (ACCA), antilaminaribioside (ALCA), antimannobioside (AMCA), and anti-Saccharomyces cerevisiae (ASCA) antibodies. Patients completed a food frequency questionnaire. The fungal community in patients' fecal samples was analyzed by sequencing the internal transcribed spacer 2 (ITS2) region of nuclear ribosomal DNA. RESULTS: We included 75 UC pouch patients aged 45.2 ± 14 years who underwent pouch surgery 9.8 ± 6.7 years previously. Of these patients, 34.7% (n = 26) showed seropositivity for antiglycan antibodies. Starch consumption was significantly higher in patients with positive serologic responses (P = 0.05). Higher starch consumption was associated with higher AMCA and ACCA titers, which increased by 4.08% (0.8%-7.4%; P = 0.014) and 4.8% (0.7%-9.1%; P = 0.007), respectively, for each 10-g increase of dietary starch. The per-patient change in the relative abundance of Candida albicans in fecal samples correlated positively with changes in starch consumption (Spearman's r = 0.72; P = 0.012). CONCLUSIONS: Starch consumption correlated with positive antiglycan serology (ACCA and AMCA), suggesting that increased dietary starch intake may promote a specific immune response in patients with IBD.

The Effect of Density-Dependent Phase on the Locust Gut Bacterial Composition.

The desert locust demonstrates density-dependent phase polyphenism: For extended periods it appears in a non-aggregating, non-migrating phenotype, known as the solitary phase. When circumstances change, solitary individuals may aggregate and transform to the gregarious phenotype, which have a strong propensity for generating large swarms. Previous reports have suggested a role for gut-bacteria derived volatiles in the swarming phenomenon, and suggested that locusts are capable of manipulating their gut microbiome according to their density-dependent phases. Here, we directly tested this hypothesis for the first time. Using locusts of both phases from well-controlled laboratory cultures as well as gregarious field-collected individuals; and high-throughput sequencing. We characterized the hindgut bacterial community composition in the two phases of the desert locust. Our findings demonstrate that laboratory-reared gregarious and solitary locusts maintain a stable core of Enterobacter. However, while different generations of gregarious locust experience shifts in their Enterobacter's relative abundance; the solitary locusts maintain a stable gut microbiome, highly similar to that of the field-collected locusts. Tentative phase differences in wild populations' microbiome may thus be an indirect effect of environmental or other factors that push the swarming individuals to homogenous gut bacteria. We therefore conclude that there are phase-related differences in the population dynamics of the locust hindgut bacterial composition, but there is no intrinsic density-dependent mechanism directly affecting the gut microbiome.

Alterations of Enteric Microbiota in Patients with a Normal Ileal Pouch Are Predictive of Pouchitis.

Objective: To examine whether patients with a mature normal pouch [> 1 year post ileostomy closure] have microbial stool characteristics that can predict pouch inflammation. Design: Patients undergoing pouch surgery were recruited prospectively. Microbiota analysis of faecal samples was by 16S rRNA gene pyrosequencing. All patients had a normal pouch at baseline [T1]. Those without pouchitis during the first year of follow-up [T2] comprised the 'Normal Pouch-sustained' group and those who had experienced an episode of pouchitis comprised the 'Pre-Pouchitis' group. Results: Twenty patients were recruited (age 53.6±13.1 years, pouch age [time from ileostomy closure] 8.1±5.1 years). Seven patients developed pouchitis during follow-up [within 265±93.6 days] and they were assigned to the Pre-Pouchitis group at T1: they had a decreased microbial diversity at T1 compared with the Normal Pouch-sustained patients [n = 13]. The Shannon diversity index for the Pre-Pouchitis patients was 3.4 vs 4.23 for the Normal Pouch-sustained patients [p = 0.011]. There were no substantial group differences in high taxonomic levels [order or above]. The genus Ruminococcus was significantly decreased in the Pre-Pouchitis patients' samples compared with those of the Normal Pouch-sustained patients (0.19% vs 0.78%, respectively, false discovery rate [FDR] = 0.05). The linear discriminant analysis with effect size estimation algorithm revealed that Lachnospira and Coprococcus genera were also decreased among Pre-Pouchitis patients compared with Normal Pouch-sustained patients [0.6% vs 1.95% and 2.1% vs 4%, respectively]. Conclusions: Patients with a normal mature pouch may be predisposed to acute pouchitis when faecal microbial diversity and certain microbial groups are decreased. These findings may aid in risk stratification of those patients.

Impact of a homing intein on recombination frequency and organismal fitness.

Inteins are parasitic genetic elements that excise themselves at the protein level by self-splicing, allowing the formation of functional, nondisrupted proteins. Many inteins contain a homing endonuclease (HEN) domain and rely on its activity for horizontal propagation. However, successful invasion of an entire population will make this activity redundant, and the HEN domain is expected to degenerate quickly under these conditions. Several theories have been proposed for the continued existence of the both active HEN and noninvaded alleles within a population. However, to date, these models were not directly tested experimentally. Using the natural cell fusion ability of the halophilic archaeon Haloferax volcanii we were able to examine this question in vivo, by mating polB intein-positive [insertion site c in the gene encoding DNA polymerase B (polB-c)] and intein-negative cells and examining the dispersal efficiency of this intein in a natural, polyploid population. Through competition between otherwise isogenic intein-positive and intein-negative strains we determined a surprisingly high fitness cost of over 7% for the polB-c intein. Our laboratory culture experiments and samples taken from Israel's Mediterranean coastline show that the polB-c inteins do not efficiently take over an inteinless population through mating, even under ideal conditions. The presence of the HEN/intein promoted recombination when intein-positive and intein-negative cells were mated. Increased recombination due to HEN activity contributes not only to intein dissemination but also to variation at the population level because recombination tracts during repair extend substantially from the homing site.

Distinct Microbiotas are Associated with Ileum-Restricted and Colon-Involving Crohn's Disease.

BACKGROUND: The etiology of inflammatory bowel disease is believed to involve a shift in the microbiota toward more proinflammatory species. Crohn's disease (CD) usually manifests as one of three phenotypes, involving inflammation of the terminal ileum, the colon, or both. However, what determines the particular phenotype and the level of disease activity remains unknown. In this study, we aim to characterize the intestinal microbiota associated with different CD phenotypes. METHODS: DNA was extracted from biopsies of 31 patients with ileal, ileocolic, or colon-restricted CD, and also from 5 non-inflammatory bowel disease control subjects, and analyzed by 16S rRNA gene amplicon pyrosequencing. Data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analyzed using linear discriminant analysis with effect size estimation and PICRUSt algorithms. Two additional recently published cohorts were also analyzed in this study. RESULTS: Highly significant separation was observed between bacterial composition of ileal CD compared with CD with colonic involvement (genus level Bray-Curtis P = 0.005, R = 20%). This separation was unaffected by the biopsy's location or its inflammatory state, or by the patients' condition (remission or relapse). Faecalibacterium was strongly reduced in ileal CD compared with CD with colonic involvement, whereas Enterobacteriaceae were more abundant in the former. Fusobacterium relative abundance was strongly correlated with disease activity in patients with ileal-involving, but not in colon-involving, CD. CONCLUSIONS: Ileal and colon-involving CD sustain distinct microbiotas, suggesting that different mechanisms underlie the two major manifestations of CD. The potential contribution of Fusobacterium to inflammation in ileal CD should be further investigated.

Interactions between the intestinal microbiota and bile acids in gallstones patients.

Cholecystectomy, surgical removal of the gallbladder, changes bile flow to the intestine and can therefore alter the bidirectional interactions between bile acids (BAs) and the intestinal microbiota. We quantified and correlated BAs and bacterial community composition in gallstone patients scheduled for cholecystectomy before and after the procedure, using gas-liquid chromatography and 16S rRNA amplicon sequencing, followed by quantitative real-time polymerase chain reaction of the phylum Bacteroidetes. Gallstone patients had higher overall concentrations of faecal BAs and a decreased microbial diversity, accompanied by a reduction in the beneficial genus Roseburia and an enrichment of the uncultivated genus Oscillospira, compared with controls. These two genera may thus serve as biomarkers for symptomatic gallstone formation. Oscillospira was correlated positively with secondary BAs and negatively with primary BAs, while the phylum Bacteroidetes showed an opposite trend. Cholecystectomy resulted in no substantial change in patients' faecal BAs. However, bacterial composition was significantly altered, with a significant increase in the phylum Bacteroidetes. Given that cholecystectomy has been associated with a higher risk of colorectal cancer and that members of the Bacteroidetes are increased in that disease, microbial consequences of cholecystectomy should be further explored.

Pouch Inflammation Is Associated With a Decrease in Specific Bacterial Taxa.

BACKGROUND & AIMS: Pouchitis is a common long-term complication in patients with ulcerative colitis (UC) undergoing proctocolectomy with ileal pouch-anal anastomosis. Because the inflammation occurs in a previously normal small bowel, studies of this process might provide information about the development of Crohn's disease. Little is known about the intestinal microbiome of patients with pouchitis. We investigated whether specific bacterial populations correlate with the pouch disease phenotype and inflammatory activity. METHODS: We performed a prospective study of patients with UC who underwent pouch surgery (N = 131) from 1981 through 2012 and were followed at Tel Aviv Medical Center. Patients were assigned to groups based on their degree and type of pouch inflammation. Patients with familial adenomatous polyposis after pouch surgery (n = 9), individuals with intact colons undergoing surveillance colonoscopy (n = 10), and patients with UC who did not undergo surgery (n = 9) served as controls. We collected demographic and disease activity data (based on the Pouchitis Disease Activity Index) and measured levels of C-reactive protein. Fecal samples were collected, levels of calprotectin were measured, and microbiota were analyzed by 16S ribosomal RNA gene amplicon pyrosequencing. RESULTS: Increased proportions of the Fusobacteriaceae family correlated with increased disease activity and levels of C-reactive protein in patients with UC who underwent pouch surgery. In contrast, proportions of Faecalibacterium were reduced in patients with pouchitis vs controls; there was a negative correlation between proportion of Faecalibacterium and level of C-reactive protein. There was an association between antibiotic treatment, but not biologic or immunomodulatory therapy, with reduced proportions of 11 genera and with increased proportions of Enterococcus and Enterobacteriaceae. CONCLUSIONS: Reductions in protective bacteria and increases in inflammatory bacteria are associated with pouch inflammation in patients with UC who underwent pouch surgery. The finding that antibiotics exacerbate dysbiosis indicates that these drugs might not provide long-term benefit for patients with pouchitis. Additional studies of this form of dysbiosis could provide information about the pathogenesis of Crohn's disease.

Escherichia coli isolates from patients with bacteremic urinary tract infection are genetically distinct from those derived from sepsis following prostate transrectal biopsy.

BACKGROUND: Transrectal ultrasound-guided (TRUS) prostate biopsy is a very common procedure that is generally considered relatively safe. However, severe sepsis can occur after TRUS prostate biopsies, with Escherichia coli being the predominant causative agent. A common perception is that the bacteria that cause post-TRUS prostate biopsy infections originate in the urinary tract, but this view has not been adequately tested. Yet other authors believe on the basis of indirect evidence that the pathogens are introduced into the bloodstream by the biopsy needle after passage through the rectal mucosa. METHODS: We compared E. coli isolates from male patients with bacteremic urinary tract infection (B-UTI) to isolates of patients with post prostate biopsy sepsis (PPBS), in terms of their sequence types, determined by multi-locus sequence typing (MLST) and their virulence markers. RESULTS: B-UTI isolates were much richer in virulence genes than were PPBS isolates, supporting the hypothesis that E. coli causing PPBS derive directly from the rectum. Sequence type 131 (ST131) strains and related strain from the ST131 were common (>30%) among the E. coli isolates from PPBS patients as well as from B-UTI patients and all these strains expressed extended spectrum beta-lactamases. CONCLUSIONS: Our finding supports the hypothesis that E. coli causing PPBS derive directly from the rectum, bypassing the urinary tract, and therefore do not require many of the virulence capabilities necessary for an E. coli strain that must persist in the urinary tract. In light of the increasing prevalence of highly resistant E. coli strains, a new approach for prevention of PPBS is urgently required.

Maximal sum of metabolic exchange fluxes outperforms biomass yield as a predictor of growth rate of microorganisms.

Growth rate has long been considered one of the most valuable phenotypes that can be measured in cells. Aside from being highly accessible and informative in laboratory cultures, maximal growth rate is often a prime determinant of cellular fitness, and predicting phenotypes that underlie fitness is key to both understanding and manipulating life. Despite this, current methods for predicting microbial fitness typically focus on yields [e.g., predictions of biomass yield using GEnome-scale metabolic Models (GEMs)] or notably require many empirical kinetic constants or substrate uptake rates, which render these methods ineffective in cases where fitness derives most directly from growth rate. Here we present a new method for predicting cellular growth rate, termed SUMEX, which does not require any empirical variables apart from a metabolic network (i.e., a GEM) and the growth medium. SUMEX is calculated by maximizing the SUM of molar EXchange fluxes (hence SUMEX) in a genome-scale metabolic model. SUMEX successfully predicts relative microbial growth rates across species, environments, and genetic conditions, outperforming traditional cellular objectives (most notably, the convention assuming biomass maximization). The success of SUMEX suggests that the ability of a cell to catabolize substrates and produce a strong proton gradient enables fast cell growth. Easily applicable heuristics for predicting growth rate, such as what we demonstrate with SUMEX, may contribute to numerous medical and biotechnological goals, ranging from the engineering of faster-growing industrial strains, modeling of mixed ecological communities, and the inhibition of cancer growth.

DNA as a phosphate storage polymer and the alternative advantages of polyploidy for growth or survival.

Haloferax volcanii uses extracellular DNA as a source for carbon, nitrogen, and phosphorous. However, it can also grow to a limited extend in the absence of added phosphorous, indicating that it contains an intracellular phosphate storage molecule. As Hfx. volcanii is polyploid, it was investigated whether DNA might be used as storage polymer, in addition to its role as genetic material. It could be verified that during phosphate starvation cells multiply by distributing as well as by degrading their chromosomes. In contrast, the number of ribosomes stayed constant, revealing that ribosomes are distributed to descendant cells, but not degraded. These results suggest that the phosphate of phosphate-containing biomolecules (other than DNA and RNA) originates from that stored in DNA, not in rRNA. Adding phosphate to chromosome depleted cells rapidly restores polyploidy. Quantification of desiccation survival of cells with different ploidy levels showed that under phosphate starvation Hfx. volcanii diminishes genetic advantages of polyploidy in favor of cell multiplication. The consequences of the usage of genomic DNA as phosphate storage polymer are discussed as well as the hypothesis that DNA might have initially evolved in evolution as a storage polymer, and the various genetic benefits evolved later.

Gastric microbiota is altered in oesophagitis and Barrett's oesophagus and further modified by proton pump inhibitors.

Gastro-oesophageal reflux can cause inflammation, metaplasia, dysplasia and cancer of the oesophagus. Despite the increased use of proton pump inhibitors (PPIs) to treat reflux, the incidence of oesophageal adenocarcinoma has increased rapidly in Europe and in the United States in the last 25 years. The reasons for this increase remain unclear. In this study, we aimed to determine whether the microbiota of the gastric refluxate and oesophageal biopsies differs between patients with heartburn and normal-appearing oesophageal mucosa versus patients with abnormal oesophageal mucosa [oesophagitis or Barrett's oesophagus (BE)] and to elucidate the effect of PPIs on the bacterial communities using 16S rRNA gene pyrosequencing. Significant differences in the composition of gastric fluid bacteria were found between patients with heartburn and normal oesophageal tissue versus patients with oesophagitis or BE, but in the oesophagus-associated microbiota differences were relatively modest. Notably, increased levels of Enterobacteriaceae were observed in the gastric fluid of oesophagitis and BE patients. In addition, treatment with PPIs had dramatic effects on microbial communities both in the gastric fluids and the oesophageal tissue. In conclusion, gastric fluid microbiota is modified in patients with oesophagitis and BE compared with heartburn patients with normal biopsies. Furthermore, PPI treatment markedly alters gastric and oesophageal microbial populations. Determining whether the changes in bacterial composition caused by PPIs are beneficial or harmful will require further investigation.