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ABSTRACTDysbiosis of the gut microbiome and a pathological immune response in intestinal tissues form the basis of Crohn’s disease (CD), which is a debilitating disease with relevant morbidity and mortality. It is increasing in childhood and adolescents, due to western life-style and nutrition and a large set of predisposing genetic factors. Crohn’s disease-associated genetic mutations play an essential role in killing pathogens, altering mucosal barrier function, and protecting the host microbiome, suggesting an important pathogenic link. The intestinal microbiome is highly variable and can be influenced by environmental factors. Changes in microbial composition and a reduction in species diversity have been shown to be central features of disease progression and are therefore the target of therapeutic approaches. In this review, we summarize the current literature on the role of the gut microbiome in childhood, adolescent, and adult CD, current therapeutic options, and their impact on the microbiome.

Abstract Perianal abscesses are frequent diseases in general surgery. Principles of standard patient care are surgical drainage with exploration and concomitant treatment of fistula. Antiinfective therapy is frequently applied in cases of severe local disease and perianal sepsis. However, the role of microbiologic testing of purulence from perianal abscesses is disputed and the knowledge concerning bacteriology and bacterial resistances is very limited. A retrospective cohort study was performed of consecutive patients (≥ 12 years of age) from a tertiary care hospital, who underwent surgical treatment for perianal abscess from 01/2008 to 12/2019. Subdividing the cohort into three groups regarding microbiological testing results: no microbiological testing of purulence (No_Swab, n = 456), no detection of drug resistant bacteria [DR(−), n = 141] or detection of bacteria with acquired drug resistances from purulence [DR(+), n = 220]. Group comparisons were performed using Kruskall–Wallis test and, if applicable, followed by Dunn´s multiple comparisons test for continuous variables or Fishers exact or Pearson’s X2 test for categorical data. Fistula persistence was estimated by Kaplan Meier and compared between the groups using Log rank test. Corralation analysis between perioperative outcome parameters and bacteriology was performed using Spearman´s rho rank correlation. Higher pretherapeutic C-reactive protein (p

Mycobacterium genavense infection, a rare nontuberculous mycobacteria infection, occurs in heavily immunocompromised patients (i.e., those with advanced HIV disease, genetic disorders, or acquired immunologic disorders and those undergoing immunosuppressive therapy). We report a case of disseminated M. genavense infection preceding Hodgkin lymphoma in a patient without obvious risk factors for this infection.

Abstract Whole-genome sequencing analysis of Vancomycin-resistant Enterococcus faecium isolates from the Frankfurt metropolitan region revealed that 78/94 isolates were MLST type ST117, cgMLST complex type CT71 with a common vanB chromosomal insertion site. This indicates circulation of a single VRE clone in a catchment area of 5,000-km2 with 3 million inhabitants.

Summary: Background: Vancomycin-resistant Enterococcus faecium (VREfm) are an emerging threat worldwide. In Germany, a VRE-belt with higher VREfm prevalences transversing its central east-west axis and including the state of Hesse was previously described. Recently, we detected a predominant VREfm clone in hospitals throughout the Rhine-Main metropolitan area of Hesse. Aim: Here we expanded our study on VREfm to a regional neurological acute hospital outside of the metropolitan area with patient referrals from throughout Hesse and the neighboring federal state of Rhineland-Palatinate. Material/Methods: VREfm isolates obtained between 2016-2018 from a regional neurological acute hospital with intensive care and early rehabilitation units were investigated (n=55). Patient data was collected and analyzed together with whole-genome sequencing data to investigate antibiotic resistance and virulence determinants of the VREfm. The population structure of VREfm was investigated using the Core genome-based multilocus sequence typing (cgMLST). Findings: The average age of the patients was 67.1 years. For 96% of the patients, a previous hospital stay was reported. 64% of the patients were treated with antibiotics. All VREfm harbored the vanB vancomycin resistance gene. The multilocus sequence types (STs) detected changed abruptly from four different STs in 2016 to a predominant ST in 2017 and 2018 (ST117). Most of the ST117 isolates were members of the cgMLST type CT71. Conclusion: The results indicate a sudden shift of the VREfm population structure from a semi-heterogeneous population to a pre-dominant clone within an interval of two years. Further investigations are warranted to understand the epidemiology and emergence of this clone.

[This corrects the article DOI: 10.1371/journal.pntd.0005028.].

Whole genome sequencing of bacteria has become daily routine in many fields. Advances in DNA sequencing technologies and continuously dropping costs have resulted in a tremendous increase in the amounts of available sequence data. However, comprehensive in-depth analysis of the resulting data remains an arduous and time-consuming task. In order to keep pace with these promising but challenging developments and to transform raw data into valuable information, standardized analyses and scalable software tools are needed. Here, we introduce ASA3P, a fully automatic, locally executable and scalable assembly, annotation and analysis pipeline for bacterial genomes. The pipeline automatically executes necessary data processing steps, i.e. quality clipping and assembly of raw sequencing reads, scaffolding of contigs and annotation of the resulting genome sequences. Furthermore, ASA3P conducts comprehensive genome characterizations and analyses, e.g. taxonomic classification, detection of antibiotic resistance genes and identification of virulence factors. All results are presented via an HTML5 user interface providing aggregated information, interactive visualizations and access to intermediate results in standard bioinformatics file formats. We distribute ASA3P in two versions: a locally executable Docker container for small-to-medium-scale projects and an OpenStack based cloud computing version able to automatically create and manage self-scaling compute clusters. Thus, automatic and standardized analysis of hundreds of bacterial genomes becomes feasible within hours. The software and further information is available at: asap.computational.bio.

We examined extended-spectrum β-lactamase–producing isolates from livestock, humans, companion animals, food, and the environment during 2009–2016 in Germany for the presence of CTX-M-27 allele within Escherichia coli sequence type (ST) 131. E. coli ST131 C1-M27 was exclusively present in humans; its incidence increased from 0% in 2009 to 45% in 2016.

The reassessment of known but neglected natural compounds is a vital strategy for providing novel lead structures urgently needed to overcome antimicrobial resistance. Scaffolds with resistance-breaking properties represent the most promising candidates for a successful translation into future therapeutics. Our study focuses on chelocardin, a member of the atypical tetracyclines, and its bioengineered derivative amidochelocardin, both showing broad-spectrum antibacterial activity within the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) panel. Further lead development of chelocardins requires extensive biological and chemical profiling to achieve favorable pharmaceutical properties and efficacy. This study shows that both molecules possess resistance-breaking properties enabling the escape from most common tetracycline resistance mechanisms. Further, we show that these compounds are potent candidates for treatment of urinary tract infections due to their in vitro activity against a large panel of multidrug-resistant uropathogenic clinical isolates. In addition, the mechanism of resistance to natural chelocardin was identified as relying on efflux processes, both in the chelocardin producer Amycolatopsis sulphurea and in the pathogen Klebsiella pneumoniae. Resistance development in Klebsiella led primarily to mutations in ramR, causing increased expression of the acrAB-tolC efflux pump. Most importantly, amidochelocardin overcomes this resistance mechanism, revealing not only the improved activity profile but also superior resistance-breaking properties of this novel antibacterial compound.

Strain E19T described as Hartmannibacter diazotrophicus gen. nov. sp. nov. was isolated from the rhizosphere of Plantago winteri from a natural salt meadow in a nature protection area. Strain E19T is a plant growth-promoting rhizobacterium able to colonize the rhizosphere of barley and to promote its growth only under salt stress conditions. To gain insights into the genetic bases of plant growth promotion and its lifestyle at the rhizosphere under salty conditions, we determined the complete genome sequence using two complementary sequencing platforms (Ilumina MiSeq and PacBio RSII). The E19T genome comprises one circular chromosome and one plasmid containing several genes involved in salt adaptation and genes related to plant growth-promoting traits under salt stress. Based on previous experiments, ACC deaminase activity was identified as a main mechanism of E19T to promote plant growth under salt stress. Interestingly, no genes classically reported to encode for ACC deaminase activity are present. In general, the E19T genome provides information to confirm, discover, and better understand many of its previously evaluated traits involved in plant growth promotion under salt stress. Furthermore, the complete E19T genome sequence helps to define its previously reported unclear 16S rRNA gene-based phylogenetic affiliation. Hartmannibacter forms a distinct subcluster with genera Methylobrevis, Pleomorphomonas, Oharaeibacter, and Mongoliimonas subclustered with genera belonging to Rhizobiales.

Details about the members of the Indian Listeria Consortium are provided in the Supplementary Data.Emerging Microbes and Infections (2016) 5, e55; doi:10.1038/emi.2016.55; published online 8 June 2016

BACKGROUND:Cutaneous dirofilariosis is a canine mosquito-borne zoonosis that can cause larva migrans disease in humans. Dirofilaria repens is considered an emerging pathogen occurring with high prevalence in Mediterranean areas and many parts of tropical Asia. In Hong Kong, a second species, Candidatus Dirofilaria hongkongensis, has been reported. The present study aimed to compare mitochondrial genomes from these parasites and to obtain population genetic information. METHODS AND FINDINGS:Complete mitochondrial genomes were obtained by PCR and Sanger sequencing or ILLUMINA sequencing for four worms. Cytochrome oxidase subunit 1 sequences identified three as D. repens (all from Europe) and one as C. D. hongkongensis (from India). Mitochondrial genomes have the same organization as in other spirurid nematodes but a higher preference for thymine in the coding strand. Phylogenetic analysis was in contradiction to current taxonomy of the Onchocercidae but in agreement with a recent multi-locus phylogenetic analysis using both mitochondrial and nuclear markers. D. repens and C. D. hongkongensis sequences clustered together and were the common sister group to Dirofilaria immitis. Analysis of a 2.5 kb mitochondrial genome fragment from macrofilaria or canine blood samples from Europe (42), Thailand (2), India (1) and Vietnam (1) revealed only small genetic differences in the D. repens samples including all European and the Vietnam sample. The Indian C. D. hongkongensis and the two Thai samples formed separate clusters and differences were comparatively large. CONCLUSION:Genetic differences between Dirofilaria spp. causing cutaneous disease can be considerable whereas D. repens itself was genetically quite homogenous. C. D. hongkongensis was identified for the first time from the Indian subcontinent. The full mitochondrial genome sequence strengthens the hypothesis that it represents an independent species and the Thai samples might represent another cryptic species, Candidatus Dirofilaria sp. 'Thailand II', or a quite divergent population of C. D. hongkongensis.

Diffuse unilateral subacute neuroretinitis is an ocular infectious disease caused by several distinct nematodes. Definite identification of the involved nematodes is rarely achieved. We report on the molecular-based genetic identification of an Ancylostoma ceylanicum hookworm implicated in a case of diffuse unilateral subacute neuroretinitis in a child.