Colon impairments and inflammation driven by an altered gut microbiota leads to social behavior deficits rescued by hyaluronic acid and celecoxib.

BACKGROUND: The exact mechanisms linking the gut microbiota and social behavior are still under investigation. We aimed to explore the role of the gut microbiota in shaping social behavior deficits using selectively bred mice possessing dominant (Dom) or submissive (Sub) behavior features. Sub mice exhibit asocial, depressive- and anxiety-like behaviors, as well as systemic inflammation, all of which are shaped by their impaired gut microbiota composition. METHODS: An age-dependent comparative analysis of the gut microbiota composition of Dom and Sub mice was performed using 16S rRNA sequencing, from early infancy to adulthood. Dom and Sub gastrointestinal (GI) tract anatomy, function, and immune profiling analyses were performed using histology, RT-PCR, flow cytometry, cytokine array, and dextran-FITC permeability assays. Short chain fatty acids (SCFA) levels in the colons of Dom and Sub mice were quantified using targeted metabolomics. To support our findings, adult Sub mice were orally treated with hyaluronic acid (HA) (30 mg/kg) or with the non-steroidal anti-inflammatory agent celecoxib (16 mg/kg). RESULTS: We demonstrate that from early infancy the Sub mouse gut microbiota lacks essential bacteria for immune maturation, including Lactobacillus and Bifidobacterium genera. Furthermore, from birth, Sub mice possess a thicker colon mucin layer, and from early adulthood, they exhibit shorter colonic length, altered colon integrity with increased gut permeability, reduced SCFA levels and decreased regulatory T-cells, compared to Dom mice. Therapeutic intervention in adult Sub mice treated with HA, celecoxib, or both agents, rescued Sub mice phenotypes. HA treatment reduced Sub mouse gut permeability, increased colon length, and improved mouse social behavior deficits. Treatment with celecoxib increased sociability, reduced depressive- and anxiety-like behaviors, and increased colon length, and a combined treatment resulted in similar effects as celecoxib administered as a single agent. CONCLUSIONS: Overall, our data suggest that treating colon inflammation and decreasing gut permeability can restore gut physiology and prevent social deficits later in life. These findings provide critical insights into the importance of early life gut microbiota in shaping gut immunity, functionality, and social behavior, and may be beneficial for the development of future therapeutic strategies.

Extended spectrum ß lactamase-producing Enterobacteriaceae shedding by race horses in Ontario, Canada.

BACKGROUND: We aimed to investigate the prevalence, molecular epidemiology and prevalence factors for Extended Spectrum ß-Lactamase-producing Enterobacteriaceae (ESBL-E) shedding by race horses. A cross-sectional study was performed involving fecal samples collected from 169 Thoroughbred horses that were housed at a large racing facility in Ontario, Canada. Samples were enriched, plated on selective plates, sub-cultured to obtain pure cultures and ESBL production was confirmed. Bacterial species were identified and antibiotic susceptibility profiles were assessed. E. coli sequence types (ST) and ESBL genes were determined using multilocus sequence type (MLST) and sequencing. Whole genome sequencing was performed to isolates harboring CTX-M-1 gene. Medical records were reviewed and associations were investigated. RESULTS: Adult horses (n = 169), originating from 16 different barns, were sampled. ESBL-E shedding rate was 12% (n = 21/169, 95% CI 8-18%); 22 ESBL-E isolates were molecularly studied (one horse had two isolates). The main species was E. coli (91%) and the major ESBL gene was CTX-M-1 (54.5%). Ten different E. coli STs were identified. Sixty-four percent of total isolates were defined as multi-drug resistant. ESBL-E shedding horses originated from 8/16 different barns; whereas 48% (10/21) of them originated from one specific barn. Overall, antibiotic treatment in the previous month was found as a prevalence factor for ESBL-E shedding (p = 0.016, prevalence OR = 27.72, 95% CI 1.845-416.555). CONCLUSIONS: Our findings demonstrate the potential diverse reservoir of ESBL-E in Thoroughbred race horses. Multi-drug resistant bacteria should be further investigated to improve antibiotic treatment regimens and equine welfare.

Risk analysis of antimicrobial resistance in outpatient urinary tract infections of young healthy adults.

Objectives: Most studies addressing community-acquired urinary tract infections (UTIs) pertain to mixed cohorts, in which young healthy adults are under-represented. We aimed to dissect the intricate interrelation between exposures and subsequent antimicrobial resistance (AMR) patterns in a unique setting of young healthy adults, allowing further guidance in this group. Methods: We carried out a retrospective cross-sectional study of all Enterobacteriaceae-associated outpatient UTIs during 2014-16 in soldiers, representing the young fit population in Israel. Electronic medical records were reviewed for demographic and clinical data, antimicrobial exposures and prescriptions. Risk factors for AMR were analysed by multivariate logistic regression. Results: Of 1207 cases, 1144 (94.8%) were females, with a median age of 20.2 years. Escherichia coli was the predominant species (83.2%). Only 686 (56.8%) isolates were fully susceptible. AMR rates were as follows: trimethoprim/sulfamethoxazole, 19.6%; oral cephalosporins, 9.7%-16.7%; amoxicillin/clavulanate, 12.1%; ciprofloxacin, 11.1%; and nitrofurantoin, 12.6%. Predictors of AMR were recurrent UTIs, past-year hospitalization, male gender and non E. coli strains. Antimicrobials prescribed >6 months preceding the culprit infection were not related to AMR. Fluoroquinolone and cephalosporin exposures were highly predictive of further AMR, yet nitrofurantoin and, to a lesser extent, amoxicillin/clavulanate had fewer associations with AMR induction and resistance to these antimicrobials was less associated with any exposure. Conclusions: This nationwide study of community-related UTIs shows significant AMR rates for commonly used oral antimicrobials even in young fit adults. Nitrofurantoin proved once more to be an adequate empirical choice regardless of previous exposures, having a less detrimental effect on future AMR. Conversely, both resistance to fluoroquinolones following previous exposures and the associated heavy ecological burden should deter their common use as first-line agents for UTIs.

Plasma Activation of a Breast Implant Shell in Conjunction With Antibacterial Irrigants Enhances Antibacterial Activity.

BACKGROUND: Infection and capsular contracture are two of the most significant complications of breast-implant surgery. Both complications are associated with bacterial contamination of the implant surface. Plasma activation of the surface of a silicone breast implant changes its surface properties from water repelling (hydrophobic) to water absorbing (hydrophilic), thus making it possible for antibacterial irrigants to temporarily adsorb onto the implant surface. OBJECTIVES: To support our hypothesis that by changing the surface properties we could render antibacterial irrigation more effective in inhibiting bacterial growth on a breast implant shell. METHODS: An in vitro study using silicone discs cut from a textured silicone breast implant shell was performed by treating some of the discs with plasma activation and then exposing the discs to contamination with either Staphylococcus aureus or Pseudomonas aeruginosa and then variously treating the discs with 10% povidone iodine, Cefazolin, or Gentamicin. Bacterial contamination was verified and counted using contact plates as well as culture media. RESULTS: Plasma activation changed the wetting properties of the disc's surface from hydrophobic to hydrophilic. Nonplasma activated contaminated discs demonstrated clear bacterial growth both in the untreated group and in the antibacterial-treated group. Combining antibacterial treatment with plasma activation resulted in complete inhibition of bacterial growth in each of the groups treated with antibacterial irrigants. CONCLUSIONS: Combining plasma activation with topical antibacterial irrigants can inhibit the growth of bacteria on implant shell discs. By changing the properties of the surface from hydrophobic to hydrophilic, the adsorption of the antibacterial irrigants is enhanced.

Efficacy of dalbavancin in the treatment of MRSA rat sternal osteomyelitis with mediastinitis.

OBJECTIVES: Dalbavancin, a semi-synthetic lipoglycopeptide, is characterized by a long plasma half-life, which allows weekly dosing. Dalbavancin may be a good treatment option for patients with deep sternal wound infections owing to its improved pharmacokinetic profile and antibacterial activity compared with currently used antibiotics. Here we evaluated the efficacy of 7 or 14 days of treatment with dalbavancin, compared with vancomycin and with saline, in reducing sternal bone MRSA counts in a rat Staphylococcus aureus deep sternal wound infection model. METHODS: A mid-sternal wound was surgically induced in anaesthetized rats. A clinical strain of MRSA was injected into the sternum to establish infection. Rats were treated intraperitoneally for 7 or 14 days with dalbavancin, vancomycin or saline. The number of cfu per gram of sternum or spleen tissue was determined using viable counts. The antibacterial efficacy was determined by the reduction in bacterial counts per gram of sternum or spleen tissue in each treatment group. RESULTS: Treatment with dalbavancin was superior to treatment with saline for 7 days (0.75 log reduction in bone cfu) or 14 days (>3 log reduction in bone cfu) and similar to treatment with vancomycin. Additionally, dalbavancin was also effective in reducing systemic dissemination of MRSA. CONCLUSIONS: Dalbavancin is effective in the treatment of MRSA rat sternal osteomyelitis.

Persistence of Klebsiella pneumoniae ST258 as the predominant clone of carbapenemase-producing Enterobacteriaceae in post-acute-care hospitals in Israel, 2008-13.

OBJECTIVES: To study the molecular characteristics of carbapenemase-producing Enterobacteriaceae (CPE) in post-acute-care hospitals (PACHs) in Israel and to analyse the temporal changes between 2008 and 2013. METHODS: CPE isolates were obtained during two cross-sectional, point prevalence national surveys of PACHs in Israel performed in 2008 and 2013. Surveillance cultures were collected by streaking rectal swabs onto selective media. Isolates were identified to species level and tested for blaKPC, blaNDM and blaOXA-48 by PCR and by the Carba NP test. Molecular typing was done by PCR for the pilv-l gene, designed for the ST258 KPC-producing Klebsiella pneumoniae (KPC-KP) clone, BOX-PCR and MLST. RESULTS: The prevalence of CPE carriage in the first survey was 184/1147 (16%); all of the isolates were KPC-KP. The prevalence of CPE carriage in the second survey was 127/1287 (9.9%); of these isolates, 113 (89%) were KPC-KP, 9 (7%) were other KPC-producing species and 5 (4%) were NDM- and OXA-48-producing CPE (n = 1 and 4, respectively). The proportion of the KPC-KP population represented by the ST258 clone increased from 120/184 (65%) in 2008 to 91/113 (80%) in 2013. In 58% (71/122) of the KPC-CPE carriers identified in the 2013 survey, the source of acquisition was determined to be the PACH itself. All four OXA-48 CPE were acquired either directly or indirectly from patients arriving from the Palestinian Authority or Syria. CONCLUSIONS: Despite the decreased prevalence of CPE in Israeli PACHs, and the emergence of new types of CPE, the KPC-KP ST258 clone remains the predominant clone represented.

Persistence and complex evolution of fluoroquinolone-resistant Streptococcus pneumoniae clone.

Prolonged outbreaks of multidrug-resistant Streptococcus pneumoniae in health care facilities are uncommon. We found persistent transmission of a fluroquinolone-resistant S. pneumoniae clone during 2006-2011 in a post-acute care facility in Israel, despite mandatory vaccination and fluoroquinolone restriction. Capsular switch and multiple antimicrobial nonsusceptibility mutations occurred within this single clone. The persistent transmission of fluoroquinolone-resistant S. pneumoniae during a 5-year period underscores the importance of long-term care facilities as potential reservoirs of multidrug-resistant streptococci.

Biofilm formation and susceptibility to gentamicin and colistin of extremely drug-resistant KPC-producing Klebsiella pneumoniae.

OBJECTIVES: KPC-producing Klebsiella pneumoniae (KPC-Kpn) is a worldwide challenging pathogen, yet its biofilm-forming potential is not defined. We characterized biofilm formation of this pathogen and determined biofilm susceptibility to gentamicin and colistin. METHODS: Forty-six KPC-Kpn clinical isolates were studied [sequence type (ST) 258, n = 28; and other STs, n = 18]. Biofilm biomass was determined using the standard assay measured by OD590 (where OD stands for optical density) and visualized using confocal microscopy. Antibiotic effect on biofilm formation was evaluated and susceptibility within biofilm was determined by the minimal biofilm elimination concentration (MBEC) method. RESULTS: KPC-Kpn isolates produced biofilm in the range of 0.02-0.3 OD590, where ST258 isolates produced less biofilm compared with other STs (median OD590 0.07 versus 0.15, respectively; P < 0.05). Biofilm biovolumes were in the range of 354 ± 323 to 27,461.4 ± 11,886.7 µm(3). In the planktonic state, ST258 isolates were less resistant to gentamicin compared with other STs (resistance rates: 14% versus 66%, respectively; P < 0.05). Gentamicin-resistant isolates (MIC ≥ 32 mg/L) showed a dramatic increase in resistance within the biofilm (up to 234-fold), whereas gentamicin-susceptible isolates (MIC <32 mg/L) retained their susceptibility. The elevated gentamicin resistance was not due to overexpression of the aminoglycoside resistance gene aac(3)-II in the biofilm state. Resistance to colistin in biofilm increased as well, but was less prominent (P < 0.05). Biofilm biomass did not affect the MBECs of gentamicin and colistin, regardless of the genetic lineage. CONCLUSIONS: KPC-Kpn and particularly ST258 do not form massive biofilms. Nevertheless, susceptibility to gentamicin of this endemic lineage is retained in its biofilm state, supporting the use of this antibiotic in the clinical scenario.

Prevalence and Molecular Characterization of Extended-Spectrum ß-Lactamase Producing Enterobacterales in Healthy Community Dogs in Israel.

BACKGROUND: antimicrobial resistance is a global problem in human and veterinary medicine. We aimed to investigate the extended spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) gut colonization in healthy community dogs in Israel. METHODS: Rectal swabs were sampled from 145 healthy dogs, enriched, plated on selective plates, sub-cultured to obtain pure cultures, and ESBL production was confirmed. Bacterial species and antibiotic susceptibility profiles were identified. WGS was performed on all of the ESBL-PE isolates and their resistomes were identified in silico. Owners' questionnaires were collected for risk factor analysis. RESULTS: ESBL-PE gut colonization rate was 6.2% (n = 9/145, 95% CI 2.9-11.5). Overall, ten isolates were detected (one dog had two isolates); the main species was Escherichia coli (eight isolates), belonging to diverse phylogenetic groups-B1, A and C. Two isolates were identified as Citrobacter braakii, and C. portucalensis. A phylogenetic analysis indicated that all of the isolates were genetically unrelated and sporadic. The isolates possessed diverse ESBL genes and antibiotic-resistance gene content, suggesting independent ESBL spread. In a multivariable risk factor analysis, coprophagia was identified as a risk factor for ESBL-PE gut colonization (p = 0.048, aOR = 4.408, 95% CI 1.014-19.169). CONCLUSIONS: healthy community dogs may be colonized with ESBL-PE MDR strains, some of which were previously reported in humans, that carry wide and diverse resistomes and may serve as a possible source for AMR.

High prevalence of methicillin-resistant Staphylococcus aureus among residents and staff of long-term care facilities, involving joint and parallel evolution.

Six long-term care facilities were surveyed for methicillin-resistant Staphylcoccus aureus (MRSA). Among 191 residents, 14% were carriers; 1 strain predominated (ST5-SCCmec II). Among 132 staff members, 11% were positive; 2 strains predominated (ST5-SCCmec II, ST8-SCCmec IV). All strains were Panton-Valentine leukocidin-negative. The epidemiology of MRSA among residents and staff involved joint and parallel evolution.

Outbreak of colistin-resistant, carbapenem-resistant Klebsiella pneumoniae in metropolitan Detroit, Michigan.

Carbapenem-resistant Klebsiella pneumoniae has spread worldwide and throughout the United States. Colistin is used extensively to treat infections with this organism. We describe a cluster of colistin-resistant, carbapenem-resistant K. pneumoniae infection cases involving three institutions in Detroit, MI. A cluster of five cases of colistin-resistant, carbapenem-resistant K. pneumoniae was identified at Detroit Medical Center (DMC) from 27 July to 22 August 2009. Epidemiologic data were collected, and transmission opportunities were analyzed. Isolates were genotyped by using pulsed-field gel electrophoresis and repetitive extragenic palindromic PCR. Data regarding the use of colistin were obtained from pharmacy records. The index case of colistin-resistant, carbapenem-resistant K. pneumoniae was followed 20 days later by four additional cases occurring in a 6-day interval. All of the patients, at some point, had stayed at one particular institution. The mean number of opportunities for transmission between patients was 2.3 ± 0.5, and each patient had at least one opportunity for transmission with one of the other patients. Compared to 60 colistin-susceptible, carbapenem-resistant K. pneumoniae controls isolated in the previous year at DMC, case patients were significantly older (P = 0.05) and the carbapenem-resistant K. pneumoniae organisms isolated from them displayed much higher MICs to imipenem (P < 0.001). Colistin use was not enhanced in the months preceding the outbreak. Genotyping revealed two closely related clones. This report of a colistin-resistant, carbapenem-resistant K. pneumoniae outbreak is strongly linked to patient-to-patient transmission. Controlling the spread and novel emergence of bacteria with this phenotype is of paramount importance.

Laboratory and clinical evaluation of screening agar plates for detection of carbapenem-resistant Enterobacteriaceae from surveillance rectal swabs.

The increased worldwide spread of carbapenem-resistant Enterobacteriaceae (CRE) emphasizes the need for a sensitive screening procedure to identify these microorganisms. Gastrointestinal carriers may serve as the reservoir for cross-transmission in the health care setting, and thus active surveillance is a key part in preventing the spread of such strains. Three agar-based methods for direct CRE detection from rectal swabs were compared: CHROMagar-KPC (Chrom); MacConkey agar with imipenem at 1 µg/ml (MacI); and MacConkey plates with imipenem, meropenem, and ertapenem disks (MacD). First, we compared the levels of detection (LODs) of 10 molecularly characterized carbapenemase-producing Enterobacteriaceae strains by the three methods. Second, we compared their performance in a surveillance study using rectal swabs (n = 139). The LODs of carbapenemase-producing Enterobacteriaceae strains were influenced by their MICs to carbapenems and were best for MacI, followed by Chrom. The MacD method was able to detect only the strains exhibiting MICs of ≥ 32 µg/ml to at least ertapenem. In the surveillance study, both Chrom and MacI had greater sensitivity (85%) than MacD (76%). However, MacI was the most specific method. In conclusion, MacI appears to be most appropriate medium for the detection of CRE in settings in which multiclonal CRE strains with various MICs to carbapenems are circulating.

Introduction of OXA-48-producing Enterobacteriaceae to Israeli hospitals by medical tourism.

OBJECTIVES: The carbapenemase OXA-48 has been reported from different Mediterranean countries. It is mostly encoded on a single plasmid in various Enterobacteriaceae species. We characterized the epidemiological and molecular features of OXA-48-producing Enterobacteriaceae (OPE) in Israel. METHODS: Epidemiological investigation was conducted by the National Center for Infection Control. Genotyping was performed using multilocus sequence typing. The bla(OXA-48)-carrying plasmids were investigated using S1 endonuclease and restriction fragment length polymorphism (RFLP). Conjugation efficiency of the bla(OXA-48)-carrying plasmids was studied in a filter mating experiment. RESULTS: Since 2007, four OPE-infected patients were identified, all non-Israeli (two Palestinian, one Jordanian and one Georgian). Three had prior hospitalization; two in Jordan and one in Georgia. The bla(OXA-48) gene was detected in three Escherichia coli strains belonging to different clonal complexes, one Klebsiella oxytoca and one Klebsiella pneumoniae sequence type 101, as previously reported from Tunisia and Spain. In all isolates, the bla(OXA-48) gene was located inside Tn1999.2 and was carried on a 60 kb plasmid with an identical RFLP pattern. The plasmid was able to conjugate from Klebsiella spp. to E. coli, and had a conjugation efficiency up to ~10000 times higher than that of pKpQIL. CONCLUSIONS: OPE, introduced mainly by medical tourism, are an emerging threat to patients from affected Mediterranean countries. The bla(OXA-48)-carrying plasmid demonstrated remarkable conjugation efficiency, which is probably important in the success of its dissemination.

Genomics and Virulence of Klebsiella pneumoniae Kpnu95 ST1412 Harboring a Novel Incf Plasmid Encoding Blactx-M-15 and Qnrs1 Causing Community Urinary Tract Infection.

The emergence of extended-spectrum ß-lactamase (ESBL)-producing multidrug resistant Klebsiella pneumoniae causing community urinary tract infections (CA-UTI) in healthy women undermines effective treatment and poses a public health concern. We performed a comprehensive genomic analysis (Illumina and MinION) and virulence studies using Caenorhabditis elegans nematodes to evaluate KpnU95, a blaCTX-M-15-producing CA-UTI K. pneumoniae strain. Whole genome sequencing identified KpnU95 as sequence type 1412 and revealed the chromosomal and plasmid-encoding resistome, virulome and persistence features. KpnU95 possess a wide virulome and caused complete C. elegans killing. The strain harbored a single novel 180.3Kb IncFIB(K) plasmid (pKpnU95), which encodes ten antibiotic resistance genes, including blaCTX-M-15 and qnrS1 alongside a wide persistome encoding heavy metal and UV resistance. Plasmid curing and reconstitution were used for loss and gain studies to evaluate its role on bacterial resistance, fitness and virulence. Plasmid curing abolished the ESBL phenotype, decreased ciprofloxacin MIC and improved bacterial fitness in artificial urine accompanied with enhanced copper tolerance, without affecting bacterial virulence. Meta-analysis supported the uniqueness of pKpnU95 and revealed plasmid-ST1412 lineage adaptation. Overall, our findings provide translational data on a CA-UTI K. pneumoniae ST1412 strain and demonstrates that ESBL-encoding plasmids play key roles in multidrug resistance and in bacterial fitness and persistence.

Assembly of cationic and amphiphilic ß-sheet FKF tripeptide confers antibacterial activity.

The race drawn against bacteria facing the evolution of antimicrobial resistance fuels research for new drugs and therapeutic strategies. FKF, a tripeptide that is cationic and amphiphilic was examined in light of its potential antimicrobial activity. Acid titration of purified peptide solution, 6% w/v (136 mM), yielded a hydrogel at pH~ 4. Cryo-TEM images of FKF revealed distinct phases formed upon increase in pH, ranging from elongated needles, uniform width fibers, sheets and tubular structures. 1H NMR attested FKF charged states as function of pH, and CD and FTIR measurements indicated that FKF ß-sheet assemblies are held by both π-π stacking and H-bonds. FKF hydrogel displayed bactericidal activity against E. coli and P. aeruginosa with a 3-log reduction in bacterial counts. The hydrogel was also found effective in reducing P. aeruginosa contamination in a skin lesion model in rats. FKF forms a unique antimicrobial peptide-hydrogel, showing neglectable effect in dissolved state, yet only when fibrillary assembled it gains functionality. STATEMENT OF SIGNIFICANCE: Ultra-short peptides are at the frontier of peptide self-assembly research. The tripeptide FKF assumes distinct assembly forms that are a function of pH, for which we have pinpointed the accompanying changes in charge. Made of natural amino acids, FKF forms a pure peptide hydrogel phase, which is intrinsically antimicrobial. We demonstrate that antimicrobial effect is only assumed by the peptide assemblies, posing self-assembly as a pre-requisite for FKF's bactericidal effect. This system provides evidence for the link between specific microscopic peptide assembled structures, macroscopic gel formation and antimicrobial effect, utilized to alleviate bacterial contamination in vivo.

Third Generation Cephalosporin Resistant Enterobacterales Infections in Hospitalized Horses and Donkeys: A Case-Case-Control Analysis.

In human medicine, infections caused by third-generation cephalosporin-resistant Enterobacterales (3GCRE) are associated with detrimental outcomes. In veterinary medicine, controlled epidemiological analyses are lacking. A matched case-case-control investigation (1:1:1 ratio) was conducted in a large veterinary hospital (2017-2019). In total, 29 infected horses and donkeys were matched to 29 animals with third-generation cephalosporin-susceptible Enterobacterales (3GCSE) infections, and 29 uninfected controls (overall n = 87). Despite multiple significant associations per bivariable analyses, the only independent predictor for 3GCRE infection was recent exposure to antibiotics (adjusted odds ratio (aOR) = 104, p < 0.001), but this was also an independent predictor for 3GCSE infection (aOR = 22, p < 0.001), though the correlation with 3GCRE was significantly stronger (aOR = 9.3, p = 0.04). In separated multivariable outcome models, 3GCRE infections were independently associated with reduced clinical cure rates (aOR = 6.84, p = 0.003) and with 90 days mortality (aOR = 3.6, p = 0.003). Klebsiella spp. were the most common 3GCRE (36%), and blaCTX-M-1 was the major ß-lactamase (79%). Polyclonality and multiple sequence types were evident among all Enterobacterales (e.g., Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae). The study substantiates the significance of 3GCRE infections in equine medicine, and their independent detrimental impact on cure rates and mortality. Multiple Enterobacterales genera, subtypes, clones and mechanisms of resistance are prevalent among horses and donkeys with 3GCRE infections.

Gut microbiota determines the social behavior of mice and induces metabolic and inflammatory changes in their adipose tissue.

The link between the gut microbiota and social behavior has been demonstrated, however the translational impact of a certain microbiota composition on stable behavioral patterns is yet to be elucidated. Here we employed an established social behavior mouse model of dominance (Dom) or submissiveness (Sub). A comprehensive 16S rRNA gene sequence analysis of Dom and Sub mice revealed a significantly different gut microbiota composition that clearly distinguishes between the two behavioral modes. Sub mice gut microbiota is significantly less diverse than that of Dom mice, and their taxa composition uniquely comprised the genera Mycoplasma and Anaeroplasma of the Tenericutes phylum, in addition to the Rikenellaceae and Clostridiaceae families. Conversely, the gut microbiota of Dom mice includes the genus Prevotella of the Bacteriodetes phylum, significantly less abundant in Sub mice. In addition, Sub mice show lower body weight from the age of 2 weeks and throughout their life span, accompanied with lower epididymis white adipose tissue (eWAT) mass and smaller adipocytes together with substantially elevated expression of inflammation and metabolic-related eWAT adipokines. Finally, fecal microbiota transplantation into germ-free mice show that Sub-transplanted mice acquired Sub microbiota and adopted their behavioral and physiological features, including depressive-like and anti-social behaviors alongside reduced eWAT mass, smaller adipocytes, and a Sub-like eWAT adipokine profile. Our findings demonstrate the critical role of the gut microbiome in determining dominance vs. submissiveness and suggest an association between gut microbiota, the eWAT metabolic and inflammatory profile, and the social behavior mode.

Transfer of carbapenem-resistant plasmid from Klebsiella pneumoniae ST258 to Escherichia coli in patient.

Klebsiella pneumoniae carbapenemase (KPC) 3-producing Escherichia coli was isolated from a carrier of KPC-3-producing K. pneumoniae. The KPC-3 plasmid was identical in isolates of both species. The patient's gut flora contained a carbapenem-susceptible E. coli strain isogenic with the KPC-3-producing isolate, which suggests horizontal interspecies plasmid transfer.

Complete nucleotide sequence of KPC-3-encoding plasmid pKpQIL in the epidemic Klebsiella pneumoniae sequence type 258.

We have determined the entire DNA sequence of plasmid pKpQIL, the bla(KPC-3)-carrying plasmid harbored by the carbapenem-resistant Klebsiella pneumoniae clone sequence type 258 (ST 258) in Israel. pKpQIL is a 113,637-bp, self-transmissible plasmid that belongs to the incompatibility group IncFII. It consists of a large backbone of a pKPN4-like plasmid and carries the bla(KPC-3)-containing Tn4401a transposon of a pNYC-like plasmid.

Carbapenem-resistant KPC-2-producing Escherichia coli in a Tel Aviv Medical Center, 2005 to 2008.

All of the carbapenem-resistant Escherichia coli (CREC) isolates identified in our hospital from 2005 to 2008 (n = 10) were studied. CREC isolates were multidrug resistant, all carried bla(KPC-2), and six of them were also extended-spectrum beta-lactamase producers. Pulsed-field gel electrophoresis indicated six genetic clones; within the same clone, similar transferable bla(KPC-2)-containing plasmids were found whereas plasmids differed between clones. Tn4401 elements were identified in all of these plasmids.