Another benefit of dietary fiber The gut microbiome can modulate the immune system and influence the therapeutic response of cancer patients, yet the mechanisms underlying the effects of microbiota are presently unclear. Spencer et al . add to our understanding of how dietary habits affect microbiota and clinical outcomes to immunotherapy. In an observational study, the researchers found that melanoma patients reporting high fiber (prebiotic) consumption had a better response to checkpoint inhibitor immunotherapy compared with those patients reporting a low-fiber diet. The most marked benefit was observed for those patients reporting a combination of high fiber consumption and no use of over-the-counter probiotic supplements. These findings provide early insights as to how diet-related factors may influence the immune response. —PNK

Enterococci are an important global cause of nosocomial infections, being increasingly associated with urinary tract infections, endocarditis, intra-abdominal and pelvic infections, catheter-related infections, surgical wound infections, and central nervous system infections. The two most common enterococci species are Enterococcus faecalis and Enterococcus faecium. Both are capable of producing biofilms, which consist of a population of cells attached irreversibly on various biotic and abiotic surfaces, encased in a hydrated matrix of exopolymeric substances. Many environmental and genetic factors are associated or have been proposed to be associated with the production of biofilm. This review discusses recent advances in knowledge about the biology and genetics of biofilm formation and the role of biofilms in enterococci pathogenesis.

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.

Endocarditis isolates of Enterococcus faecalis produced biofilm significantly more often than nonendocarditis isolates, and 39% of 79 versus 6% of 84 isolates produced strong biofilm (P < 0.0001). esp was not required, but its presence was associated with higher amounts of biofilm (P < 0.001). Mutants disrupted in dltA, efaA, ace, lsa, and six two-component regulatory systems were largely unaltered, while disruptions in epa, atn, gelE, and fsr resulted in fewer attached bacteria, as determined using phase-contrast microscopy, and less biofilm (P < 0.0001).

lines 4 and 5: "... while disruptions in epa, atn, gelE, and fsr resulted in fewer attached bacteria," should read "... while disruptions in epa (encoding enterococcal polysaccharide antigen), atn (encoding an autolysin), gelE (encoding gelatinase), and fsr (encoding the E. faecalis regulator) resulted in fewer attached bacteria." 7075

Enteroaggregative Escherichia coli (EAEC) is an emerging enteric pathogen that causes acute and chronic diarrhea among children, human immunodeficiency virus-infected patients, and travelers to developing regions of the world. The pathogenesis of EAEC strains involves the production of biofilm. In this study, we determined the association between presence of putative EAEC virulence genes and biofilm formation in 57 EAEC isolates (as defined by HEp-2 adherence) from travelers with diarrhea and in 18 EAEC isolates from travelers without diarrhea. Twelve nondiarrheagenic E. coli isolates from healthy travelers were used as controls. Biofilm formation was measured by using a microtiter plate assay with the crystal violet staining method, and the presence of the putative EAEC virulence genes aap, aatA, aggR, astA, irp2, pet, set1A, and shf was determined by PCR. EAEC isolates were more likely to produce biofilm than nondiarrheagenic E. coli isolates (P ‫؍‬ 0.027), and the production of biofilm was associated with the virulence genes aggR, set1A, aatA, and irp2, which were found in 16 (40%), 17 (43%), 10 (25%), and 27 (68%) of the biofilm producers versus only 4 (11%), 6 (6%), 2 (6%), and 15 (43%) in non-biofilm producers (P ‫؍‬ 0.008 for aggR, P ‫؍‬ 0.0004 for set1A, P ‫؍‬ 0.029 for aatA, and P ‫؍‬ 0.04 for irp2). Although the proportion of EAEC isolates producing biofilm in patients with diarrhea (51%) was similar to that in patients without diarrhea (61%), biofilm production was related to the carriage of aggR (P ‫؍‬ 0.015), set1A (P ‫؍‬ 0.001), and aatA (P ‫؍‬ 0.025). Since aggR is a master regulator of EAEC, the presence of aap (P ‫؍‬ 0.004), astA (P ‫؍‬ 0.001), irp2 (P ‫؍‬ 0.0006), pet (P ‫؍‬ 0.002), and set1A (P ‫؍‬ 0.014) in an aggR versus an aggR-lacking background was investigated and was also found to be associated with biofilm production. This study suggests that biofilm formation is a common phenomenon among EAEC isolates derived from travelers with or without diarrhea and that multiple genes associated with biofilm formation are regulated by aggR.

Minocycline-rifampin-impregnated central venous catheters (M/R CVCs) have been shown to be efficacious in reducing catheter-related bloodstream infections (CRBSI) and inhibiting the biofilm adherence of resistant Gram-positive and Gramnegative pathogens, with the exception of Pseudomonas aeruginosa and Candida spp. To expand the spectrum of antimicrobial activity, a novel second-generation M/R catheter was developed by adding chlorhexidine (CHX-M/R). CVCs and peripherally inserted central catheters (PICCs) were impregnated with CHX-M/R and compared with first-generation M/R catheters, CHXsilver sulfadiazine-treated CVCs (CHX/SS-CVCs), chlorhexidine-treated PICCs, and uncoated catheters. A biofilm catheter colonization model was used to assess the efficacy of catheters against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), P. aeruginosa, Candida albicans, and Candida glabrata. CHX-M/Rimpregnated CVCs were the only antimicrobial catheters that completely inhibited the biofilm colonization of all resistant bacterial and fungal organisms tested at all time intervals, and they were significantly superior to uncoated catheters (all P values were <0.003). Furthermore, CHX-M/R-coated CVCs had a significantly more effective and prolonged (up to 3 weeks) antimicrobial activity against MRSA and P. aeruginosa than M/R, CHX/SS, and uncoated CVCs (P < 0.0001). Similarly, CHX-M/R-coated PICCs were also superior to M/R-coated and CHX-coated PICCs in preventing biofilms of MRSA, VRE, P. aeruginosa, and Candida species (P value ‫؍‬ 0.003 for all). Our study shows that novel CHX-M/R-coated catheters have unique properties in completely inhibiting biofilm colonization of MRSA, VRE, P. aeruginosa, and fungi in a manner superior to that of M/R-and chlorhexidine-treated catheters.

Enteroaggregative Escherichia coli (EAEC) is associated with diarrhoea among travellers to developing countries. EAEC virulence properties predisposing to illness are not clear. Sixty-four EAEC strains identified by a HEp-2 cell assay and isolated from faecal samples from US and European travellers to developing countries were studied for the prevalence of 11 putative virulence genes by PCR: 49 EAEC strains from adults with acute diarrhoea and 15 EAEC strains from adults without diarrhoea. E. coli strains from the stools of healthy travellers to the same region were used as controls. EAEC carrying aggR, aap, astA and set1A were identified individually more often in the stools of subjects with diarrhoea compared with those without diarrhoea (P,0.05). EAEC isolates with two or three of these genes were associated with diarrhoea compared with EAEC isolates without the presence of these genes (P,0.05). Subjects with diarrhoea who shed EAEC isolates positive for these genes were more likely than subjects shedding EAEC negative for these genes to pass stools with gross mucus (57 vs 14 %) and faecal leukocytes (40 vs 7 %) (P,0.05). This study shows the heterogeneity of gene profiles of EAEC strains found in the stools of international travellers and suggests that the presence of aggR, aap, astA or set1A, the number of genes present and stool characteristics may be markers for more virulent EAEC strains.